Buprenorphine

Last updated

Buprenorphine
Buprenorphine.svg
Buprenorphine molecule from xtal ball.png
Clinical data
Pronunciationbew-pre-nor-feen
Trade names Subutex, Sublocade, Belbuca, Brixadi, others
Other namesSK-2110; SK2110
AHFS/Drugs.com Monograph
MedlinePlus a605002
License data
Pregnancy
category
Dependence
liability 		Psychological: High Physical: Moderate [3]
Routes of
administration 		Sublingual, buccal, intramuscular, intravenous, transdermal, intranasal, rectal, subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Sublingual: 30% [14]
Intranasal: 48% [15]
Buccal: 65% [16] [17]
Protein binding 96%
Metabolism Liver (CYP3A4, CYP2C8)
Onset of action Within 30 min [18]
Elimination half-life 37 hours (range 20–70 hours)
Duration of action Up to 24 hrs [18]
Excretion Bile duct and kidney
Identifiers
  • (2S)-2-[(5R,6R,7R,14S)-17-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.052.664 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C29H41NO4
Molar mass 467.650 g·mol−1
3D model (JSmol)
  • Oc7ccc5c1c7O[C@H]3[C@]6(OC)[C@H](C[C@@]2([C@H](N(CC[C@@]123)CC4CC4)C5)CC6)[C@@](O)(C)C(C)(C)C
  • InChI=1S/C29H41NO4/c1-25(2,3)26(4,32)20-15-27-10-11-29(20,33-5)24-28(27)12-13-30(16-17-6-7-17)21(27)14-18-8-9-19(31)23(34-24)22(18)28/h8-9,17,20-21,24,31-32H,6-7,10-16H2,1-5H3/t20-,21-,24-,26+,27-,28+,29-/m1/s1 Yes check.svgY
  • Key:RMRJXGBAOAMLHD-IHFGGWKQSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Buprenorphine, sold under the brand name Subutex among others, is an opioid used to treat opioid use disorder, acute pain, and chronic pain. [18] It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal), or as an implant. [18] [19] For opioid use disorder, the patient must have moderate opioid withdrawal symptoms before buprenorphine can be administered under direct observation of a health-care provider. [18]

Contents

In the United States, the combination formulation of buprenorphine/naloxone (Suboxone) is usually prescribed to discourage misuse by injection. [18] However, more recently the efficacy of naloxone in preventing misuse has been brought into question, and preparations of buprenorphine combined with naloxone could potentially be less safe than buprenorphine alone. [20] Maximum pain relief is generally within an hour with effects up to 24 hours. [18] Buprenorphine affects different types of opioid receptors in different ways. [18] Depending on the type of opioid receptor, it may be an agonist, partial agonist, or antagonist. [18] Buprenorphine's activity as an agonist/antagonist is important in the treatment of opioid use disorder: it relieves withdrawal symptoms from other opioids and induces some euphoria, but also blocks the ability for many other opioids, including heroin, to cause an effect. Unlike full agonists like heroin or methadone, buprenorphine has a ceiling effect, such that taking more medicine past a certain point will not increase the effects of the drug. [21]

Side effects may include respiratory depression (decreased breathing), sleepiness, adrenal insufficiency, QT prolongation, low blood pressure, allergic reactions, constipation, and opioid addiction. [18] [22] Among those with a history of seizures, a risk exists of further seizures. [18] Opioid withdrawal following stopping buprenorphine is generally less severe than with other opioids. [18] Whether use during pregnancy is safe is unclear, but use while breastfeeding is probably safe, since the dose the infant receives is 1-2% that of the maternal dose, on a weight basis. [23] [18]

Buprenorphine was patented in 1965, and approved for medical use in the United States in 1981. [18] [24] It is on the World Health Organization's List of Essential Medicines. [25] In addition to prescription as an analgesic it is a common medication used to treat opioid use disorders, such as addiction to heroin. [26] In 2020, it was the 186th most commonly prescribed medication in the United States, with more than 2.8 million prescriptions. [27] [28] Buprenorphine may also be used recreationally for the high it can produce. [26] In the United States, buprenorphine is a schedule III controlled substance. [26]

Medical uses

Opioid use disorder

Buprenorphine patches in the pouch with packaging: A removed patch is shown on the left. In Britain, buprenorphine patches are named Butec 5, Butec 10, and so on. Butrans10mcg.jpeg
Buprenorphine patches in the pouch with packaging: A removed patch is shown on the left. In Britain, buprenorphine patches are named Butec 5, Butec 10, and so on.

Buprenorphine is used to treat people with opioid use disorder. [18] [29] : 84–7  In the U.S., the combination formulation of buprenorphine/naloxone is generally prescribed to deter injection, since naloxone, an opioid antagonist, is believed to cause acute withdrawal if the formulation is crushed and injected. [18] [30] : 99  Taken orally, the naloxone has virtually no effect, due to the drug's extremely high first-pass metabolism and low bioavailability (2%). [31] However, the efficacy of naloxone in preventing misuse by injection has as of 2020 been brought into question and preparations including naloxone could even be less safe than preparations containing solely buprenorphine. Anecdotally, posters on drug-related online forums have stated that they were able to attain a high by injecting preparations of buprenorphine despite being combined with naloxone. [20]

Before starting buprenorphine, individuals are generally advised to wait long enough after their last dose of opioid until they have some withdrawal symptoms to allow for the medication to bind the receptors, since if taken too soon, buprenorphine can displace other opioids bound to the receptors and precipitate an acute withdrawal. The dose of buprenorphine is then adjusted until symptoms improve, and individuals remain on a maintenance dose of 8–16 mg. [30] : 99–100  [32]

Because withdrawal is uncomfortable and a deterrent for many patients, users have called for different means of treatment initiation. [33] The Bernese method, also known as micro dosing was described in 2016, where very small doses of buprenorphine (0.2 to 0.5 mg) are given while patients are still using street opioids, and without precipitating withdrawal, with medicine levels slowly titrated upward. [34] This method has been used by some providers as of the 2020s. [35]

Buprenorphine versus methadone

Both buprenorphine and methadone are medications used for detoxification and opioid replacement therapy, and appear to have similar effectiveness based on limited data. [36] Both are safe for pregnant women with opioid use disorder, [30] : 101  [32] although preliminary evidence suggests that methadone is more likely to cause neonatal abstinence syndrome. [37] In the US and European Union, only designated clinics can prescribe methadone for opioid use disorder, requiring patients to travel to the clinic daily. If patients are drug-free for a period they may be permitted to receive "take-home doses," reducing their visits to as little as once a week. Alternatively, up to a month's supply of buprenorphine has been able to be prescribed by clinicians in the US or Europe who have completed basic training (8–24 hours in the US) and received a waiver/licence allowing the prescription of the medicine. [29] : 84–5  In France, buprenorphine prescription for opioid use disorder has been permitted without any special training or restrictions since 1995, resulting in treatment of approximately ten times more patients per year with buprenorphine than with methadone in the following decade. [38] In 2021, seeking to address record levels of opioid overdose, the United States also removed the requirement for a special waiver for prescribing physicians. [39] Whether this change will be sufficient to impact prescription is unclear, since even before the change as many as half of physicians with a waiver permitting them to prescribe buprenorphine did not do so, and one-third of non-waivered physicians reported that nothing would induce them to prescribe buprenorphine for opioid use disorder. [40]

Chronic pain

A transdermal patch is available for the treatment of chronic pain. [18] These patches are not indicated for use in acute pain, pain that is expected to last only for a short period, or pain after surgery, nor are they recommended for opioid addiction. [41]

Potency

For equianalgesic dosing, when used sublingually, the potency of buprenorphine is about 40 to 70 times that of morphine. [42] [43] [44] When used as a transdermal patch, the potency of buprenorphine may be 100 to 115 times that of morphine. [42] [45]

Adverse effects

Table from the 2010 ISCD study ranking various drugs (legal and illegal) based on statements by drug-harm experts. Buprenorphine was found to be the 19th overall most dangerous drug. HarmCausedByDrugsTable.svg
Table from the 2010 ISCD study ranking various drugs (legal and illegal) based on statements by drug-harm experts. Buprenorphine was found to be the 19th overall most dangerous drug.
A 2007 assessment of harm from recreational drug use (mean physical harm and mean dependence liability): Buprenorphine was ranked 9th in dependence, 8th in physical harm, and 11th in social harm. Rational scale to assess the harm of drugs (mean physical harm and mean dependence).svg
A 2007 assessment of harm from recreational drug use (mean physical harm and mean dependence liability): Buprenorphine was ranked 9th in dependence, 8th in physical harm, and 11th in social harm.

Common adverse drug reactions associated with the use of buprenorphine, similar to those of other opioids, include nausea and vomiting, drowsiness, dizziness, headache, memory loss, cognitive and neural inhibition, perspiration, itchiness, dry mouth, shrinking of the pupils of the eyes (miosis), orthostatic hypotension, male ejaculatory difficulty, decreased libido, and urinary retention. Constipation and central nervous system (CNS) effects are seen less frequently than with morphine. [48] Central sleep apnea has also been reported as a side effect of long-term buprenorphine use. [49] [50]

Respiratory effects

The most severe side effect associated with buprenorphine is respiratory depression (insufficient breathing). [18] It occurs more often in those who are also taking benzodiazepines or alcohol, or have underlying lung disease. [18] The usual reversal agents for opioids, such as naloxone, may be only partially effective, and additional efforts to support breathing may be required. [18] Respiratory depression may be less than with other opioids, particularly with chronic use. [32] In the setting of acute pain management, though, buprenorphine appears to cause the same rate of respiratory depression as other opioids such as morphine. [51] Central sleep apnea is possible with long-term use, possibly resolving with dose reduction. [49] [50]

Buprenorphine dependence

Buprenorphine treatment carries the risk of causing psychological or physiological (physical) dependencies. It has a slow onset of activity, with a long duration of action, and a long half-life of 24 to 60 hours. Once a patient has stabilised on the (buprenorphine) medication and programme, three options remain - continual use (buprenorphine-only medication), switching to a buprenorphine/naloxone combination, or a medically supervised withdrawal. [32]

Pain management

Achieving acute opioid analgesia is difficult in persons using buprenorphine for pain management. [52] However, a systematic review found no clear benefit to bridging or stopping buprenorphine when used in opioid substitution therapy to facilitate perioperative pain management, but failure to restart it was found to pose concerns for relapse. Therefore, it is recommended that buprenorphine opioid substitution therapy is continued in the perioperative period when possible. In addition, preoperative pain management in patients taking buprenorphine should use an interdisciplinary approach with multimodal analgesia. [53]

Pharmacology

Pharmacodynamics

Buprenorphine [54]
SiteKi (nM)ActionSpeciesStimulationRef
MOR Tooltip μ-Opioid receptor0.2157
0.081		Partial agonistHuman
Monkey		38%±10 [55] [56] [57]
[58]
DOR Tooltip δ-Opioid receptor2.9–6.1
0.82		AntagonistHuman
Monkey		0 [55] [57] [59]
[58]
KOR Tooltip κ-Opioid receptor0.62–2.5
0.44		Antagonist/weak partial agonist (dose and source dependent)Human
Monkey		9%±5 [55] [57] [59]
[58]
NOP Tooltip Nociceptin receptor77.4Partial agonistHuman50±10

(8mg≥)

 [56] [57] [59]
σ1 >100,000NDND [60]
σ2 NDNDNDND
NMDA Tooltip N-Methyl-D-aspartate receptorNDNDNDND
TLR4 Tooltip Toll-like receptor 4>10,000AgonistHuman [61]
SERT Tooltip Serotonin transporter>100,000NDRat [62]
NET Tooltip Norepinephrine transporter>100,000NDRat [62]
DAT Tooltip Dopamine transporterNDNDNDND
VGSC Tooltip Voltage-gated sodium channel33,000 (IC50)InhibitorRodent [63]
Values are Ki (nM), unless otherwise noted. The smaller
the value, the more strongly the drug binds to the site.

Opioid receptor modulator

Buprenorphine has been reported to possess these following pharmacological activities: [57]

  • μ-Opioid receptor (MOR): Very high affinity partial agonist: [64] at low doses, the MOR-mediated effects of buprenorphine are comparable to those of other narcotics, but these effects reach a "ceiling" as the receptor population is saturated. [59] This behavior is responsible for several unique properties: buprenorphine greatly reduces the effect of most other MOR agonists, [65] can cause precipitated withdrawal when used in actively opioid dependent persons, [65] and has a lower incidence of respiratory depression and fatal overdose relative to full MOR agonists. [66]
  • κ-Opioid receptor (KOR): High affinity antagonist/weak partial agonist [64] —this activity is hypothesized to underlie some of the effects of buprenorphine on mood disorders and addiction. [67] [68] [69]
  • δ-Opioid receptor (DOR): High affinity antagonist [64] [70]
  • Nociceptin receptor (NOP, ORL-1): Weak affinity, very weak partial agonist [64]

In simplified terms, buprenorphine can essentially be thought of as a nonselective, mixed agonist–antagonist opioid receptor modulator, [71] acting as an unusually high affinity, weak partial agonist of the MOR, a high affinity antagonist of the KOR and DOR, and a relatively low affinity, very weak partial agonist of the ORL-1/NOP. [59] [72] [65] [73] [74] [75]

Although buprenorphine is a partial agonist of the MOR, human studies have found that it acts like a full agonist with respect to analgesia in opioid-intolerant individuals. [76] Conversely, buprenorphine behaves like a partial agonist of the MOR with respect to respiratory depression. [76]

Buprenorphine is also known to bind to with high affinity and antagonize the putative ε-opioid receptor. [77] [78]

Full analgesic efficacy of buprenorphine requires both exon 11- [79] and exon 1-associated μ-opioid receptor splice variants. [80]

The active metabolites of buprenorphine are not thought to be clinically important in its CNS effects. [76]

In positron emission tomography (PET) imaging studies, buprenorphine was found to decrease whole-brain MOR availability due to receptor occupancy by 41% (i.e., 59% availability) at 2 mg, 80% (i.e., 20% availability) at 16 mg, and 84% (i.e., 16% availability) at 32 mg. [81] [82] [83] [84]

Other actions

Unlike some other opioids and opioid antagonists, buprenorphine binds only weakly to and possesses little if any activity at the sigma receptor. [85] [86]

Buprenorphine also blocks voltage-gated sodium channels via the local anesthetic binding site, and this underlies its potent local anesthetic properties. [63]

Similarly to various other opioids, buprenorphine has also been found to act as an agonist of the toll-like receptor 4, albeit with very low affinity. [61]

Pharmacokinetics

Buprenorphine is metabolized by the liver, via CYP3A4 (also CYP2C8 seems to be involved) isozymes of the cytochrome P450 enzyme system, into norbuprenorphine (by N-dealkylation). The glucuronidation of buprenorphine is primarily carried out by UGT1A1 and UGT2B7, and that of norbuprenorphine by UGT1A1 and UGT1A3. These glucuronides are then eliminated mainly through excretion into bile. The elimination half-life of buprenorphine is 20 to 73 hours (mean 37 hours). Due to the mainly hepatic elimination, no risk of accumulation exists in people with renal impairment. [87]

One of the major active metabolites of buprenorphine is norbuprenorphine, which, in contrast to buprenorphine itself, is a full agonist of the MOR, DOR, and ORL-1, and a partial agonist at the KOR. [88] [89] However, relative to buprenorphine, norbuprenorphine has extremely little antinociceptive potency (1/50th that of buprenorphine), but markedly depresses respiration (10-fold more than buprenorphine). [90] This may be explained by very poor brain penetration of norbuprenorphine due to a high affinity of the compound for P-glycoprotein. [90] In contrast to norbuprenorphine, buprenorphine and its glucuronide metabolites are negligibly transported by P-glycoprotein. [90]

The glucuronides of buprenorphine and norbuprenorphine are also biologically active, and represent major active metabolites of buprenorphine. [91] Buprenorphine-3-glucuronide has affinity for the MOR (Ki = 4.9 pM), DOR (Ki = 270 nM) and ORL-1 (Ki = 36 μM), and no affinity for the KOR. It has a small antinociceptive effect and no effect on respiration. Norbuprenorphine-3-glucuronide has no affinity for the MOR or DOR, but does bind to the KOR (Ki = 300 nM) and ORL-1 (Ki = 18 μM). It has a sedative effect but no effect on respiration.

Chemistry

Buprenorphine is a semisynthetic derivative of thebaine, [92] and is fairly soluble in water, as its hydrochloride salt. [93] It degrades in the presence of light. [93]

Detection in body fluids

Buprenorphine and norbuprenorphine may be quantified in blood or urine to monitor use or non-medical recreational use, confirm a diagnosis of poisoning, or assist in a medicolegal investigation. A significant overlap of drug concentrations exists in body fluids within the possible spectrum of physiological reactions ranging from asymptomatic to comatose. Therefore, knowing both the route of administration of the drug and the level of tolerance to opioids of the individual is critical when results are interpreted. [94]

History

In 1969, researchers at Reckitt and Colman (now Reckitt Benckiser) had spent 10 years attempting to synthesize an opioid compound "with structures substantially more complex than morphine [that] could retain the desirable actions whilst shedding the undesirable side effects". Physical dependence and withdrawal from buprenorphine itself remain important issues since buprenorphine is a long-acting opioid. [95] Reckitt found success when researchers synthesized RX6029 which had shown success in reducing dependence in test animals. RX6029 was named buprenorphine and began trials on humans in 1971. [96] [97] By 1978, buprenorphine was first launched in the UK as an injection to treat severe pain, with a sublingual formulation released in 1982.

Society and culture

Regulation

United States

In the United States, buprenorphine and buprenorphine with naloxone were approved for opioid use disorder by the Food and Drug Administration in October 2002. [98] The DEA rescheduled buprenorphine from a schedule V drug to a schedule III drug just before approval. [99] The ACSCN for buprenorphine is 9064, and being a schedule III substance, it does not have an annual manufacturing quota imposed by the DEA. [100] The salt in use is the hydrochloride, which has a free-base conversion ratio of 0.928.

In the years before buprenorphine/naloxone was approved, Reckitt Benckiser had lobbied Congress to help craft the Drug Addiction Treatment Act of 2000, which gave authority to the Secretary of Health and Human Services to grant a waiver to physicians with certain training to prescribe and administer schedule III, IV, or V narcotic drugs for the treatment of addiction or detoxification. Before this law was passed, such treatment was permitted only in clinics designed specifically for drug addiction. [101]

The waiver, which can be granted after the completion of an eight-hour course, was required for outpatient treatment of opioid addiction with buprenorphine from 2000 to 2021. Initially, the number of people each approved physician could treat was limited to 10. This was eventually modified to allow approved physicians to treat up to 100 people with buprenorphine for opioid addiction in an outpatient setting. [102] This limit was increased by the Obama administration, raising the number of patients to which doctors can prescribe to 275. [103] On 14 January 2021, the US Department of Health and Human Services announced that the waiver would no longer be required to prescribe buprenorphine to treat up to 30 people concurrently. [104]

New Jersey authorized paramedics to give buprenorphine to people at the scene after they have recovered from an overdose. [105]

Europe

In the European Union, Subutex and Suboxone, buprenorphine's high-dose sublingual tablet preparations, were approved for opioid use disorder treatment in September 2006. [106] In the Netherlands, buprenorphine is a list II drug of the Opium Law, though special rules and guidelines apply to its prescription and dispensation. In France, buprenorphine prescription by general practitioners and dispensed by pharmacies has been permitted since the mid-1990s as a response to HIV and overdose risk. Deaths caused by heroin overdose were reduced by four-fifths between 1994 and 2002, and the incidence of AIDS among people who inject drugs in France fell from 25% in the mid-1990s to 6% in 2010. [107]

Barriers to access

In the US, the list price for a long-acting injectable form is five to 20 times as much as a daily pill. [108] This has reduced the number of people who are able to get a single monthly dose, instead of daily pills. [108] Some jails consider the more expensive form a positive tradeoff: a single monthly injection may be simpler and easier for the staff to manage than daily trips to the dispensary to have a nurse provide a pill and make sure that it has been swallowed. [108]

Brand names

Buprenorphine is available under the brand names Cizdol, Brixadi (approved in the US by FDA for addiction treatment in 2023), Suboxone (with naloxone), Subutex (typically used for opioid use disorder), Zubsolv, Bunavail, Buvidal (approved in the UK, Europe and Australia for addiction treatment in 2018), Sublocade (approved in the US in 2018), [109] [110] [111] Probuphine, Temgesic (sublingual tablets for moderate to severe pain), Buprenex (solutions for injection often used for acute pain in primary-care settings), Norspan, and Butrans (transdermal preparations used for chronic pain). [93] In Poland buprenorphine is available under the trade names Bunondol (for pain treatment, when morphine is too little; amounts of 0.2mg and 0.4mg) and Bunorfin (for addicts substitution in amount of 2 and 8mg).

Research

Microdosing

There is some evidence that a buprenorphine microdosing regime, started before opioid withdrawal symptoms have started, can be effective in helping people transition away from opioid dependence. [112]

Depression

Some evidence supports the use of buprenorphine for depression. [113] Buprenorphine/samidorphan, a combination product of buprenorphine and samidorphan (a preferential μ-opioid receptor antagonist), appears useful for treatment-resistant depression. [114]

A buprenorphine implant (developmental code name SK-2110) is under development by Shenzhen ScienCare Pharmaceutical in China for the treatment of refractory major depressive disorder. [115] [116]

Cocaine dependence

In combination with samidorphan or naltrexone (μ-opioid receptor antagonists), buprenorphine is under investigation for the treatment of cocaine dependence, and recently demonstrated effectiveness for this indication in a large-scale (n = 302) clinical trial (at a high buprenorphine dose of 16 mg, but not a low dose of 4 mg). [117] [118]

Neonatal abstinence

Buprenorphine has been used in the treatment of the neonatal abstinence syndrome, [119] a condition in which newborns exposed to opioids during pregnancy demonstrate signs of withdrawal. [120] In the United States, use currently is limited to infants enrolled in a clinical trial conducted under an FDA-approved investigational new drug (IND) application. [121] Preliminary research suggests that buprenorphine is associated with shorter time in hospital for neonates, compared to methadone. [122] An ethanolic formulation used in neonates is stable at room temperature for at least 30 days. [123]

Veterinary uses

Veterinarians administer buprenorphine for perioperative pain, particularly in cats, where its effects are similar to morphine. The drug's legal status and lower potential for human abuse makes it an attractive alternative to other opioids. [124]

It has veterinary medical use for treatment of pain in dogs and cats, as well as other animals. [125] [126] [127]

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An opiate is an alkaloid substance derived from opium. It differs from the similar term opioid in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum. The psychoactive compounds found in the opium plant include morphine, codeine, and thebaine. Opiates have long been used for a variety of medical conditions, with evidence of opiate trade and use for pain relief as early as the eighth century AD. Most opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America.

<span class="mw-page-title-main">(+)-Naloxone</span> Drug

(+)-Naloxone (dextro-naloxone) is a drug which is the opposite enantiomer of the opioid antagonist drug (−)-naloxone. Unlike (−)-naloxone, (+)-naloxone has no significant affinity for opioid receptors, but instead has been discovered to act as a selective antagonist of Toll-like receptor 4. This receptor is involved in immune system responses, and activation of TLR4 induces glial activation and release of inflammatory mediators such as TNF-α and Interleukin-1.

<span class="mw-page-title-main">Buprenorphine/samidorphan</span> Combination drug formulation

Buprenorphine/samidorphan is a combination formulation of buprenorphine and samidorphan which is under development as an add on to antidepressants in treatment-resistant depression (TRD).

A receptor modulator, or receptor ligand, is a general term for a substance, endogenous or exogenous, that binds to and regulates the activity of chemical receptors. They are ligands that can act on different parts of receptors and regulate activity in a positive, negative, or neutral direction with varying degrees of efficacy. Categories of these modulators include receptor agonists and receptor antagonists, as well as receptor partial agonists, inverse agonists, orthosteric modulators, and allosteric modulators, Examples of receptor modulators in modern medicine include CFTR modulators, selective androgen receptor modulators (SARMs), and muscarinic ACh receptor modulators.

<span class="mw-page-title-main">Buprenorphine/naloxone</span> Opioid treatment

Buprenorphine/naloxone, sold under the brand name Suboxone among others, is a fixed-dose combination medication that includes buprenorphine and naloxone. It is used to treat opioid use disorder, and reduces the mortality of opioid use disorder by 50%. It relieves cravings to use and withdrawal symptoms. Buprenorphine/­naloxone is available for use in two different forms, under the tongue or in the cheek.

Buprenorphine/naltrexone is an experimental combination drug formulation of buprenorphine, a μ-opioid receptor (MOR) weak partial agonist and κ-opioid receptor (KOR) antagonist, and naltrexone, a MOR and KOR silent antagonist, which is under investigation for the potential treatment of psychiatric disorders. The combination of the two drugs is thought to result in a selective blockade of the KOR and hence fewer MOR activation-related concerns such as euphoria and opioid dependence. It has been found to produce antidepressant-like effects in mice and has recently been found to be effective in the treatment of cocaine dependence in a large clinical trial.

<span class="mw-page-title-main">Opioid withdrawal</span> Withdrawal symptoms of opiates

Opioid withdrawal is a set of symptoms arising from the sudden cessation or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs syndrome, nausea, vomiting, diarrhea, sweating, and an elevated heart rate. Opioid use triggers a rapid adaptation in cellular signaling pathways that, when reduced or stopped, can cause adverse physiological effects. All opioids, both recreational drugs and medications, when reduced or stopped, can lead to opioid withdrawal symptoms. When withdrawal symptoms are due to recreational opioid use, the term opioid use disorder is used, whereas when due to prescribed medications, the term prescription opioid use disorder is used. Opioid withdrawal can be managed by the use of opioid replacement therapy, while symptoms may be relieved by the use of medications such as lofexidine and clonidine.

Opioid agonist therapy (OAT) is a treatment in which prescribed opioid agonists are given to patients who live with Opioid use disorder (OUD). In the case of methadone maintenance treatment (MMT), methadone is used to treat dependence on heroin or other opioids, and is administered on an ongoing basis.

<span class="mw-page-title-main">Methocinnamox</span> Opioid antagonist

Methocinnamox (MCAM) is an opioid receptor antagonist. It is a pseudo-irreversible non-competitive antagonist of the μ-opioid receptor and a competitive antagonist of the κ- and δ-opioid receptors. The drug has a very long duration of action of up to months with a single dose due to its pseudo-irreversibility. It is administered in animals by intravenous or subcutaneous injection.

References

  1. ↑ "Buprenorphine Use During Pregnancy". Drugs.com. 14 October 2019. Archived from the original on 10 November 2020. Retrieved 17 May 2020.
  2. 1 2 Australian Public Assessment Report for Buprenorphine (PDF) (Report). Therapeutic Goods Administration. November 2019. Archived (PDF) from the original on 20 March 2024.
  3. ↑ Bonewit-West K, Hunt AS, Applegate E (2012). Today's Medical Assistant: Clinical and Administrative Procedures. Elsevier Health Sciences. p. 571. ISBN   9781455701506. Archived from the original on 10 January 2023. Retrieved 16 February 2020.
  4. ↑ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  5. ↑ "ARCHIVED - Report Stakeholder Workshop on a National Buprenorphine Program". Health Canada . 6 December 2004. Archived from the original on 26 March 2020. Retrieved 10 January 2020.
  6. ↑ "Neurological therapies". Health Canada . 9 May 2018. Retrieved 13 April 2024.
  7. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  8. ↑ "Subutex (buprenorphine sublingual tablets), CIII Initial U.S. Approval: 1981". DailyMed. Archived from the original on 27 May 2023. Retrieved 26 May 2023.
  9. ↑ "Sublocade- buprenorphine solution". DailyMed. 15 March 2023. Archived from the original on 27 May 2023. Retrieved 26 May 2023.
  10. ↑ "Butrans- buprenorphine patch, extended release". DailyMed. 26 June 2022. Archived from the original on 27 May 2023. Retrieved 26 May 2023.
  11. ↑ "Brixadi- buprenorphine injection". DailyMed. 21 June 2023. Archived from the original on 26 June 2023. Retrieved 25 June 2023.
  12. ↑ "FDA Approves New Buprenorphine Treatment Option for Opioid Use Disorder". U.S. Food and Drug Administration (Press release). 23 May 2023. Retrieved 26 May 2023.
  13. ↑ "Buvidal EPAR". European Medicines Agency (EMA). 20 November 2018. Retrieved 10 August 2024.
  14. ↑ Mendelson J, Upton RA, Everhart ET, Jacob P, Jones RT (January 1997). "Bioavailability of sublingual buprenorphine". Journal of Clinical Pharmacology. 37 (1): 31–37. doi:10.1177/009127009703700106. PMID   9048270. S2CID   31735116.
  15. ↑ Eriksen J, Jensen NH, Kamp-Jensen M, Bjarnø H, Friis P, Brewster D (November 1989). "The systemic availability of buprenorphine administered by nasal spray". The Journal of Pharmacy and Pharmacology. 41 (11): 803–805. doi:10.1111/j.2042-7158.1989.tb06374.x. PMID   2576057. S2CID   1286222.
  16. ↑ "Buprenorphine / Naloxone Buccal Film (BUNAVAIL) C-III" (PDF). Pharmacy Benefits Management (PBM) Services. September 2014. Archived (PDF) from the original on 20 October 2020. Retrieved 10 February 2020.
  17. ↑ "Bunavail (buprenorphine and naloxone buccal film), CIII Initial U.S. Approval: 2002". DailyMed. Archived from the original on 27 May 2023. Retrieved 26 May 2023.
  18. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 "Buprenorphine Hydrochloride". drugs.com. American Society of Health-System Pharmacists. 26 January 2017. Archived from the original on 18 July 2017. Retrieved 17 March 2017.
  19. ↑ "FDA approves first buprenorphine implant for treatment of opioid dependence". U.S. Food and Drug Administration (Press release). 26 May 2016. Archived from the original on 30 November 2017. Retrieved 12 December 2017.
  20. 1 2 Blazes CK, Morrow JD (11 September 2020). "Reconsidering the Usefulness of Adding Naloxone to Buprenorphine". Frontiers in Psychiatry. 11: 549272. doi: 10.3389/fpsyt.2020.549272 . PMC   7517938 . PMID   33061915.
  21. ↑ Whelan PJ, Remski K (January 2012). "Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds". Journal of Neurosciences in Rural Practice. 3 (1): 45–50. doi: 10.4103/0976-3147.91934 . PMC   3271614 . PMID   22346191.
  22. ↑ "Buprenorphine". The Substance Abuse and Mental Health Services Administration. 15 June 2015. Archived from the original on 26 August 2020. Retrieved 14 October 2020.
  23. ↑ "Buprenorphine use while Breastfeeding". Drugs.com. Archived from the original on 10 November 2020. Retrieved 7 February 2021.
  24. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 528. ISBN   9783527607495. Archived from the original on 10 January 2023. Retrieved 29 May 2020.
  25. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  26. 1 2 3 "Buprenorphine". SAMHSA Center for Substance Abuse Treatment (CSAT). July 2019. Archived from the original on 20 August 2020. Retrieved 9 January 2020.
  27. ↑ "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 7 October 2022.
  28. ↑ "Buprenorphine - Drug Usage Statistics". ClinCalc. Archived from the original on 11 October 2022. Retrieved 7 October 2022.
  29. 1 2 Levounis P, Avery J (2018). "Patient Assessment". In Renner Jr JA, Levounis P, LaRose AT (eds.). Office-based buprenorphine treatment of opioid use disorder. Arlington, VA: American Psychiatric Association Publishing. ISBN   978-1-61537-170-9. OCLC   1002302926.
  30. 1 2 3 Restrepo R, Levounis P (2018). "Clinical Use of Buprenorphine". In Renner Jr JA, Levounis P, LaRose AT (eds.). Office-based buprenorphine treatment of opioid use disorder. Arlington, VA: American Psychiatric Association Publishing. ISBN   978-1-61537-170-9. OCLC   1002302926.
  31. ↑ "Naloxone Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 2 January 2015. Retrieved 2 January 2015.
  32. 1 2 3 4 "Buprenorphine". www.samhsa.gov. 31 May 2016. Archived from the original on 9 July 2021. Retrieved 3 December 2017.
  33. ↑ Sue KL, Cohen S, Tilley J, Yocheved A (January 2022). "A Plea From People Who Use Drugs to Clinicians: New Ways to Initiate Buprenorphine Are Urgently Needed in the Fentanyl Era". Journal of Addiction Medicine. 16 (4): 389–391. doi:10.1097/ADM.0000000000000952. PMID   35020693. S2CID   245925947.
  34. ↑ Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, et al. (20 July 2016). "Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method". Substance Abuse and Rehabilitation. 7: 99–105. doi: 10.2147/SAR.S109919 . PMC   4959756 . PMID   27499655.
  35. ↑ Ahmed S, Bhivandkar S, Lonergan BB, Suzuki J (July 2021). "Microinduction of Buprenorphine/Naloxone: A Review of the Literature". The American Journal on Addictions. 30 (4): 305–315. doi:10.1111/ajad.13135. PMID   33378137. S2CID   229721826.
  36. ↑ Gowing L, Ali R, White JM, Mbewe D (February 2017). "Buprenorphine for managing opioid withdrawal". The Cochrane Database of Systematic Reviews. 2017 (2): CD002025. doi:10.1002/14651858.CD002025.pub5. PMC   6464315 . PMID   28220474.
  37. ↑ Lemon LS, Caritis SN, Venkataramanan R, Platt RW, Bodnar LM (March 2018). "Methadone Versus Buprenorphine for Opioid Use Dependence and Risk of Neonatal Abstinence Syndrome". Epidemiology. 29 (2): 261–268. doi:10.1097/EDE.0000000000000780. PMC   5792296 . PMID   29112519. Methadone is associated with increased risk of neonatal abstinence syndrome compared with buprenorphine in infants exposed in utero. This association is subject to minimal bias due to unmeasured confounding by severity of addiction.
  38. ↑ Auriacombe M, Fatséas M, Dubernet J, Daulouède JP, Tignol J (2004). "French field experience with buprenorphine". The American Journal on Addictions. 13 (Suppl 1): S17–S28. doi:10.1080/10550490490440780. PMID   15204673.
  39. ↑ Office of the Assistant Secretary for Health (OASH) (14 January 2021). "HHS Expands Access to Treatment for Opioid Use Disorder". HHS.gov. Archived from the original on 25 January 2022. Retrieved 5 January 2022.
  40. ↑ Stringfellow EJ, Humphreys K, Jalali MS (2021). "Removing The X-Waiver Is One Small Step Toward Increasing Treatment Of Opioid Use Disorder, But Great Leaps Are Needed". Health Affairs Forefront. doi:10.1377/forefront.20210419.311749. Archived from the original on 14 October 2022. Retrieved 5 January 2022.
  41. ↑ "Butrans Medication Guide". Butrans Medication Guide. Purdue Pharma L.P. Archived from the original on 14 July 2014. Retrieved 7 July 2014.
  42. 1 2 Cote J, Montgomery L (July 2014). "Sublingual buprenorphine as an analgesic in chronic pain: a systematic review". Pain Medicine. 15 (7): 1171–1178. doi: 10.1111/pme.12386 . PMID   24995716.
  43. ↑ "Drug Enforcement Administration (2005). "Ch. 4 Narcotics: Narcotics Treatment Drugs: Buprenorphine". Drugs of Abuse. U.S. Department of Justice. Archived from the original on 2 November 2006.
  44. ↑ "Opioid Conversion Guide" (PDF). Department of Health, Government of Western Australia. February 2016. Archived (PDF) from the original on 18 April 2020. Retrieved 10 February 2020.
  45. ↑ Khanna IK, Pillarisetti S (2015). "Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain". Journal of Pain Research. 8: 859–870. doi: 10.2147/JPR.S85951 . PMC   4675640 . PMID   26672499.
  46. ↑ Nutt DJ, King LA, Phillips LD (November 2010). "Drug harms in the UK: a multicriteria decision analysis". Lancet. 376 (9752): 1558–1565. CiteSeerX   10.1.1.690.1283 . doi:10.1016/S0140-6736(10)61462-6. PMID   21036393. S2CID   5667719.
  47. ↑ Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet. 369 (9566): 1047–1053. doi:10.1016/S0140-6736(07)60464-4. PMID   17382831. S2CID   5903121.
  48. ↑ Budd K, Raffa RB. (eds.) Buprenorphine – The unique opioid analgesic. Thieme, 200, ISBN   3-13-134211-0
  49. 1 2 Tchikrizov V, Richert AC, Bhardwaj SB (1 July 2022). "Case of buprenorphine-associated central sleep apnea resolving with dose reduction". Journal of Opioid Management. 18 (4): 391–394. doi:10.5055/jom.2022.0732. PMID   36052936. S2CID   251959885.
  50. 1 2 DeVido J, Connery H, Hill KP (1 July 2015). "Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series". Journal of Opioid Management. 11 (4): 363–366. doi:10.5055/jom.2015.0285. PMC   4754775 . PMID   26312963.
  51. ↑ White LD, Hodge A, Vlok R, Hurtado G, Eastern K, Melhuish TM (April 2018). "Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials". British Journal of Anaesthesia. 120 (4): 668–678. doi: 10.1016/j.bja.2017.11.086 . PMID   29576108.
  52. ↑ Alford DP, Compton P, Samet JH (January 2006). "Acute pain management for patients receiving maintenance methadone or buprenorphine therapy". Annals of Internal Medicine. 144 (2): 127–134. doi:10.7326/0003-4819-144-2-200601170-00010. PMC   1892816 . PMID   16418412.
  53. ↑ Disha Mehta, Vinod Thomas, Jacinta Johnson, Brooke Scott, Sandra Cortina, Landon Berger. 2020 Continuation of Buprenorphine to Facilitate Postoperative Pain Management for Patients on Buprenorphine Opioid Agonist Therapy. 23;E163-E174. https://www.painphysicianjournal.com/current/pdf?article=NzAzMQ%3D%3D&journal=125 Archived 18 May 2023 at the Wayback Machine
  54. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 29 August 2021. Retrieved 14 August 2017.
  55. 1 2 3 Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, et al. (March 1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications". NIDA Research Monograph. 178: 440–466. PMID   9686407.
  56. 1 2 Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L (December 2009). "Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists". The Journal of Pharmacology and Experimental Therapeutics. 331 (3): 946–953. doi:10.1124/jpet.109.156711. PMC   2784721 . PMID   19713488.
  57. 1 2 3 4 5 Khroyan TV, Wu J, Polgar WE, Cami-Kobeci G, Fotaki N, Husbands SM, et al. (January 2015). "BU08073 a buprenorphine analogue with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice". British Journal of Pharmacology. 172 (2): 668–680. doi:10.1111/bph.12796. PMC   4292977 . PMID   24903063.
  58. 1 2 3 Negus SS, Bidlack JM, Mello NK, Furness MS, Rice KC, Brandt MR (November 2002). "Delta opioid antagonist effects of buprenorphine in rhesus monkeys". Behavioural Pharmacology. 13 (7): 557–570. doi:10.1097/00008877-200211000-00005. PMID   12409994.
  59. 1 2 3 4 5 Lutfy K, Cowan A (October 2004). "Buprenorphine: a unique drug with complex pharmacology". Current Neuropharmacology. 2 (4): 395–402. doi:10.2174/1570159043359477. PMC   2581407 . PMID   18997874.
  60. ↑ Freye E (1987). "Interaction of Mixed Agonist-Antagonists with Different Receptor Sites Using Nalbuphine as a Model Substance". Opioid Agonists, Antagonists and Mixed Narcotic Analgesics. pp. 67–78. doi:10.1007/978-3-642-71854-0_6. ISBN   978-3-540-17471-4.
  61. 1 2 Hutchinson MR, Zhang Y, Shridhar M, Evans JH, Buchanan MM, Zhao TX, et al. (January 2010). "Evidence that opioids may have toll-like receptor 4 and MD-2 effects". Brain, Behavior, and Immunity. 24 (1): 83–95. doi:10.1016/j.bbi.2009.08.004. PMC   2788078 . PMID   19679181.
  62. 1 2 Codd EE, Shank RP, Schupsky JJ, Raffa RB (September 1995). "Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception". The Journal of Pharmacology and Experimental Therapeutics. 274 (3): 1263–1270. PMID   7562497.
  63. 1 2 Leffler A, Frank G, Kistner K, Niedermirtl F, Koppert W, Reeh PW, et al. (June 2012). "Local anesthetic-like inhibition of voltage-gated Na(+) channels by the partial μ-opioid receptor agonist buprenorphine". Anesthesiology. 116 (6): 1335–1346. doi: 10.1097/ALN.0b013e3182557917 . PMID   22504149.
  64. 1 2 3 4 Gudin J, Fudin J (June 2020). "A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain". Pain and Therapy. 9 (1): 41–54. doi:10.1007/s40122-019-00143-6. PMC   7203271 . PMID   31994020.
  65. 1 2 3 Robinson SE (2002). "Buprenorphine: an analgesic with an expanding role in the treatment of opioid addiction". CNS Drug Reviews. 8 (4): 377–390. doi:10.1111/j.1527-3458.2002.tb00235.x. PMC   6741692 . PMID   12481193.
  66. ↑ Khanna IK, Pillarisetti S (2015). "Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain". Journal of Pain Research. 8: 859–870. doi: 10.2147/JPR.S85951 . PMC   4675640 . PMID   26672499.
  67. ↑ Madison CA, Eitan S (April 2020). "Buprenorphine: prospective novel therapy for depression and PTSD". Psychological Medicine. 50 (6): 881–893. doi:10.1017/S0033291720000525. PMID   32204739. S2CID   214630021.
  68. ↑ Stefanowski B, Antosik-Wójcińska A, Święcicki Ł (April 2020). "The use of buprenorphine in the treatment of drug-resistant depression - an overview of the studies". Psychiatria Polska. 54 (2): 199–207. doi: 10.12740/PP/102658 . PMID   32772054.
  69. ↑ Carlezon WA, Béguin C, Knoll AT, Cohen BM (September 2009). "Kappa-opioid ligands in the study and treatment of mood disorders". Pharmacology & Therapeutics. 123 (3): 334–343. doi:10.1016/j.pharmthera.2009.05.008. PMC   2740476 . PMID   19497337.
  70. ↑ Benzon H, Raja S, Fishman S, Liu SS, Cohen SP (2017). Essentials of Pain Medicine E-Book. Elsevier Health Sciences. p. 382. ISBN   9780323445412. Archived from the original on 14 January 2023. Retrieved 29 May 2020.
  71. ↑ Jacob JJ, Michaud GM, Tremblay EC (1979). "Mixed agonist-antagonist opiates and physical dependence". British Journal of Clinical Pharmacology. 7 (Suppl 3): 291S–296S. doi:10.1111/j.1365-2125.1979.tb04703.x. PMC   1429306 . PMID   572694.
  72. ↑ Kress HG (March 2009). "Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine". European Journal of Pain. 13 (3): 219–230. doi:10.1016/j.ejpain.2008.04.011. PMID   18567516. S2CID   8243410.
  73. ↑ Ruiz P, Strain EC (2011). Lowinson and Ruiz's Substance Abuse: A Comprehensive Textbook. Lippincott Williams & Wilkins. p. 439. ISBN   978-1-60547-277-5. Archived from the original on 14 January 2023. Retrieved 14 March 2016.
  74. ↑ Bidlack JM (2014). "Mixed Kappa/Mu Partial Opioid Agonists as Potential Treatments for Cocaine Dependence". Mixed κ/μ partial opioid agonists as potential treatments for cocaine dependence. Advances in Pharmacology. Vol. 69. pp. 387–418. doi:10.1016/B978-0-12-420118-7.00010-X. ISBN   9780124201187. PMID   24484983.
  75. ↑ Ehrich E, Turncliff R, Du Y, Leigh-Pemberton R, Fernandez E, Jones R, et al. (May 2015). "Evaluation of opioid modulation in major depressive disorder". Neuropsychopharmacology. 40 (6): 1448–1455. doi:10.1038/npp.2014.330. PMC   4397403 . PMID   25518754.
  76. 1 2 3 Coller JK, Christrup LL, Somogyi AA (February 2009). "Role of active metabolites in the use of opioids". European Journal of Clinical Pharmacology. 65 (2): 121–139. doi:10.1007/s00228-008-0570-y. PMID   18958460. S2CID   9977741.
  77. ↑ Mizoguchi H, Wu HE, Narita M, Hall FS, Sora I, Uhl GR, et al. (2002). "Antagonistic property of buprenorphine for putative epsilon-opioid receptor-mediated G-protein activation by beta-endorphin in pons/medulla of the mu-opioid receptor knockout mouse". Neuroscience. 115 (3): 715–721. doi:10.1016/s0306-4522(02)00486-4. PMID   12435410. S2CID   54316989.
  78. ↑ Mizoguchi H, Spaulding A, Leitermann R, Wu HE, Nagase H, Tseng LF (July 2003). "Buprenorphine blocks epsilon- and micro-opioid receptor-mediated antinociception in the mouse". The Journal of Pharmacology and Experimental Therapeutics. 306 (1): 394–400. doi:10.1124/jpet.103.048835. PMID   12721333. S2CID   44036890.
  79. ↑ Xu J, Xu M, Hurd YL, Pasternak GW, Pan YX (February 2009). "Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene". Journal of Neurochemistry. 108 (4): 962–972. doi:10.1111/j.1471-4159.2008.05833.x. PMC   2727151 . PMID   19077058.
  80. ↑ Grinnell S et al. (2014): Buprenorphine analgesia requires exon 11-associated mu opioid receptor splice variants. The FASEB Journal
  81. ↑ Colasanti A, Lingford-Hughes A, Nutt D (2013). "Opioids Neuroimaging". In Miller PM (ed.). Biological Research on Addiction. Comprehensive Addictive Behaviors and Disorders. Vol. 2. Elsevier. pp. 675–687. doi:10.1016/B978-0-12-398335-0.00066-2. ISBN   9780123983350.
  82. ↑ Zubieta J, Greenwald MK, Lombardi U, Woods JH, Kilbourn MR, Jewett DM, et al. (September 2000). "Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study". Neuropsychopharmacology. 23 (3): 326–334. doi: 10.1016/S0893-133X(00)00110-X . PMID   10942856. S2CID   27350905.
  83. ↑ Greenwald MK, Johanson CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA, et al. (November 2003). "Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers". Neuropsychopharmacology. 28 (11): 2000–2009. doi: 10.1038/sj.npp.1300251 . PMID   12902992. S2CID   20773085.
  84. ↑ Greenwald M, Johanson CE, Bueller J, Chang Y, Moody DE, Kilbourn M, et al. (January 2007). "Buprenorphine duration of action: mu-opioid receptor availability and pharmacokinetic and behavioral indices". Biological Psychiatry. 61 (1): 101–110. doi:10.1016/j.biopsych.2006.04.043. PMID   16950210. S2CID   46105421.
  85. ↑ Doweiko HE (14 March 2014). Concepts of Chemical Dependency. Cengage Learning. pp. 149–. ISBN   978-1-285-45717-8.
  86. ↑ USP DI. United States Pharmacopeial Convention. 1997. ISBN   9780913595947.
  87. ↑ Moody DE, Fang WB, Lin SN, Weyant DM, Strom SC, Omiecinski CJ (December 2009). "Effect of rifampin and nelfinavir on the metabolism of methadone and buprenorphine in primary cultures of human hepatocytes". Drug Metabolism and Disposition. 37 (12): 2323–2329. doi:10.1124/dmd.109.028605. PMC   2784702 . PMID   19773542.
  88. ↑ Yassen A, Kan J, Olofsen E, Suidgeest E, Dahan A, Danhof M (May 2007). "Pharmacokinetic-pharmacodynamic modeling of the respiratory depressant effect of norbuprenorphine in rats". The Journal of Pharmacology and Experimental Therapeutics. 321 (2): 598–607. doi:10.1124/jpet.106.115972. PMID   17283225. S2CID   11921738.
  89. ↑ Huang P, Kehner GB, Cowan A, Liu-Chen LY (May 2001). "Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist". The Journal of Pharmacology and Experimental Therapeutics. 297 (2): 688–695. PMID   11303059.
  90. 1 2 3 Brown SM, Campbell SD, Crafford A, Regina KJ, Holtzman MJ, Kharasch ED (October 2012). "P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception". The Journal of Pharmacology and Experimental Therapeutics. 343 (1): 53–61. doi:10.1124/jpet.112.193433. PMC   3464040 . PMID   22739506.
  91. ↑ Brown SM, Holtzman M, Kim T, Kharasch ED (December 2011). "Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active". Anesthesiology. 115 (6): 1251–1260. doi:10.1097/ALN.0b013e318238fea0. PMC   3560935 . PMID   22037640.
  92. ↑ Heel RC, Brogden RN, Speight TM, Avery GS (February 1979). "Buprenorphine: a review of its pharmacological properties and therapeutic efficacy". Drugs. 17 (2): 81–110. doi:10.2165/00003495-197917020-00001. PMID   378645. S2CID   19577410.
  93. 1 2 3 "Buprenorphine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. 14 January 2014. Archived from the original on 28 August 2021. Retrieved 6 April 2014.
  94. ↑ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 190–192. ISBN   978-0962652370.
  95. ↑ "IMPORTANT SAFETY INFORMATION". Archived from the original on 18 March 2019. Retrieved 25 June 2016.
  96. ↑ Campbell ND, Lovell AM (February 2012). "The history of the development of buprenorphine as an addiction therapeutic". Annals of the New York Academy of Sciences. 1248 (1): 124–139. Bibcode:2012NYASA1248..124C. doi:10.1111/j.1749-6632.2011.06352.x. PMID   22256949. S2CID   28395410.
  97. ↑ Louis S. Harris, ed. (1998). Problems of Drug Dependence, 1998: Proceedings of the 66th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc (PDF). NIDA Research Monograph 179. Archived from the original (PDF) on 3 December 2016. Retrieved 5 August 2012.
  98. ↑ McCormick CG (8 October 2002). "Subutex and Suboxone Approval Letter]" (PDF). Letter to Reckitt Benckiser. U.S. Food and Drug Administration.
  99. ↑ 67 FR 62354, 7 October 2002
  100. ↑ "Quotas – Conversion Factors for Controlled Substances". Deadiversion.usdoj.gov. Archived from the original on 2 March 2016. Retrieved 7 November 2016.
  101. ↑ "Drug Addiction Treatment Act of 2000". SAMHSA, U.S. Department of Health & Human Services. Archived from the original on 4 March 2013.
  102. ↑ "The National Alliance of Advocates for Buprenorphine Treatment". naabt.org. Archived from the original on 12 November 2020. Retrieved 19 May 2013.
  103. ↑ "Obama administration's change on buprenorphine policy". Business Insider. 6 July 2016. Archived from the original on 18 March 2020. Retrieved 7 November 2016.
  104. ↑ "HHS Expands Access to Treatment for Opioid Use Disorder". US Deptartment of Health and Human Services (Press release). 14 January 2021. Archived from the original on 14 January 2021. Retrieved 14 January 2021.
  105. ↑ "In national first, N.J. program will let paramedics administer buprenorphine". STAT. 26 June 2019. Archived from the original on 3 October 2019. Retrieved 21 November 2019.
  106. ↑ "Suboxone EU Approval". Ema.europa.eu. Archived from the original on 24 December 2016. Retrieved 7 November 2016.
  107. ↑ Poloméni P, Schwan R (3 March 2014). "Management of opioid addiction with buprenorphine: French history and current management". International Journal of General Medicine. 7: 143–148. doi: 10.2147/IJGM.S53170 . PMC   3949694 . PMID   24623988.
  108. 1 2 3 Hoffman J (9 September 2024). "How a Maine County Jail Helped Prisoners Blunt Opioid Cravings". The New York Times . But for all its potential, Sublocade, approved in 2017, is not widely used in treatment settings outside of prisons either. The chief barrier is cost. A monthly injection of Sublocade has a list price of about $2,000. A month's supply of the pills lists from about $90 to $360, depending on the dose.
  109. ↑ "FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for opioid use disorder". U.S. Food and Drug Administration (Press release). 30 November 2017. Archived from the original on 3 December 2017. Retrieved 5 December 2017.
  110. ↑ "Indivior drug to fight opioid addiction approved by U.S. FDA". Reuters. 2017. Archived from the original on 5 December 2017. Retrieved 5 December 2017.
  111. ↑ "Sublocade Now Available for Moderate-to-Severe Opioid Use Disorder". MPR. 1 March 2018. Archived from the original on 23 September 2019. Retrieved 23 September 2019.
  112. ↑ Ahmed S, Bhivandkar S, Lonergan BB, Suzuki J (July 2021). "Microinduction of Buprenorphine/Naloxone: A Review of the Literature". Am J Addict (Review). 30 (4): 305–315. doi:10.1111/ajad.13135. PMID   33378137. S2CID   229721826.
  113. ↑ Stanciu CN, Glass OM, Penders TM (April 2017). "Use of Buprenorphine in treatment of refractory depression-A review of current literature". Asian Journal of Psychiatry. 26: 94–98. doi:10.1016/j.ajp.2017.01.015. PMID   28483102.
  114. ↑ Ragguett RM, Rong C, Rosenblat JD, Ho RC, McIntyre RS (April 2018). "Pharmacodynamic and pharmacokinetic evaluation of buprenorphine + samidorphan for the treatment of major depressive disorder". Expert Opinion on Drug Metabolism & Toxicology. 14 (4): 475–482. doi:10.1080/17425255.2018.1459564. PMID   29621905. S2CID   4633923.
  115. ↑ "SK 2110". AdisInsight. 25 August 2023. Retrieved 27 September 2024.
  116. ↑ "8741810.PDF" (PDF). Retrieved 7 August 2024. [SK2110 - Buprenorphine implant for the treatment of major depressive disorder SK2110 is an implant of buprenorphine hydrochloride for patients with major depression and refractory depression who cannot be relieved by taking at least two drugs. Buprenorphine hydrochloride was developed by Indivior and is a KOR1 antagonist and MOR1 agonist. Currently, the highest development stage of the drug is approval for marketing, which is used to treat opioid dependence, chronic pain, pain and substance-related disorders. The company changes the route of administration to prepare an implant, which can reduce the frequency of administration, improve the bioavailability of the drug, improve patient compliance, and maintain a stable blood drug concentration, thereby reducing adverse drug reactions. At the same time, the implanted administration method can also play a role in avoiding drug abuse. At present, the project is conducting laboratory preparation small-scale trial prescription process exploration and preliminary pharmacodynamic studies. SK2110 can take effect quickly and quickly relieve patients' depressive symptoms. It is expected to submit an IND application to my country's drug regulatory authorities in 2024.]
  117. ↑ Ling W, Hillhouse MP, Saxon AJ, Mooney LJ, Thomas CM, Ang A, et al. (August 2016). "Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study". Addiction. 111 (8): 1416–1427. doi:10.1111/add.13375. PMC   4940267 . PMID   26948856.
  118. ↑ "Alkermes Presents Positive Clinical Data of ALKS 5461 at 52nd Annual New Clinical Drug Evaluation Unit Meeting". Reuters. 2012. Archived from the original on 24 September 2015. Retrieved 30 June 2017.
  119. ↑ Kraft WK, Gibson E, Dysart K, Damle VS, Larusso JL, Greenspan JS, et al. (September 2008). "Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial". Pediatrics. 122 (3): e601–e607. doi:10.1542/peds.2008-0571. PMC   2574639 . PMID   18694901.
  120. ↑ Kraft WK, van den Anker JN (October 2012). "Pharmacologic management of the opioid neonatal abstinence syndrome". Pediatric Clinics of North America. 59 (5): 1147–1165. doi:10.1016/j.pcl.2012.07.006. PMC   4709246 . PMID   23036249.
  121. ↑ Clinical trial number NCT00521248 for "Buprenorphine for the Treatment of Neonatal Abstinence Syndrome" at ClinicalTrials.gov
  122. ↑ Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ (July 2017). "Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women". Pharmacotherapy. 37 (7): 824–839. doi:10.1002/phar.1958. PMID   28543191. S2CID   13772333. Currently, methadone and buprenorphine are both widely used as the backbone of MAT [medication-assisted treatment]. The distinguishing outcomes in studies among these two opioid agonists are that infants exposed to buprenorphine in clinical trials required shorter treatment duration, less medication to treat the NAS symptoms and experienced shorter hospitalizations compared to infants exposed to methadone. A caveat to these findings is that some of the supporting data were based on using buprenorphine in combination with naloxone instead of buprenorphine as a single agent.
  123. ↑ Anagnostis EA, Sadaka RE, Sailor LA, Moody DE, Dysart KC, Kraft WK (October 2011). "Formulation of buprenorphine for sublingual use in neonates". The Journal of Pediatric Pharmacology and Therapeutics. 16 (4): 281–284. doi:10.5863/1551-6776-16.4.281. PMC   3385042 . PMID   22768012.
  124. ↑ Martinez M (May 2014). "Options in perioperative analgesia: buprenorphine v. methadone". Veterinary Practice. Archived from the original on 19 January 2022. Retrieved 19 January 2022.
  125. ↑ Claude A (June 2015). "Buprenorphine" (PDF). cliniciansbrief.com. Archived from the original (PDF) on 16 May 2017. Retrieved 25 February 2017.
  126. ↑ Kukanich B, Papich MG (14 May 2013). "Opioid Analgesic Drugs". In Riviere JE, Papich MG (eds.). Veterinary Pharmacology and Therapeutics (9th ed.). John Wiley & Sons. pp. 323–325. ISBN   9781118685907. Archived from the original on 1 May 2023. Retrieved 25 December 2021.
  127. ↑ Steagall PV, Ruel HL, Yasuda T, Monteiro BP, Watanabe R, Evangelista MC, et al. (May 2020). "Pharmacokinetics and analgesic effects of intravenous, intramuscular or subcutaneous buprenorphine in dogs undergoing ovariohysterectomy: a randomized, prospective, masked, clinical trial". BMC Veterinary Research. 16 (1): 154. doi: 10.1186/s12917-020-02364-w . PMC   7245774 . PMID   32448336.
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