Nefopam

Last updated
Nefopam
Nefopam2DACS.svg
Nefopam ball-and-stick model.png
Clinical data
Trade names nefopam medisol
AHFS/Drugs.com International Drug Names
Routes of
administration 		intramuscular, intravenous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability Low [1]
Protein binding 70–75% (mean 73%) [1] [2]
Metabolism Liver (N-demethylation, others) [1]
Metabolites Desmethylnefopam, others [1]
Elimination half-life Nefopam: 3–8 hours [1]
Desmethylnefopam: 10–15 hours [1]
Excretion Urine: 79.3% [1]
Feces: 13.4% [1]
Identifiers
  • (RS)-5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard 100.033.757 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H19NO
Molar mass 253.345 g·mol−1
3D model (JSmol)
  • CN1CCOC(C2=CC=CC=C2C1)C3=CC=CC=C3
  • InChI=1S/C17H19NO/c1-18-11-12-19-17(14-7-3-2-4-8-14)16-10-6-5-9-15(16)13-18/h2-10,17H,11-13H2,1H3 X mark.svgN
  • Key:RGPDEAGGEXEMMM-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, that is primarily used to treat moderate to severe pain. [3]

Contents

Nefopam acts in the brain and spinal cord to relieve pain via novel mechanisms: antinociceptive effects from triple monoamine reuptake inhibition, and antihyperalgesic activity through modulation of glutamatergic transmission. [4]

Medical uses

Nefopam is effective for prevention of shivering during surgery or recovery from surgery. [5] [6] Nefopam was significantly more effective than aspirin as an analgesic in one clinical trial, [7] although with a greater incidence of side effects such as sweating, dizziness and nausea, especially at higher doses. [8] [9] The estimated relative potency of nefopam to morphine indicates that 20 mg of nefopam HCl is the approximate analgesic equal of 12 mg of morphine with comparable analgesic efficacy to morphine, [10] [11] [12] or oxycodone, [13] while nefopam tends to produce fewer side effects, does not produce respiratory depression, [14] and has much less abuse potential, and so is useful either as an alternative to opioid analgesics, or as an adjunctive treatment for use alongside opioids or other types of analgesics. [12] [15] Nefopam is also used to treat severe hiccups. [16] Nefopam is also used for the manufacture of a medicament for the treatment of an affective disorder and attention-deficit disorder. [17] Nefopam can also be used as a contradiction for the treatment of Parkinson’s disease. https://www.researchgate.net/publication/228540898_Biological_Peculiarities_of_the_Analgesic_Drug_Nefopam_in_Rats

Contraindications

Nefopam is contraindicated in people with convulsive disorders, those that have received treatment with irreversible monoamine oxidase inhibitors such as phenelzine, tranylcypromine or isocarboxazid within the past 30 days and those with myocardial infarction pain, mostly due to a lack of safety data in these conditions. [18]

Side effects

Common side effects include nausea, nervousness, dry mouth, light-headedness and urinary retention. [18] Less common side effects include vomiting, blurred vision, drowsiness, sweating, insomnia, headache, confusion, hallucinations, tachycardia, aggravation of angina and rarely a temporary and benign pink discolouration of the skin or erythema multiforme. [18]

Overdose

Overdose and death have been reported with nefopam. [19] Overdose usually manifests with convulsions, hallucinations, tachycardia, and hyperdynamic circulation. [18] Treatment is usually supportive, managing cardiovascular complications with beta blockers and limiting absorption with activated charcoal. [18]

Interactions

It has additive anticholinergic and sympathomimetic effects with other agents with these properties. [18] Its use should be avoided in people receiving some types of antidepressants (tricyclic antidepressants or monoamine oxidase inhibitors) as there is the potential for serotonin syndrome or hypertensive crises to result. [18]

Pharmacology

Nefopam [20] [21]
SiteKi (nM)
SERT Tooltip Serotonin transporter29
NET Tooltip Norepinephrine transporter33
DAT Tooltip Dopamine transporter531
5-HT2A 1,685
5-HT2B 330
5-HT2C 56

Pharmacodynamics

The mechanism of action of nefopam and its analgesic effects are not well understood, although inhibition of the reuptake of serotonin, norepinephrine, and to a lesser extent dopamine (that is, acting as an SNDRI Tooltip serotonin–norepinephrine–dopamine reuptake inhibitor) is thought to be involved. [22] [4] It also reduces glutamate signaling via modulating sodium and calcium channels. [23] [4]

Pharmacokinetics

The absolute bioavailability of nefopam is low. [1] It is reported to achieve therapeutic plasma concentrations between 49 and 183 nM. [21] The drug is approximately 73% protein-bound across a plasma range of 7 to 226 ng/mL (28–892 nM). [1] The metabolism of nefopam is hepatic, by N-demethylation and via other routes. [1] Its terminal half-life is 3 to 8 hours, while that of its active metabolite, desmethylnefopam, is 10 to 15 hours. [1] It is eliminated mostly in urine, and to a lesser extent in feces. [1]

Chemistry

Nefopam is a cyclized analogue of orphenadrine, diphenhydramine, and tofenacin, with each of these compounds different from one another only by the presence of one or two carbons. [24] [25] [26] The ring system of nefopam is a benzoxazocine system. [24] [27]

Society and culture

Recreational use

Recreational use of nefopam has rarely been reported, [19] and is far less common than with opioid analgesics. [28]

Names

In the 1960s, when it was first developed, it had the generic name fenazoxine. [23]

See also

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Any member of the group of drugs used to achieve analgesia, relief from pain

An analgesic drug, also called simply an analgesic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Hydrocodone</span> Opioid drug used in pain relief

Hydrocodone, also known as dihydrocodeinone, is a semisynthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with homatropine methylbromide to relieve cough. It is also available by itself in a long-acting form under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug: in the United States a Schedule II Controlled Substance.

<span class="mw-page-title-main">Tricyclic antidepressant</span> Class of medications

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

<span class="mw-page-title-main">Tramadol</span> Medication of the opioid type, patented 1972

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).

<span class="mw-page-title-main">Hydromorphone</span> Opioid medication used for pain relief

Hydromorphone, also known as dihydromorphinone, and sold under the brand name Dilaudid among others, is a morphinan opioid used to treat moderate to severe pain. Typically, long-term use is only recommended for pain due to cancer. It may be used by mouth or by injection into a vein, muscle, or under the skin. Effects generally begin within half an hour and last for up to five hours. A 2016 Cochrane review found little difference in benefit between hydromorphone and other opioids for cancer pain.

<span class="mw-page-title-main">Duloxetine</span> Antidepressant medication used also for treatment of anxiety and chronic pain

Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, obsessive-compulsive disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth.

<span class="mw-page-title-main">Pethidine</span> Opioid analgesic

Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Otto Eisleb, its analgesic properties were first recognized by Otto Schaumann while working for IG Farben, in Germany. Pethidine is the prototype of a large family of analgesics including the pethidine 4-phenylpiperidines, the prodines, bemidones and others more distant, including diphenoxylate and analogues.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Nalbuphine</span> Opioid analgesic

Nalbuphine, sold under the brand names Nubain among others, is an opioid analgesic which is used in the treatment of pain. It is given by injection into a vein, muscle, or fat.

<span class="mw-page-title-main">Codeine</span> Opiate and prodrug of morphine used to treat pain

Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, Papaver somniferum. It is typically used to treat mild to moderate degrees of pain. Greater benefit may occur when combined with paracetamol (acetaminophen) or a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. Evidence does not support its use for acute cough suppression in children or adults. In Europe, it is not recommended as a cough medicine in those under 12 years of age. It is generally taken by mouth. It typically starts working after half an hour, with maximum effect at two hours. Its effects last for about four to six hours. Codeine exhibits abuse potential similar to other opioid medications, including a risk of habituation and overdose.

<span class="mw-page-title-main">Desmetramadol</span> Opioid painkiller medication

Desmetramadol, also known as O-desmethyltramadol (O-DSMT), is an opioid analgesic and the main active metabolite of tramadol. Tramadol is demethylated by the liver enzyme CYP2D6 to desmetramadol in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 will tend to have reduced analgesic effects from tramadol. Because desmetramadol itself does not need to be metabolized to induce an analgesic effect, it can be used in individuals with low CYP2D6 activity unlike tramadol.

<span class="mw-page-title-main">Serotonin reuptake inhibitor</span> Class of drug

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

<span class="mw-page-title-main">Tapentadol</span> Opioid analgesic of benzenoid class

Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.

<span class="mw-page-title-main">Dezocine</span> Opioid analgesic

Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.

<span class="mw-page-title-main">Proglumide</span> Chemical compound

Proglumide (Milid) is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application.

<span class="mw-page-title-main">Bicifadine</span> Chemical compound

Bicifadine (DOV-220,075) is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) discovered at American Cyanamid as an analgesic drug candidate, and licensed to DOV Pharmaceutical in 1998 after American Cyanamid was acquired by Wyeth.

An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics. Equianalgesic charts are used for calculation of an equivalent dose between different analgesics. Tables of this general type are also available for NSAIDs, benzodiazepines, depressants, stimulants, anticholinergics and others.

An analgesic adjuvant is a medication that is typically used for indications other than pain control but provides control of pain (analgesia) in some painful diseases. This is often part of multimodal analgesia, where one of the intentions is to minimize the need for opioids.

Selective norepinephrine reuptake inhibitors (sNRIs) are a class of drugs that have been marketed as antidepressants and are used for various mental disorders, mainly depression and attention-deficit hyperactivity disorder (ADHD). The norepinephrine transporter (NET) serves as the fundamental mechanism for the inactivation of noradrenergic signaling because of the NET termination in the reuptake of norepinephrine (NE). The selectivity and mechanism of action for the NRI drugs remain mostly unresolved and, to date, only a limited number of NRI-selective inhibitors are available. The first commercially available selective NRI was the drug reboxetine (Edronax), developed as a first-line therapy for major depressive disorder. Atomoxetine (Strattera) is another potent and selective NRI which is also effective and well tolerated for the treatment of ADHD in adults; it may also be a new treatment option for adults with ADHD, particularly for those patients at risk of substance abuse.

References

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  3. ↑ Brayfield A, ed. (27 October 2016). "Nefopam hydrochloride". MedicinesComplete. London, UK: Pharmaceutical Press. Retrieved 4 September 2017.
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  5. ↑ Kang P, Park SK, Yoo S, Hur M, Kim WH, Kim JT, Bahk JH (January 2019). "Comparative effectiveness of pharmacologic interventions to prevent shivering after surgery: a network meta-analysis". Minerva Anestesiologica. 85 (1): 60–70. doi:10.23736/S0375-9393.18.12813-6. PMID   30226340. S2CID   52288008.
  6. ↑ Alfonsi P, Adam F, Passard A, Guignard B, Sessler DI, Chauvin M (January 2004). "Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects". Anesthesiology. 100 (1): 37–43. doi:10.1097/00000542-200401000-00010. PMC   1283107 . PMID   14695722.
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  11. ↑ Phillips G, Vickers MD (October 1979). "Nefopam in postoperative pain". British Journal of Anaesthesia. 51 (10): 961–5. doi: 10.1093/bja/51.10.961 . PMID   391253.
  12. 1 2 Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS (April 1980). "Nefopam: a review of its pharmacological properties and therapeutic efficacy". Drugs. 19 (4): 249–67. doi:10.2165/00003495-198019040-00001. PMID   6991238. S2CID   24713213.
  13. ↑ Tigerstedt I, Tammisto T, Leander P (December 1979). "Comparison of the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain". Acta Anaesthesiologica Scandinavica. 23 (6): 555–60. doi:10.1111/j.1399-6576.1979.tb01486.x. PMID   397711. S2CID   40976610.
  14. ↑ Gasser JC, Bellville JW (August 1975). "Respiratory effects of nefopam". Clinical Pharmacology and Therapeutics. 18 (2): 175–9. doi:10.1002/cpt1975182175. PMID   1097153. S2CID   22220503.
  15. ↑ Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M (January 2005). "Nefopam and ketamine comparably enhance postoperative analgesia". Anesthesia and Analgesia. 100 (1): 169–74. doi:10.1213/01.ANE.0000138037.19757.ED. PMC   1283103 . PMID   15616073.
  16. ↑ Bilotta F, Rosa G (December 2000). "Nefopam for severe hiccups". The New England Journal of Medicine. 343 (26): 1973–4. doi: 10.1056/nejm200012283432619 . PMID   11186682.
  17. ↑ WO2007012870A2,Lyne, Michael Harvey&Bannister, Robin Mark,"Use of nefopam for the treatment of affective disorders",issued 2007-02-01
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  20. ↑ 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. Retrieved 14 August 2017.
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  22. ↑ "New Zealand Data Sheet Acupan(TM)" (PDF). Medsafe. New Zealand The Ministry of Health. 17 May 2017. Retrieved 4 September 2017.
  23. 1 2 Kim KH, Abdi S (April 2014). "Rediscovery of nefopam for the treatment of neuropathic pain". The Korean Journal of Pain. 27 (2): 103–11. doi:10.3344/kjp.2014.27.2.103. PMC   3990817 . PMID   24748937.
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  25. ↑ Sneader W (23 June 2005). Drug Discovery: A History. John Wiley & Sons. pp. 405–. ISBN   978-0-471-89979-2.
  26. ↑ Kubinyi H, Müller G (6 March 2006). Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective. John Wiley & Sons. pp. 54–. ISBN   978-3-527-60402-9.
  27. ↑ Cruz A (2014). Therapeutic Hypothermia. CRC Press. pp. 176–.
  28. ↑ Tracqui A, Berthelon L, Ludes B (May 2002). "Fatal overdosage with nefopam (Acupan)". Journal of Analytical Toxicology. 26 (4): 239–43. doi: 10.1093/jat/26.4.239 . PMID   12054367.
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