Nalmefene

Last updated

Nalmefene
Nalmefene.svg
Clinical data
Trade names Revex, others
Other namesNalmetrene; 6-Desoxy-6-methylenenaltrexone; CPH-101; JF-1; Lu AA36143; NIH-10365; ORF-11676
AHFS/Drugs.com Monograph
MedlinePlus a605043
License data
Routes of
administration 		By mouth, intranasal, intramuscular, intravenous, subcutaneous
Drug class Opioid antagonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 40–50% (orally) [7]
Protein binding 45%
Metabolism Liver
Elimination half-life 10.8 ± 5.2 hours
Excretion Kidney
Identifiers
  • 17-Cyclopropylmethyl-4,5α-epoxy-6-methylenemorphinan-3,14-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.164.948 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H25NO3
Molar mass 339.435 g·mol−1
3D model (JSmol)
  • OC(C1=C2[C@@]34[C@H]5O1)=CC=C2C[C@@H](N(CC4)CC6CC6)[C@]3(O)CCC5=C
  • InChI=1S/C21H25NO3/c1-12-6-7-21(24)16-10-14-4-5-15(23)18-17(14)20(21,19(12)25-18)8-9-22(16)11-13-2-3-13/h4-5,13,16,19,23-24H,1-3,6-11H2/t16-,19+,20+,21-/m1/s1 Yes check.svgY
  • Key:WJBLNOPPDWQMCH-MBPVOVBZSA-N Yes check.svgY
   (verify)

Nalmefene, sold under the brand name Revex among others, is a medication that is used in the treatment of opioid overdose and alcohol dependence. [2] [3] Nalmefene belongs to the class of opioid antagonists and can be taken by mouth, administered by injection, or delivered through nasal administration. [8]

Contents

In terms of its chemical structure and biological activity, nalmefene is similar to another opioid antagonist called naltrexone, as they are both derivatives of opiates. However, nalmefene offers certain advantages over naltrexone. These include a longer elimination half-life, which means it stays in the body for a longer duration, improved absorption when taken by mouth, and no observed liver toxicity that is dependent on the dosage. [9]

Nalmefene is available as a generic medication. [10]

Medical uses

Opioid overdose

Intravenous doses of nalmefene have been shown effective at counteracting the respiratory depression produced by opioid overdose. [3]

Alcohol dependence

Nalmefene is used in the European Union to reduce alcohol dependence [2] and NICE recommends the use of nalmefene to reduce alcohol consumption in combination with psychological support for people who drink heavily. [11]

Based on a meta analysis, the usefulness of nalmefene for alcohol dependence is unclear. [12] Nalmefene, in combination with psychosocial management, may decrease the amount of alcohol drunk by people who are alcohol dependent. [12] [13] The medication may also be taken "as needed", when a person feels the urge to consume alcohol. [13]

Side effects

Very common

The following side effects of nalmefene are very common (≥10% incidence):

Common

The following side effects of nalmefene are common (≥1% to <10% incidence):

The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration. [14]

Pharmacology

Pharmacodynamics

Opioid receptor blockade

Nalmefene at human opioid receptors
Affinities (Ki Tooltip Inhibitor constant)RatiosRefs
MOR Tooltip μ-Opioid receptor KOR Tooltip κ-Opioid receptor DOR Tooltip δ-Opioid receptorMOR:KOR:DOR
0.24 nM0.083 nM16 nM3:1:193 [15] [16]
0.3 nM0.3 nM7.3 nM1:1:24 [17] [18]

Nalmefene acts as an inverse agonist of the μ-opioid receptor (MOR) (Ki Tooltip Inhibitor constant = 0.24 nM) and as a weak partial agonist (Ki = 0.083 nM; Emax = 20–30%) of the κ-opioid receptor (KOR), with similar binding for these two receptors but a several-fold preference for the KOR. [15] [16] In another study however, nalmefene had approximately equal affinity for the MOR and KOR. [17] [18] In vivo evidence indicative of KOR activation, such as elevation of serum prolactin levels due to dopamine suppression and increased hypothalamic–pituitary–adrenal axis activation via enhanced adrenocorticotropic hormone and cortisol secretion, has been observed in humans and animals. [15] [19] Side effects typical of KOR activation such as hallucinations and dissociation have also been observed with nalmefene in human studies. [20] It is thought that nalmefene activation of KOR may produce dysphoria and anxiety. [21] In addition to MOR and KOR binding, nalmefene also possesses some, albeit far lower affinity for the δ-opioid receptor (DOR) (Ki = 16 nM), where it behaves as an antagonist. [15] [16] [22]

Nalmefene is structurally related to naltrexone and differs from it by substitution of the ketone group at the C6 position of naltrexone with a methylene group (CH2). It binds to the MOR with similar affinity relative to naltrexone, but binds "somewhat more avidly" to the KOR and DOR in comparison. [15] [19]

Nalmefene with a single 1 mg dose by intravenous injection has been found to produce brain MOR blockade of 99% at 5 minutes, 90% at 2 hours, 33% at 4 hours, and 10% at 8 hours. [23] A lower dose of 1 μg/kg intravenously resulted in brain MOR blockade of 52% at 5 minutes, 33% at 2 hours, 47% at 4 hours, and 26% at 8 hours. [23] With oral administration, peak brain MOR occupancy of 87 to 100% was found after 3 hours with single or repeated dosing of nalmefene. [24] [25] At 26 hours (1.1 days) post-administration, brain MOR occupancy was 83 to 100%; at 50 hours (2.1 days), it was 48 to 72%; and at 74 hours (3.1 days), it was 12 to 46%. [24] [25] The half-time of nalmefene occupancy of brain MORs is about 29 hours and is much longer than with naloxone. [24] [26] Substantial brain MOR occupancy occurs with nalmefene even when blood levels of nalmefene are very low. [24] [25] The prolonged brain MOR occupancy of nalmefene may be due to slow dissociation of nalmefene from MORs consequent to its high MOR affinity. [24] [25]

Metabolism

Nalmefene is extensively metabolized in the liver, mainly by conjugation with glucuronic acid and also by N-dealkylation. Less than 5% of the dose is excreted unchanged. The glucuronide metabolite is entirely inactive, while the N-dealkylated metabolite has minimal pharmacological activity.[ citation needed ]

Chemistry

Nalmefene is a derivative of naltrexone and was first reported in 1975. [27]

Society and culture

Nalmefene was first reported in a patent in 1974. [28]

United States

In the United States, immediate-release injectable nalmefene was approved in 1995, as an antidote for opioid overdose. [29] It was sold under the brand name Revex. [3] The product was discontinued by its manufacturer around 2008. [30] [31] [32] A generic version was approved for medical use in the United States in February 2022. [10] [33]

In May 2023, the Food and Drug Administration (FDA) approved a nalmefene hydrochloride nasal spray, under the brand name Opvee, for the emergency treatment of opioid overdose in people aged twelve years of age and older. [34]

In August 2024, the FDA approved a nalmefene hydrochloride auto-injector (Zurnai) for the emergency treatment of known or suspected opioid overdose in people aged twelve years of age and older. [5] [35] The FDA granted the application for the nalmefene hydrochloride auto-injector fast track and priority review designations. [35] The FDA granted approval of Zurnai to Purdue Pharma L.P. [35]

As of 2012, nalmefene in pill form, used for the treatment of alcohol dependence and other addictive behaviors, is not available in the United States. [9]

European Union

Danish pharmaceutical company Lundbeck has licensed nalmefene from Biotie Therapies and performed clinical trials with nalmefene for treatment of alcohol dependence. [36] In 2011, they submitted an application for their medication named Selincro to the European Medicines Agency. [37] The medication was authorized for use in the EU in March 2013. [38] and in October 2013, Scotland became the first country in the EU to prescribe the drug for alcohol dependence. [39] England followed Scotland by offering the medication as a treatment for problem drinking in October 2014. [40] In November 2014, nalmefene was approved as a possible treatment supplied by Britain's National Health Service (NHS) for reducing alcohol consumption in people with alcohol dependence. [41]

Research

Oral nalmefene was under development for the treatment of pathological gambling, interstitial cystitis, pruritus, rheumatoid arthritis, shock, and smoking withdrawal, but development was discontinued for all of these indications. [42] Formulations of nalmefene for use by intramuscular injection, intravenous injection, and intranasal administration are in late-stage development for the treatment of opioid-related disorders. [43] [44]

Nalmefene might be useful to treat cocaine addiction. [45]

Related Research Articles

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References

  1. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  2. 1 2 3 "Selincro 18mg film-coated tablets". UK Electronic Medicines Compendium. September 2016. Archived from the original on 27 April 2021. Retrieved 13 June 2017.
  3. 1 2 3 4 "Revex- nalmefene hydrochloride injection, solution". DailyMed. Archived from the original on 21 January 2022. Retrieved 11 February 2022.
  4. ↑ "Opvee- nalmefene hydrochloride spray". DailyMed. 19 June 2023. Archived from the original on 8 August 2024. Retrieved 25 June 2023.
  5. 1 2 https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218590s000lbl.pdf
  6. ↑ "Selincro EPAR". European Medicines Agency. 13 March 2013. Archived from the original on 11 February 2022. Retrieved 11 February 2022.
  7. ↑ Kyhl LE, Li S, Faerch KU, Soegaard B, Larsen F, Areberg J (February 2016). "Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy". British Journal of Clinical Pharmacology. 81 (2). Wiley: 290–300. doi:10.1111/bcp.12805. PMC   4833148 . PMID   26483076.
  8. ↑ "FDA Approves Prescription Nasal Spray to Reverse Opioid Overdose". U.S. Food and Drug Administration (FDA) (Press release). 23 May 2023. Archived from the original on 1 June 2023. Retrieved 1 June 2023.
  9. 1 2 "Nalmefene". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Library of Medicine. 24 March 2020. PMID   31643618. Bookshelf ID: NBK548295. Archived from the original on 13 November 2021. Retrieved 12 February 2022.
  10. 1 2 "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 11 February 2022. Archived from the original on 12 February 2022. Retrieved 11 February 2022.
  11. ↑ "Technology appraisal guidance [TA325]: Nalmefene for reducing alcohol consumption in people with alcohol dependence". NICE. 26 November 2014. Archived from the original on 27 March 2021. Retrieved 13 June 2017.
  12. 1 2 Palpacuer C, Laviolle B, Boussageon R, Reymann JM, Bellissant E, Naudet F (December 2015). "Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials". PLOS Medicine. 12 (12): e1001924. doi: 10.1371/journal.pmed.1001924 . PMC   4687857 . PMID   26694529.
  13. 1 2 Paille F, Martini H (2014). "Nalmefene: a new approach to the treatment of alcohol dependence". Substance Abuse and Rehabilitation. 5 (5): 87–94. doi: 10.2147/sar.s45666 . PMC   4133028 . PMID   25187751.
  14. ↑ "Selincro". European Medicines Agency. Archived from the original on 24 October 2015. Retrieved 3 November 2015.
  15. 1 2 3 4 5 Bart G, Schluger JH, Borg L, Ho A, Bidlack JM, Kreek MJ (December 2005). "Nalmefene induced elevation in serum prolactin in normal human volunteers: partial kappa opioid agonist activity?". Neuropsychopharmacology. 30 (12): 2254–62. doi: 10.1038/sj.npp.1300811 . PMID   15988468.
  16. 1 2 3 Linda P. Dwoskin (29 January 2014). Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Elsevier Science. pp. 398–. ISBN   978-0-12-420177-4. Archived from the original on 10 January 2023. Retrieved 31 October 2016.
  17. 1 2 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 Res Monogr. 178: 440–66. PMID   9686407.
  18. 1 2 Clark SD, Abi-Dargham A (October 2019). "The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence". Biol Psychiatry. 86 (7): 502–511. doi: 10.1016/j.biopsych.2019.05.012 . PMID   31376930. S2CID   162168648.
  19. 1 2 Niciu MJ, Arias AJ (October 2013). "Targeted opioid receptor antagonists in the treatment of alcohol use disorders". CNS Drugs. 27 (10): 777–87. doi:10.1007/s40263-013-0096-4. PMC   4600601 . PMID   23881605.
  20. ↑ "Nalmefene. Alcohol dependence: no advance". Prescrire International. 23 (150): 150–2. June 2014. PMID   25121147. Archived from the original on 28 October 2021. Retrieved 28 April 2016. (subscription required)
  21. ↑ Stahl SM (15 May 2014). Prescriber's guide: Stahl's essential psychopharmacology. Cambridge University Press. pp. 465–. ISBN   978-1-139-95300-9. Archived from the original on 10 January 2023. Retrieved 31 October 2016.
  22. ↑ Grosshans M, Mutschler J, Kiefer F (July 2015). "Treatment of cocaine craving with as-needed nalmefene, a partial κ opioid receptor agonist: first clinical experience". International Clinical Psychopharmacology. 30 (4): 237–8. doi:10.1097/YIC.0000000000000069. PMID   25647453.
  23. 1 2 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.
  24. 1 2 3 4 5 Soyka M, Rösner S (November 2010). "Nalmefene for treatment of alcohol dependence". Expert Opin Investig Drugs. 19 (11): 1451–9. doi:10.1517/13543784.2010.522990. PMID   20868291. S2CID   9227860.
  25. 1 2 3 4 Ingman K, Hagelberg N, Aalto S, Någren K, Juhakoski A, Karhuvaara S, et al. (December 2005). "Prolonged central mu-opioid receptor occupancy after single and repeated nalmefene dosing". Neuropsychopharmacology. 30 (12): 2245–53. doi: 10.1038/sj.npp.1300790 . PMID   15956985. S2CID   2453226.
  26. ↑ Kim S, Wagner HN, Villemagne VL, Kao PF, Dannals RF, Ravert HT, et al. (November 1997). "Longer occupancy of opioid receptors by nalmefene compared to naloxone as measured in vivo by a dual-detector system". J Nucl Med. 38 (11): 1726–31. PMID   9374341.
  27. ↑ Fulton BS (2014). Drug Discovery for the Treatment of Addiction: Medicinal Chemistry Strategies. John Wiley & Sons. p. 341. ISBN   9781118889572. Archived from the original on 10 January 2023. Retrieved 13 June 2017.
  28. ↑ U.S. patent 3,814,768
  29. ↑ "Nalmefene label" (PDF). U.S. Food and Drug Administration. Archived (PDF) from the original on 12 February 2022. Retrieved 12 February 2022.
  30. ↑ "Baxter discontinues Revex injection". Monthly Prescribing Reference website. Haymarket Media, Inc. 9 July 2008. Archived from the original on 11 October 2016. Retrieved 10 October 2016.
  31. ↑ "Drug Shortages". U.S. Food and Drug Administration (FDA). Archived from the original on 26 December 2008.
  32. ↑ "Determination That Revex (Nalmefene Hydrochloride Injection), 0.1 Milligram Base/Milliliter and 1.0 Milligram Base/Milliliter, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness". Federal Register. 3 November 2017. Archived from the original on 28 January 2022. Retrieved 11 February 2022.
  33. ↑ "Nalmefene hydrochloride: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 12 February 2022. Retrieved 11 February 2022.
  34. ↑ "FDA Approves Prescription Nasal Spray to Reverse Opioid Overdose". U.S. Food and Drug Administration (FDA) (Press release). 23 May 2023. Archived from the original on 1 June 2023. Retrieved 1 June 2023.
  35. 1 2 3 "FDA Approves First Nalmefene Hydrochloride Auto-Injector to Reverse Opioid Overdose". U.S. Food and Drug Administration (Press release). 7 August 2024. Retrieved 8 August 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  36. ↑ Clinical trial number NCT00811720 for "Efficacy of nalmefene in patients with alcohol dependence (ESENSE1" at ClinicalTrials.gov
  37. ↑ "Lundbeck submits Selincro in EU; Novo Nordisk files Degludec in Japan". The Pharma Letter. 22 December 2011. Archived from the original on 23 June 2012. Retrieved 5 March 2012.
  38. ↑ "Selincro". European Medicines Agency. 13 March 2013. Archived from the original on 4 September 2018. Retrieved 4 October 2014.
  39. ↑ "Alcohol cravings drug nalmefene granted approval in Scotland". BBC News. 7 October 2013. Archived from the original on 28 April 2021. Retrieved 21 June 2018.
  40. ↑ "Nalmefene granted approval in England" . The Independent. 3 October 2014. Archived from the original on 18 June 2022.
  41. ↑ "Alcohol dependence treatment accepted for NHS use". MIMS. 26 November 2014. Archived from the original on 28 April 2021. Retrieved 13 June 2017.
  42. ↑ "Nalmefene oral - Acorda Therapeutics/Lundbeck A/S". AdisInsight. Springer Nature Switzerland AG. Archived from the original on 1 November 2021. Retrieved 1 November 2021.
  43. ↑ "Nalmefene hydrochloride injection - Purdue Pharma". AdisInsight. Springer Nature Switzerland AG. Archived from the original on 7 November 2021. Retrieved 1 November 2021.
  44. ↑ "Intranasal nalmefene - Opiant Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG. Archived from the original on 2 November 2021. Retrieved 1 November 2021.
  45. ↑ 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. Elsevier. pp. 387–418. doi:10.1016/B978-0-12-420118-7.00010-X. ISBN   9780124201187. PMID   24484983.
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