Nalmefene

Nalmefene
Nalmefene
Systematic (IUPAC) name
17-cyclopropylmethyl-4,5α-epoxy-6-methylenemorphinan-3,14-diol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a605043
Pregnancy cat.  ?
Legal status Prescription Only Medicine
Routes Oral, Intravenous
Pharmacokinetic data
Protein binding 45%
Metabolism hepatic
Half-life 10.8 ± 5.2 hours
Excretion renal
Identifiers
CAS number 55096-26-9 YesY
58895-64-0 (HCl)
ATC code None
PubChem CID 5284594
ChemSpider 4447642 YesY
UNII TOV02TDP9I N
ChEMBL CHEMBL982 N
Chemical data
Formula C21H25NO3 
Mol. mass 375.9 g/mol (hydrochloride)
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Nalmefene (Revex) is an opioid receptor antagonist developed in the early 1970s,[1] and used primarily in the management of alcohol dependence, and also has been investigated for the treatment of other addictions such as pathological gambling and addiction to shopping.

Nalmefene is an opiate derivative similar in both structure and activity to the opiate antagonist naltrexone. Advantages of nalmefene relative to naltrexone include longer half-life, greater oral bioavailability and no observed dose-dependent liver toxicity. As with other drugs of this type, nalmefene can precipitate acute withdrawal symptoms in patients who are dependent on opioid drugs, or more rarely when used post-operatively to counteract the effects of strong opioids used in surgery.

Nalmefene differs from naltrexone by substitution of the ketone group at the 6-position of naltrexone with a methylene (CH2) group, which considerably increases binding affinity to the μ-opioid receptor. Nalmefene also has high affinity for the other opioid receptors, and is known as a "universal antagonist" for its ability to block all three.

In clinical trials using this drug, doses used for treating alcoholism were in the range of 20-80 mg per day, orally. [2] The doses tested for treating pathological gambling were between 25-100 mg per day. [3] In both trials, there was little difference in efficacy between the lower and higher dosage regimes, and the lower dose (20 and 25 mg, respectively) was the best tolerated, with similar therapeutic efficacy to the higher doses and less side effects. Nalmefene is thus around twice as potent as naltrexone when used for the treatment of addictions.

Intravenous doses of nalmefene at between 0.5 to 1 milligram have been shown effective at counteracting the respiratory depression produced by opiate overdose [4], although this is not the usual application for this drug as naloxone is less expensive.

Doses of nalmefene greater than 1.5 mg do not appear to give any greater benefit in this application. Nalmefene's longer half-life might however make it useful for treating overdose involving longer acting opioids such as methadone, as it would require less frequent dosing and hence reduce the likelihood of renarcotization as the antagonist wears off.

Nalmefene is extensively metabolised 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.

Side effects

Properties

  • Soluble in water up to 130mg/mL, soluble in chloroform up to 0.13 mg/mL
  • pKa 7.6
  • Distribution half-life: 41 minutes

References

  1. ^ US patent 3814768, Jack Fishman et al, "6-METHYLENE-6-DESOXY DIHYDRO MORPHINE AND CODEINE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS", published 1971-11-26, issued 1974-06-04 
  2. ^ Arch Gen Psychiatry - Abstract: A Double-blind, Placebo-Controlled Study of Oral Nalmefene for Alcohol Dependence, August 1999, Mason et al. 56 (8): 719
  3. ^ Clinical Trial Of Nalmefene In The Treatment Of Pathological Gambling
  4. ^ http://www.fda.gov/cder/foi/label/2000/20459S2lbl.pdf
  5. ^ Nalmefene Hydrochloride Drug Information, Professional

Wikimedia Foundation. 2010.

Игры ⚽ Нужно сделать НИР?

Look at other dictionaries:

  • nalmefene — nal·me·fene (nălʹmə fēn ) n. A drug, C21H25NO3, used as an antagonist to narcotic drugs.   [naltrexone + mefene(probably shortening and alteration of methylene).] * * * …   Universalium

  • nalmefene hydrochloride — nal·me·fene hy·dro·chlo·ride (nalґmə fēn″) a derivative of naltrexone that acts as an opioid antagonist, used in the treatment of opioid toxicity and overdose and of postoperative opioid depression; administered parenterally …   Medical dictionary

  • Opioid — Endogenous opioid peptides Skeletal molecular images Adrenorphin Amidorphin Casomorphin …   Wikipedia

  • Drug addiction — is widely considered a pathological state. The disorder of addiction involves the progression of acute drug use to the development of drug seeking behavior, the vulnerability to relapse, and the decreased, slowed ability to respond to naturally… …   Wikipedia

  • Substance dependence — Substance dependency Classification and external resources ICD 10 F10.2 F19.2 ICD 9 …   Wikipedia

  • Sinclair Method — The Sinclair Method is a treatment for alcoholism that involves the use of opiate antagonists such as naltrexone or nalmefene in order to decrease the craving for alcohol over time, while the person continues to consume alcohol. It relies upon a… …   Wikipedia

  • Proglumide — Drugbox IUPAC name = 4 (benzoylamino) 5 (dipropylamino) 5 oxopentanoic acid CAS number = 6620 60 6 ATC prefix = ATC suffix = PubChem = 4922 DrugBank = C=18|H=26|N=2|O=4 molecular weight = 334.41 g/mol bioavailability = protein bound = metabolism …   Wikipedia

  • Amyl nitrite — Not to be confused with amyl nitrate. Amyl nitrite …   Wikipedia

  • Ethanol — For other uses, see Ethanol (disambiguation). Grain alcohol redirects here. It is not to be confused with Neutral grain spirit. Ethanol …   Wikipedia

  • Morphine — This article is about the drug. For other meanings, see Morphine (disambiguation). Morphia redirects here. For other uses, see Morphia (disambiguation). Not to be confused with Morphinae, Morphea, or Morpholine. Morphine …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”