Trade names Selincro MedlinePlus a605043 ATC code N07BB05 (WHO) | AHFS/Drugs.com Monograph Routes of
administration Oral, Intravenous | |
 | ||
Legal status UK: POM (Prescription only) | ||
Nalmefene (trade name Selincro), originally known as nalmetrene, is an opioid antagonist developed in the early 1970s, used primarily in the management of alcohol dependence. It has also been investigated for the treatment of other addictions such as pathological gambling.
Contents
- Opioid overdose
- Alcohol dependence
- Research
- Side effects
- Pharmacodynamics
- Pharmacokinetics
- Properties
- United States
- Europe
- References
Nalmefene is an opiate derivative similar in both structure and activity to the opioid 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.
Opioid overdose
Intravenous doses of nalmefene have been shown effective at counteracting the respiratory depression produced by opiate overdose, although this is not the usual application for this drug as naloxone is less expensive.
Doses greater than 1.5 mg do not appear to give any greater benefit in this application. The half-life of nalmefene is longer than that of naloxone, which might make it useful for treating overdose involving longer acting opioids such as methadone, in that it would require less frequent dosing and hence reduce the likelihood of renarcotization as the antagonist wears off.
Alcohol dependence
The usefulness of nalmefene is unclear for alcoholism. Nalmefene, in combination with psychosocial management, may decrease the amount of alcohol drank in people who are alcohol dependent. The medication can also be taken "as needed", when a person feels the urge to consume alcohol.
Research
There is a case report of nalmefene being effective as an "as-needed" long-term therapy for cravings in a female patient with cocaine addiction. Nalmefene may possess unique potential in the application of cocaine addiction relative to other opioid antagonists such as naltrexone due to its activity as a partial agonist of the κ-opioid receptor.
Side effects
The most common side effects (seen in more than 1 patient in 10) were nausea (feeling sick), dizziness, insomnia (difficulty sleeping), and headache. The majority or these reactions were mild or moderate and of short duration.
Pharmacodynamics
Nalmefene acts as a silent antagonist of the μ-opioid receptor (MOR) (Ki = 0.24 nM) and as a weak partial agonist (Ki = 0.083 nM; Emax = 20–30%) of the κ-opioid receptor (KOR), with similar affinity for these two receptors but a several-fold preference for the KOR. 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. Side effects typical of KOR activation such as hallucinations and dissociation have also been observed with nalmefene in human studies. It is thought that the KOR activation of nalmefene might produce dysphoria and anxiety. 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 shows agonistic activity.
Nalmefene is structurally related to naltrexone and differs from it by substitution of the ketone group at the 6-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.
Pharmacokinetics
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.
Properties
United States
In the US, immediate-release injectable nalmefene was approved in 1995 as an antidote for opioid overdose. It was sold under the trade name Revex. The product was discontinued by its manufacturer around 2008. Perhaps, due to its price, it never sold well. (See § Opioid overdose, above.}}
Nalmefene in pill form, which is used to treat alcohol dependence and other addictive behaviors, has never been sold in the United States.
Europe
Lundbeck has licensed nalmefene from Biotie Therapies and performed clinical trials with nalmefene for treatment of alcohol dependence. In 2011 they submitted an application for their drug termed Selincro to the European Medicines Agency. The drug was approved for use in the EU in March 2013. and in October 2013 Scotland became the first country in the EU to prescribe the drug for alcohol dependence. England followed Scotland by offering the substance as a treatment for problem drinking in October 2014. In November 2014 nalmefene was appraised and approved as a treatment supplied by Britain's National Health Service (NHS) for reducing alcohol consumption in people with alcohol dependence. Formal guidance on its use was issued by the National Institute for Health and Care Excellence (NICE).