Nalmefene

Structural formula
General
Non-proprietary name	Nalmefene
other names	(5 R , 9 R , 13 S , 14 S ) -17-Cyclopropylmethyl-6-methylene-4,5-epoxymorphinan-3,14-diol ( IUPAC )
Molecular formula	C 21 H 25 NO 3
Brief description	white solid (hydrochloride dihydrate)
External identifiers / databases
EC number	637-223-3
ECHA InfoCard	100.164.948
PubChem	5284594
ChemSpider	4447642
DrugBank	DB06230
Wikidata	Q4353252
Drug information
ATC code	N07 BB05
Drug class	Opioid antagonist
properties
Molar mass	339.43 g · mol -1
Physical state	firmly
Melting point	188-190 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-319-335
	P: 261-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Nalmefene is an opioid antagonist that was developed in the 1970s. Previously used as an antidote to treat opiate poisoning, it has been used in the treatment of alcoholism since September 1, 2014 .

Pharmacological properties

Mechanism of action

Nalmefene selectively binds to the opioid receptors . It has an antagonistic activity on the μ- and δ-receptors and a partial agonistic activity on the κ-receptors.

Acute alcohol consumption leads to a release of dopamine in the mesolimbic system , which functions as a “positive reward system” and plays a role in the development of addiction. It is believed that nalmefene modulates cortico-mesolimbic functions, suppresses positive reinforcement, and thus can reduce alcohol consumption.

Pharmacokinetics

After oral administration, the maximum plasma concentration is reached after 1 - 1.5 hours; the half-life is 13 hours. At the site of action, the brain, up to 100% of the µ-opioid receptors are occupied within three hours. The occupancy only subsides slowly - 50 hours after ingestion, more than half of the receptors are still blocked. After absorption, nalmefene is rapidly and extensively metabolized and excreted primarily through the kidneys. The main metabolite is nalmefene-3- O- glucoronide.

Use to treat alcoholic disease

Nalmefene was approved in the EU in March 2013 and has also been approved in Germany under the trade name Selincro since September 1, 2014 for the reduction of alcohol consumption in adult patients with alcohol dependence, whose alcohol consumption is at a high risk level and who have no physical withdrawal symptoms. Studies have shown that it is suitable for patients who drink in a higher risk range (men more than 60 grams of pure alcohol per day, women more than 40 grams of pure alcohol per day, according to WHO drinking risk levels , DRLs), who drink not without their drinking amount Can reduce drug support and are not so seriously ill that withdrawal has to be carried out in an inpatient setting due to withdrawal symptoms. Selincro is taken as needed; In other words , if the patient assumes that they are in a situation associated with alcohol consumption, or if they feel another risk of drinking alcohol, Selincro should be taken one to two hours before the expected alcohol consumption.

effectiveness

The number of heavy drinking days (more than 60 grams (men) or 40 grams (women) of pure alcohol per day) among the patients who drank at a high risk level at the beginning and could not reduce the amount they drank without drug therapy fell in both of them Approval studies within 24 weeks of an average of 23 to 10 or 9 days per month. The reduction in the amount of alcohol consumed corresponded to just under a bottle of wine over the same period. Patients who received placebo in the studies were also able to reduce the amount they drank to a relevant extent, but not as much as the patients who received nalmefene. At the same time, the improvement in general clinical condition and liver function tests was greater in patients with nalmefene than in patients with placebo. Both groups of patients (both the nalmefene group and the placebo group) received the same psychosocial support.

Side effects and interactions

Side effects reported by more than 10% of patients in the pivotal studies included dizziness, nausea, difficulty sleeping, fatigue, headache, and nasopharynx inflammation. These side effects partially led to the discontinuation of the medication. However, there was no evidence of changes in laboratory parameters, cardiovascular functions, weight or mood that were relevant to treatment. Simultaneous use of Selincro and medicines containing opioids (e.g. certain cough and cold medicines, certain medicines for the treatment of diarrhea and certain painkillers, including substitution medicines in the treatment of opiate addiction) can weaken or cancel the effect of the aforementioned medicines. Relevant interactions between alcohol and nalmefene are not described.

Pharmaceutical information

Nalmefene requires a prescription . In Selincro , the active ingredient is used in the form of nalmefene hydrochloride dihydrate (contains 18.06 mg nalmefene per tablet).

Web links

Entry on nalmefene in Pharmawiki
NALMEFEN (SELINCRO) FOR ALCOHOL DEPENDENCE. In: arznei-telegramm.de. September 1, 2014, accessed January 29, 2017 .

Individual evidence

↑ European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP): Assessment report - Selincro (EMA / 78844/2013, 13 December 2012) .

↑ Entry on Nalmefene in the ChemIDplus database of the United States National Library of Medicine (NLM)

↑ ^a ^b Data sheet Nalmefene from Sigma-Aldrich , accessed on May 25, 2017 ( PDF ).

↑ US patent 3814768 , Jack Fishman et al .: 6-METHYLENE-6-DESOXY DIHYDRO MORPHINE AND CODEINE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS , published November 26, 1971, issued June 4, 1974.

^ DS Wang, G. Sternbach, J. Varon: Nalmefene: a long-acting opioid antagonist. Clinical applications in emergency medicine. In: J Emerg Med. 16, 1998, pp. 471-475.

↑ Information on Selincro on the EMA website

↑ ^a ^b K. Mann, A. Bladström, L. Torup, A. Gual, W. van den Brink: Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. In: Biol Psychiatry. 73, 2013, pp. 706-713.

↑ ^a ^b A. Gual, Y. He, L. Torup, W. van den Brink, K. Mann, for the Esense 2 Study Group: A randomized, double-blind, placebo-controlled, efficacy study of nalmefene, as- needed use, in patients with alcohol dependence. In: Eur Neuropsychopharmacol. 23, 2013, pp. 1432-1442.

^ W. Van den Brink, HJ Aubin, A. Bladström, L. Torup, A. Gual, K. Mann: Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies. In: Alcohol Alcoholism. 48, 2013, pp. 570-578.

[ema-1] European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP): Assessment report - Selincro (EMA / 78844/2013, 13 December 2012) .

[2] Entry on Nalmefene in the ChemIDplus database of the United States National Library of Medicine (NLM)

[Sigma-3] Data sheet Nalmefene from Sigma-Aldrich , accessed on May 25, 2017 ( PDF ).

[4] US patent 3814768 , Jack Fishman et al .: 6-METHYLENE-6-DESOXY DIHYDRO MORPHINE AND CODEINE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS , published November 26, 1971, issued June 4, 1974.

[5] DS Wang, G. Sternbach, J. Varon: Nalmefene: a long-acting opioid antagonist. Clinical applications in emergency medicine. In: J Emerg Med. 16, 1998, pp. 471-475.