Administration of the metabotropic glutamate receptor subtype 5 allosteric modulator GET 73 with alcohol: A translational study in rats and humans. (February 2018)

• Record Type: Journal Article
• Authors: Haass-Koffler, Carolina L; Goodyear, Kimberly; Loche, Antonella; Long, Victoria M; Lobina, Carla; Tran, Harrison H; Cacciaglia, Roberto; Swift, Robert M; Colombo, Giancarlo; Leggio, Lorenzo
• Is Part Of: Journal of psychopharmacology. Volume 32:Number 2(2018)
• Page Start: 163
• Page End: 173
• Publication Date: 2018-02
• Subjects: Rats -- humans -- metabotropic glutamate receptor subtype 5 -- alcohol -- sedation/hypnosis safety -- pharmacokinetics; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881117746904
• Languages: English
• ISSNs: 0269-8811

Abstract

Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative allosteric modulator, may represent a novel pharmacological treatment for alcohol use disorder. Two independent experiments evaluated the effect of acutely administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced hypolocomotion ( n =72) and sedation/hypnosis ( n =36) in rats. In healthy male volunteers ( n =14), an open-label, randomised, crossover study was conducted to compare adverse events and pharmacokinetic parameters, in two experiments in which 300 mg GET 73 was administered, with and without alcohol, once and thrice. In rats, when administered with alcohol-vehicle, 100 mg/kg, but not 30 mg/kg, GET 73 reduced spontaneous locomotor activity. When administered with alcohol, no dose of GET 73 altered either alcohol-induced hypolocomotion or sedation/hypnosis. In humans, both single and thrice 300 mg GET 73 administration were well tolerated, in the presence and absence of alcohol, with no differences in adverse events. There were no significant differences in relative bioavailability between administering 300 mg GET 73 in the presence or absence of alcohol.