title: Placebo- and amitriptyline-controlled evaluation of central nervous system effects of the NK1 receptor antagonist aprepitant and intravenous alcohol infusion at pseudo-steady state.
abstract: Recent interest in NK1 receptor antagonists has focused on a potential role in the treatment of drug addiction and substance abuse. In the present study, the potential for interactions between the NK1 receptor antagonist aprepitant and alcohol, given as an infusion at a target level of 0.65 g/L, was evaluated. Amitriptyline was included as positive control to provide an impression of the profile of central nervous system (CNS) effects. In a double-blind, randomized, placebo- and amitriptyline-controlled study, the pharmacokinetics and CNS effects of aprepitant and alcohol were investigated in 16 healthy volunteers. Cognitive and psychomotor function tests included the visual verbal learning test (VVLT), Bond and Lader visual analogue scales (VAS), digit symbol substitution test (DSST), visual pattern recognition, binary choice reaction time, critical flicker fusion (CFF), body sway, finger tapping, and adaptive tracking. Alcohol impaired finger tapping and body sway. Amitriptyline impaired DSST performance, VAS alertness, CFF, body sway, finger tapping, and adaptive tracking. No impairments were found after administration of aprepitant. Co-administration of aprepitant with alcohol was generally well tolerated and did not cause significant additive CNS effects, compared with alcohol alone. Therefore, our study found no indications for clinically relevant interactions between aprepitant and alcohol.
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands. etbeek@chdr.nl
authors.forename: Erik T
authors.initials: ET
authors.lastname: te Beek
authors.forename: Daniel
authors.initials: D
authors.lastname: Tatosian
authors.forename: Anup
authors.initials: A
authors.lastname: Majumdar
authors.forename: Diana
authors.initials: D
authors.lastname: Selverian
authors.forename: Erica S
authors.initials: ES
authors.lastname: Klaassen
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Petty
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gargano
authors.forename: Kristien
authors.initials: K
authors.lastname: van Dyck
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McCrea
authors.forename: Gail
authors.initials: G
authors.lastname: Murphy
authors.forename: Joop M A
authors.initials: JM
authors.lastname: van Gerven
mesh_terms: D000293:Adolescent; D000328:Adult; D000639:Amitriptyline; D000077608:Aprepitant; D002490:Central Nervous System / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011597:Psychomotor Performance / Q000187:drug effects; D055815:Young Adult
chemical_list: D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000639:Amitriptyline; D000077608:Aprepitant; D000431:Ethanol
keywords: NK1 receptor; addiction; alcohol; amitriptyline; aprepitant; interaction; pharmacodynamics; pharmacokinetics; substance abuse