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Placebo‐ and Amitriptyline‐Controlled Evaluation of Central Nervous System Effects of the NK 1 Receptor Antagonist Aprepitant and Intravenous Alcohol Infusion at Pseudo‐Steady State
Author(s) -
te Beek Erik T.,
Tatosian Daniel,
Majumdar Anup,
Selverian Diana,
Klaassen Erica S.,
Petty Kevin J.,
Gargano Cynthia,
van Dyck Kristien,
McCrea Jacqueline,
Murphy Gail,
van Gerven Joop M.A.
Publication year - 2013
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.120
Subject(s) - aprepitant , placebo , anesthesia , amitriptyline , finger tapping , digit symbol substitution test , psychology , pharmacology , medicine , vomiting , audiology , alternative medicine , pathology , antiemetic
Recent interest in NK 1 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 NK 1 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.