Is schedule IV suvorexant an appropriate reference drug of abuse to use in preclinical abuse liability testing in the rat?
| Autor: | Teuns GBA; Global Toxicology and Safety Pharmacology, Janssen Pharmaceutica NV, R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. Electronic address: gteuns@its.jnj.com., Tessari M; Aptuit (Verona) Srl, an Evotec Company, Verona, Italy. |
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| Jazyk: | angličtina |
| Zdroj: | Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2024 Mar; Vol. 148, pp. 105570. Date of Electronic Publication: 2024 Jan 27. |
| DOI: | 10.1016/j.yrtph.2024.105570 |
| Abstrakt: | The abuse potential of novel CNS-active drug candidates with low specificity for known receptors involved in abuse might be complex to test preclinically relative to an appropriate reference drug of abuse. Suvorexant, a Schedule IV dual orexin receptor antagonist was investigated for its potential use as a reference drug in Drug Discrimination Learning (DDL) studies. Firstly, toxicokinetic properties of suvorexant were determined in male and female rats after single oral doses of 160 and 325 mg/kg in MC and PEG400. Thereafter the subjective effects of suvorexant at 325 mg/kg versus vehicle were evaluated in a DDL paradigm and plasma exposures were measured. Mean maximum plasma exposures in male rats after a single dose of 325 mg/kg suvorexant were 2.5- (MC) to 10.5-fold (PEG400) the human exposure at supratherapeutic doses of 40 mg q.d. (C Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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