Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have discriminative stimulus properties

Daniel M. Hutcheson, Fazal Subhan, David M. Pache, Rafael Maldonado, Marie Claudé Fournié-Zaluski, Bernard P. Roques, Robert D.E. Sewell*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

The systemically active mixed inhibitor of enkephalin metabolism, N-((S)-2-benzyl-3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benzylester (RB 120), alone or in combination with 4-{[2-[[3-(1H-indol-3-yl))-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1.]dec-2-yloxy) carbonyl]amino}propyl]amino]-1-phenylethyl]amino}-4-oxo-[R-(R*,R*)]-butanoate N-methyl-D-glucamine (CI 988; CCK1 receptor antagonist) was investigated for discriminative and morphine generalisation effects using an operant drug discrimination paradigm in rats. Animals dosed with RB 120 (10 mg/kg) failed to develop a discriminative response. Combined CI 988 (0.3 mg/kg) and RB 120 (10 mg/kg) also failed to elicit a discriminative response. Morphine-trained animals (3.0 mg/kg) did not generalise to RB 120 (10 and 20 mg/kg). Similarly, subsequent retraining of the same animals with 1.5 mg/kg of morphine did not elicit generalisation to RB 120 (10 or 20 mg/kg). Combined RB 120 (10 or 20 mg/kg) and CI 988 (0.3 or 3.0 mg/kg) treatment produced no notable drug lever selection in rats able to discriminate morphine (1.5 mg/kg) from saline. These results suggest that RB 120 may have low abuse potential at analgesic doses. Copyright (C) 2000.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalEuropean Journal of Pharmacology
Volume401
Issue number2
DOIs
Publication statusPublished - 4 Aug 2000
Externally publishedYes

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    Hutcheson, D. M., Subhan, F., Pache, D. M., Maldonado, R., Fournié-Zaluski, M. C., Roques, B. P., & Sewell, R. D. E. (2000). Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have discriminative stimulus properties. European Journal of Pharmacology, 401(2), 197-204. https://doi.org/10.1016/S0014-2999(00)00441-6