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

Eur J Pharmacol. 2000 Aug 4;401(2):197-204. doi: 10.1016/s0014-2999(00)00441-6.

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; CCK(1) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Analgesics / pharmacology*
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Discrimination Learning / drug effects
  • Discrimination, Psychological / drug effects*
  • Disulfides / pharmacology*
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology
  • Male
  • Meglumine / analogs & derivatives
  • Meglumine / pharmacology
  • Morphine / pharmacology
  • Protease Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Analgesics
  • Anti-Anxiety Agents
  • Disulfides
  • Indoles
  • Protease Inhibitors
  • RB 120
  • PD 134308
  • Meglumine
  • Morphine
  • Alanine