Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have discriminative stimulus properties.
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.
Hutcheson
D M
DM
Department of Experimental Psychology, University of Cambridge, Downing St., CB2 3EB, Cambridge, UK.
Subhan
F
F
Pache
D M
DM
Maldonado
R
R
Fournié-Zaluski
M
M
Roques
B P
BP
Sewell
R D
RD
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D014151:Anti-Anxiety Agents; D004220:Disulfides; D007211:Indoles; D011480:Protease Inhibitors; C110978:RB 120; C065599:PD 134308; D008536:Meglumine; D009020:Morphine; D000409:Alanine