RT Journal Article
SR Electronic
T1 Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 143
OP 150
DO 10.1124/jpet.102.046318
VO 305
IS 1
A1 Alan P. Kozikowski
A1 Kenneth M. Johnson
A1 Olivier Deschaux
A1 Bidhan C. Bandyopadhyay
A1 Gian Luca Araldi
A1 Gilberto Carmona
A1 Patrik Munzar
A1 Miles P. Smith
A1 Robert L. Balster
A1 Patrick M. Beardsley
A1 Srihari R. Tella
YR 2003
UL http://jpet.aspetjournals.org/content/305/1/143.abstract
AB The present study investigated the pharmacological properties of a piperidine-based novel cocaine analog, namely, (+)-methyl 4β-(4-chlorophenyl)-1-methylpiperidine-3α-carboxylic acid [(+)-CPCA]. Like cocaine, (+)-CPCA inhibited rat synaptosomal dopamine and norepinephrine uptake with high affinity, but was 33-fold less potent than cocaine in inhibiting serotonin uptake. Like cocaine, (+)-CPCA is a locomotor stimulant, although it was less potent and efficacious than cocaine. Importantly, pretreatment with (+)-CPCA dose dependently blocked the locomotor stimulant effects of cocaine in rats. (+)-CPCA completely substituted for cocaine in drug discrimination tests, although it was about 3 times less potent than cocaine. It was also self-administered by rats. Unexpectedly, (+)-CPCA did not enhance cocaine-induced convulsions in mice. As expected from rodent studies, rhesus monkeys readily self-administered (+)-CPCA. However, compared with cocaine, (+)-CPCA showed limited reinforcing properties in rats as assessed by both fixed and progressive ratio intravenous drug self-administration tests. These results collectively suggest that (+)-CPCA has an atypical pharmacological profile having both cocaine-like “agonist” and some cocaine “antagonist” properties. These properties of (+)-CPCA suggest that it may have utility in the treatment of cocaine craving and dependence. U.S. Government