Psychomotor stimulant effects of the stereoisomers of chlorpheniramine

Abstract

The behavioral effects of the histamine H₁ antagonistsd- andl-chlorpheniramine and of the H₂ antagonist zolantidine were determined in squirrel monkeys responding under a fixed-interval (FI) 3-min schedule of stimulus-shock termination. Althoughd-chlorpheniramine is known to be much more potent thanl-chlorpheniramine for antagonizing H₁ receptor-mediated effects of histamine or displacing [³H]-mepyramine from histamine H₁ receptors, similar doses of racemic chlorpheniramine and thed- andl-isomers (3.0–10.0 mg/kg) produced comparable increases in rates of responding. Zolantidine (1.0–17.0 mg/kg) did not alter or, at the highest dose, markedly decreased responding. These findings suggest that the psychomotor stimulant effects of chlorpheniramine involve actions other than the blockade of histamine H₁ or H₂ receptors. Selected H₁ antagonists and cocaine are known to have comparable rateincreasing, reinforcing, and discriminative stimulus effects and, recently, the enantiomers of chlorpheniramine have been shown to displace [³H]-cocaine from binding sites in CNS with approximately equal potency. Possibly, such actions mediate behavioral effects common to H₁ antagonists and cocaine.