Influence of the new 5-HT-uptake inhibitor paroxetine on hypermotility in rats produced by p-chloroamphetamine (PCA) and 4,?-dimethyl-m-tyramine (H 77/77)

Abstract

Two different forms of hypermotility produced by the amphetamine derivatives PCA and H 77/77, 5 mg/kg of each, was studied in rats treated s.c. with the new 5-HT uptake inhibitor paroxetine. The substance inhibited the effect of PCA but did not influence that of H 77/77. The 5-HT-uptake inhibitors paroxetine, imipramine, and chlorimipramine were also administered p.o. at various times before PCA. The three substances inhibited PCA-induced hypermotility. Paroxetine 0.5-2 mg/kg, was active at intervals of 1-4 h and 4 mg/kg was active at 18-h interval. Imipramine and chlorimipramine 25-30 mg/kg showed PCA inhibition at treatment intervals of 1-2h, but 80-100 mg/kg or more was required to inhibit PCA at intervals of 4 and 18 h. Previous results have shown that PCA-induced hypermotility is antagonized by substances inhibiting 5-HT synthesis and uptake, whereas H 77/77-induced hypermotility is inhibited by substances blocking NA synthesis, uptake, and receptors. The previous and present results indicate that paroxetine is a selective 5-HT-uptake inhibitor. After oral administration paroxetine presumably produces a more potent and long-lasting 5-HT-uptake inhibition than imipramine and chlorimipramine.