Monoaminergic involvement in the pharmacological actions of buspirone

Abstract

1 Buspirone, MJ-13805 and MJ-13653 did not produce a ‘5-hydroxytryptamine (5-HT) syndrome’ in rats at doses up to 20 mg kg⁻¹. 2 These drugs were very weak 5-HT uptake blockers (IC₅₀ ≫ 10 μM) compared to drugs such as chlorimipramine. 3 These drugs did not inhibit either monoamine oxidase (MAO)-A or MAO-B. 4 The K_i values for these agents as inhibitors of [³H]-5-HT and [³H]-ketanserin binding to rat frontal cortex or hippocampal membranes were in the μM range, well above the brain concentrations achieved after an oral dose of 25 mg kg⁻¹. 5 Parenterally administered buspirone blocked apomorphine-induced sterotypy, inhibited the 5-HT syndrome elicited by 5-methoxy-N,N-dimethyltryptamine, and delayed the onset of p-chloroamphetamine induced behaviours.