Abstract
1. 1. The effect of the diphenylmethyl-piperazine derivative dotarizine on K +-stimulated release of [ 3H]serotonin ([ 3H]5-HT) and [ 3H]acethylcholine ([ 3H]Ach) in rat hippocampal slices was studied. 2. 2. Dotarizine at a concentration of 10 −6 M significantly decreased the basal [ 3H]5-HT release and, at a concentration of 10 −5 M, it significantly decreased the K +-stimulated [ 3H]5-HT release compared to vehicle controls. 3. 3. Dotarizine, at a concentration of 5 × 10 −7 M, significantly increased both basal and K +-stimulated [ 3H]Ach release. At higher concentrations (10 −6 and 2 × 10 −6 M), dotarizine did not change the basal release but significantly increased the K +-stimulated [ 3H]Ach release. The effect of dotarizine on K +-stimulated [ 3H]Ach release decreased with increasing dotarizine concentrations. 4. 4. It is speculated that, in addition to its Ca 2+ antagonistic activity, dotarizine exerts an antagonistic effect on the presynaptic 5-HT autoreceptors, which could account for the facilitation of [ 3H]Ach release.
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