The influence of zimelidine and clomipramine on two p-chloroamphetamine (PCA)- or fenfluramine-induced pharmacological effects, regarded as resulting from the serotoninergic stimulation, was studied. In the flexor reflex test in the spinal rat zimelidine prevented potentiation induced by PCA but not that induced by fenfluramine. Clomipramine antagonized both the PCA- and fenfluramine-induced effects. Zimelidine counteracted also the hyperthermia in rats induced by PCA at a high ambient temperature but not that induced by fenfluramine. These findings seem to indicate that: (1) zimelidine and clomipramine differ in their mechanism of presynaptic action on serotonin neurons; (2) fenfluramine and PCA are taken up to serotonin neurons via different mechanisms.

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