The effect of d- and 1-isomers of fenfluramine and norfenfluramine on stereotypy induced by high doses of amphetamine and apomorphine, and hypermotility caused by lower doses of amphetamine was studied in rats. d-Fenfluramine and d-norfenfluramine were more potent than the 1-isomers in reducing all the effects studied. Norfenfluramine was found to be more active than fenfluramine. However, 1-fenfluramine was as potent as the d-isomer and more potent than 1-norfenfluramine in reducing amphetamine stereotypy. Fenfluramine was particularly potent in inhibiting amphetamine stimulation and this effect could not be attributed to a reduction of brain levels of amphetamine caused by fenfluramine pretreatment. While for 1-fenfluramine and 1-norfenfluramine a direct effect on dopaminergic mechanisms cannot be excluded with certainty, it is suggested that d-fenfluramine and d-norfenfluramine effects on drug stimulation are indirectly mediated. A serotonergic component, as for their effect on food intake, is postulated.
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