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behavior of rats and mice administered active metabolites of fluphenazine, 7-hydroxy-fluphenazine and fluphenazine-sulfoxide.

We investigated the effects of 7-hydroxy-fluphenazine and fluphenazine-sulfoxide, main metabolites of fluphenazine (FZ), on behavior of mice and rats. These metabolites inhibited open-field behavior and methamphetamine-induced hyperactivity, lowered body temperature, and elicited catalepsy in mice, as did FZ-2HCl, FZ-enanthate and FZ-decanoate. After intramuscular administration, the onset of action of FZ-enanthae, FZ-decanoate and their metabolites was somewhat delayed compared to findings with FZ-2HCl, and the duration of FZ-enanthate and FZ-decanoate lasted longer than that of FZ-2HCl and metabolites. FZ-metabolites decreased stereotypy induced by a high dose (4 mg/kg, i.p.) of apomorphine and yawning elicitedby a low dose (0.25 mg/kg i.p.) of apomorphine in rats. The results suggest that 7-hydroxy-FZ and FZ-sulfoxide exert their psychotropic actions by blocking pre- and postsynaptic dopamine receptors and that formation of active metabolite may affect theprolonged therapeutic action of depot-type preparations of FZ.