Time-related changes in serum perphenazine, striatal 3H-spiperone binding and regional brain acid metabolites of dopamine and 5-hydroxy-tryptamine after a single dose of perphenazine.

A single dose of perphenazine (5.0 mg/kg) was administered intraperitoneally to male Wistar rats. The time-related alterations in serum levels of perphenazine, striatal 3H-spiperone binding ex vivo and the regional brain metabolism of dopamine and 5-hydroxy-tryptamine were studied. Low serum levels of perphenazine were observed together with increased Kd of 3H-spiperone. No significant changes in Bmax were observed. Since Kd of 3H-spiperone binding peaked several hours after the maximal serum levels of perphenazine, perphenazine in serum appeared not to directly reflect the events at the receptor level. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy, 4-hydroxyphenylacetic acid (HVA) in the striatum were increased after perphenazine. They were maximal 1-3 h after the drug administration and showed positive correlations (correlation coefficient 0.93 and 0.80, respectively) with the serum levels of perphenazine. Increased levels of HVA were also observed both in the olfactory tubercle and in the frontal cortex. However, in the olfactory tubercle, administration of perphenazine did not significantly increase the DOPAC concentrations. In the olfactory tubercle 5-hydroxyindoleacetic acid (5-HIAA) was decreased 1-24 h after administration of perphenazine. In the striatum and in the frontal cortex only slight changes in 5-HIAA were seen. Thus, in the olfactory tubercle 5-hydroxytryptaminergic mechanisms could modulate the dopaminergic neurotransmission.