Abstract
The distribution of 14C-timiperone, a butyrophenone antipsychotic, was studied in rat and monkey by means of autoradiography. Tissue levels of radioactivity in the rat at 2h after a single oral administration of 0.5mg of the drug per kg were high in the order of the gastrointestinal contents, liver, urinary bladder, salivary gland, thyroid, pituitary, adrenal, harderian gland, kidney, lung, heart, testis, skeletal muscle and brain. In the rat brain, higher concentrations of radioactivity were detected in the striatum, nucleus accumbens and frontal cortex in which cerebral dopamine receptors were localized, as compared with other brain regions. The tissue levels of radioactivity persisted up to 10h after dosing. Repeated oral administration did not affect the distribution pattern of radioactivity. In the monkey which received a single oral dose of 1mg per kg, tissue levels of radioactivity at 2h after the administration were high in the order of the gastrointestinal contents, gall-bladder, liver, kidney, thyroid, pituitary, salivary gland, lung, heart, eye, blood, bone marrow, skeletal muscle and brain. In the monkey brain, radioactivity was localized in the brain regions including the caudate nucleus, putamen and cortex. The monkey uveal tract had a similar concentration of radioactivity to the blood. Thus, it was confirmed that 14C-timiperone could be transferred to the cerebral dopaminergic systems associated closely with the exhibition of antipsychotic activity of major tranquilizer.
