The acute effect of timiperone on the alpha-MT-induced dopamine fluorescence in rat brain.

It has been reported that timiperone, a new butyrophenone, 4'-fluoro-4-[4-(2thioxo -1-benzimidazolynyl) piperidino] butyrophenone, possesses potent antipsychotic activity (Yamasaki et al. 1977; Sato et al. 1978). Tachizawa and co-workers (1979), using a 3 H -spiroperidol binding assay, showed that timiperone inhibited specific 3 H spiroperidol binding in vitro at low concentrations similarly to spiroperidol and was 5 times as potent as haloperidol. In the present fluorescent histochemical in vestigation, we studied on the effect of timiperone on rat central dopaminergic systems in comparison with that of halo peridol by means of formaldehyde-induced fluorescence microscopy (Falck et al. 1962) and quantitative microf luorimetry (Jonsson, 1971). The Wistar strain male rats (200-300 g) were used. Timiperone (0. 1 mg/kg -0. 4 mg/kg) and haloperidol (0.5 mg/kg -2.0 mg/kg) were orally given to rats 5 h. be fore decapitation and DL-alpha-methylparatyrosine (alpha-MT, 250 mg/kg) was injected i. p. 1 h. after the drug administration. Control rats were treated with 0.3 % C. M. C (1 ml/kg) and alpha-MT in the same way as the neuroleptics treated rats. The brains were immediately frozen in isopentane cooled with liquid nitrogen, freeze -dried and treated with formaldehyde gas in accordance with the specific me thod for cellular demonstration of biogenic monoamines described by Falck and Hillarp