A new central direct dopaminergic stimulant: 1 (coumaran 5 yl methyl) 4 (2 thiazolyl) piperazine hydrochloride (S 3608)

Article abstract of DOI:10.1007/BF02326795

The central stimulating effect of S 3608 in the rat induced a stereotyped behavioural response, similar to that of apomorphine. The intensity of stimulation was self limited and increasing the dosage of S 3608 above 40 mg/kg did not modify the response. The stereotyped response was only enhanced in higher doses in the case of apomorphine. On the contrary, these changes were not observed with S 3608 indicating the central stimulant effect is different in nature or intensity. S 3608 and Piribedil induced turning in rats, contralateral to a lesion in the substantia nigra. The 2 compounds have a sustained effect, the central dopaminergic stimulant potency being comparable. S 3608 exerted a delay on the onset of morphine catatonia, modifying the ED₅₀ of the analgesic. Ergocornine an CB 154 behaved as powerful antagonists on morphine catatonia, the former compound inducing peripheral neurovegetative signs, but the antagonistic effect of CB 154 was observed without any vegetative signs. Yohimbine modified the morphine rigidity, indicating that a block of the central sympathetic activity may be detected in the morphine model, as well as a strong direct dopaminergic stimulant effect. The data support the hypothesis that S 3608 is a new direct central dopamine stimulant, different from apomorphine, qualitatively and quantitatively. In the rotation model, the potency of stimulation is similar to that of Piribedil. Further experiments are in progress to elucidate the mechanism of action of S 3608 on central dopaminergic and noradrenergic mechanisms.