P-TYPE CALCIUM CHANNELS ARE BLOCKED BY THE ALKALOID DAURISOLINE

IN looking for a structurally defined non-peptide P-channel blocker we have tested the alkaloid daurisoline which has been isolated from tra ditional Chinese medicinal herb (Menispermum dauricum) used for the tr eatment of epilepsy, hypertension and asthma. We have found that dauri soline is an inhibitor of omega-Aga-IVA sensitive barium currents in c erebellar Purkinje cells and of excitatory postsynaptic potentials evo ked in Purkinje cells by stimulating parallel fibres in acutely prepar ed cerebellar slices. Daurisoline did not significantly affect omega-A ga-IVA-insensitive barium currents recorded from granule cells freshly isolated from rat cerebellum. Daurisoline passes the blood-brain barr ier and will, therefore, facilitate the functional characterization of brain calcium channels as well as the exploration of P-type calcium c hannels as possible drug targets.