Dopamine receptor stimulating effects of chanoclavine analogues, tricyclic ergot alkaloids, in the brain.

The abilities of tricyclic ergot alkaloids, chanoclavine-I and its analogues, and bromocriptine to stimulate dopamine receptors in the brain were investigated. Receptor binding of 3H-spiperone has shown that bromocriptine exhibits clear affinity for this compound. The order of displacement potencies was bromocriptine much greater than ergometrine, KSU-1415 greater than chanoclavine-I, KSU-1118, KSU-1791. In the striatum of mice treated with an amino acid decarboxylase inhibitor, gamma-butyrolactone-induced DOPA accumulation was markedly inhibited by bromocriptine and KSU-1415, but not inhibited by chanoclavine-I. In mice with unilateral striatal 6-hydroxydopamine lesions, bromocriptine and KSU-1415 produced a long-lasting contralateral rotation that was suppressed by prior treatment with (+/-)-sulpiride. These results suggest that a tricyclic ergot alkaloid of the chanoclavine type stimulates D-2 receptors in the brain.