Selectivity of raubasine stereoisomers for alpha 1- and alpha 2-adrenoceptors in the rat.

The selectivity of raubasine and its two isomers tetrahydroalstonine (THA) and akuammigine (AKU) for alpha 1- and alpha 2-adrenoceptors has been investigated in pithed normotensive rats. alpha 1-Adrenoceptor blockade was measured by inhibition of the pressor response to (-)-phenylephrine. alpha 2-Adrenoceptor blockade was measured by antagonism of the inhibitory effect of clonidine both on the tachycardia produced by electrical stimulation of the cardiac accelerator nerves and on the pressor response to B-HT 933. Pressor responses to (-)-phenylephrine were reduced in a dose-dependent manner by raubasine but not by THA and AKU. The inhibitory effect of clonidine and the pressor response to B-HT 933 were antagonized in a dose-dependent manner by THA but not by raubasine and AKU. These results indicate that, in pithed rats, AKU is a very weak antagonist at alpha 1- and alpha 2-adrenoceptors, raubasine is a preferential alpha 1-adrenoceptor antagonist, and THA is a selective alpha 2-adrenoceptor antagonist.