COMPARISON OF THE EFFECTS OF SPEGATRINE AND DISPEGATRINE ON α-ADRENOCEPTORS

Spegatrine (SP), a quaternary alkaloid, was isolated from the water soluble fraction of the roots of Rauvolfia verticillata (Lour.) Bail Var. hainanensis Tsiang. Dispegatrine (DISP), the dimer of SP, is a new principle linked with a covalent bond between the 9′ carbon of both SPs.The affinities and activities of SP and DISP on α-adrenoceptor were studied using radioligand binding experiment and bioassay methods. Presynaptic α₂-antagonist potency was assessed by determining pA₂ values against the inhibitory effect of clonidine on rat vas deferens twitch induced by field stimulation. The pA₂ value for the potency of both compounds on postsynaptic α-1-adrenoceptor was determined by NE on the anococcygeus muscle.The data from the competitive curves showed that the. apparent dissociation constant (K_i) of DISP and SP for al-adrenoceptor was 0.11 _μM and 2.7 _μM; K_i of DISP and SP for α₂-adrenoceptor was 0.047 _μM and 0.65 _μM utilizing ³H WB 4101 or ³H clonidine binding to rat cerebral cortex membrane. The affinity of DISP on α₁ and α₂-adrenoceptor was about an order of magnitude larger than that of SP.In addition, DISP antagonized the inhibitory effects of clonidine on field stimulation twitc hof rat vas deferens(presynaptic α₂-adrenoceptor) and NE-induced contraction of the rat anococcygeus (postsynaptic α₁-adrenoceptor). The pA₂ value of DISP and SP was 5.80 and 5.27 for presynaptic α₂-adrenoceptor in rat vas deferens. The pA₂ value of DISP was 5.8 for postsynaptic α₁-adrenoceptor in rat anococcygeus muscle.The results indicate that the antagonistic effect of DISP on clonidine was 3～4 times as potent as that of SP. DISP produced competitive antagonism of NE-induced contraction of the rat anoccoccygeus muscle. SP inhibited the NE-induced contraction at low concentration of NE, but the contraction can be potentiated by SP at higher concentration of NE. From these results, it appears that the effect of the dimer (EISP) on a-adrenoceptor was more potent than that of monomer (SP).