Yohimbine diastereoisomers: cardiovascular effects after central and peripheral application in the rat

The cardiovascular effects of four yohimbine diastereoisomers, yohimbine, rauwolscine, corynanthine, and 3-epi-alpha-yohimbine, were compared in urethane-anaesthetized and conscious, normotensive Sprague-Dawley rats. Intravenous cumulative infusions (10--500 microgram) of the drugs to anaesthetized rats decreased blood pressure and blunted the pressor response to intravenous adrenaline injections. Corynanthine was the most potent isomer in this regard, followed by yohimbine, rauwolscine, and 3-epi-alpha-yohimbine. Depressor responses following intravenous bolus doses (40 microgram) showed a similar ranking. Intraventricular injections of yohimbine to anaesthetized rats decreased blood pressure dose-dependently, as did injections of corynanthine and rauwolscine. Responses indicated the ranking to be yohimbine greater or equal to rauwolscine greater than corynanthine for this effect at the 40 microgram dose. Heart rate was also decreased by these isomers, but not in a dose-dependent fashion. In conscious rats, the intraventricular injection of these isomers (20 microgram) increased blood pressure and heart rate. No differences were noted in terms of blood pressure responses; but, in causing tachycardia, the ranking was rauwolscine greater than yohimbine greater than corynanthine. These data suggest that after intraventricular application in anaesthetized rats, the effects of these alpha-adrenoceptor blockers are related to their individual affinity for the alpha 2 adrenoceptor.