Motor and cardiovascular effects of selective alpha 2-adrenoceptor antagonists in the decerebrated rabbit

In the decerebrated rabbit, intrathecal administration of the alpha 2-adrenoceptor antagonists idazoxan and yohimbine increases reflex responses of gastrocnemius motoneurones to electrical stimulation of the sural nerve. The maximum effect of idazoxan is about twice that of yohimbine, suggesting that part of the effect of idazoxan may be due to an action at non-adrenergic idazoxan or imidazoline binding sites. RX811059 and RX821002 are selective alpha 2-adrenoceptor antagonists with minimal affinity for imidazoline binding sites. In the present study it was found that intrathecal administration of these compounds in doses of 5-200 micrograms increased the sural-gastrocnemius reflex to the same level as idazoxan, confirming that this reflex is subject to powerful adrenergic inhibition mediated through spinal alpha 2-adrenoceptors. RX811059 and RX821002 also increased arterial blood pressure and heart rate. A retrospective analysis of data from earlier studies showed that whereas intrathecal yohimbine had increased blood pressure, idazoxan had not. It is possible that idazoxan acts at non-adrenergic idazoxan binding sites to cancel out the hypertensive effects which are associated with alpha 2-adrenoceptor blockade.