Alpha 2-adrenoceptor-blocking properties of midaglizole (DG-5128) in rats.

The alpha 2-adrenoceptor antagonistic potency of midaglizole was evaluated and compared with that of the selective alpha 2-adrenoceptor antagonists yohimbine and idazoxan. Intravenously administered midaglizole, like yohimbine and idazoxan, reversed the clonidine-induced inhibition of the tachycardic response to cardiac nerve stimulation in pithed rats. Midaglizole, yohimbine and idazoxan inhibited the pressor responses to B-HT 920 (alpha 2-adrenoceptor agonist), in a dose-related manner, to a greater extent than the response to methoxamine (alpha 1-adrenoceptor agonist). Conversely, prazosin produced a highly selective antagonism of the methoxamine-evoked response in this preparation. Midaglizole failed to antagonize centrally mediated hypotension and bradycardia induced by intravenous clonidine, whereas the other alpha 2-antagonists attenuated the clonidine-induced cardiovascular responses in intact rats. These results suggest that midaglizole is a selective alpha 2-adrenoceptor antagonist and, unlike yohimbine and idazoxan, is characterized by its ability to block peripheral but not central alpha 2-adrenoreceptors when administered systemically.