Selective interaction of DG-5128 with a low agonist affinity state of alpha-2 adrenoceptor.

Using rat cerebral cortex membranes, the inhibitory effect of DG-5128 against (3H)-clonidine binding was compared between low (alpha 2L) (in the presence of EDTA) and high (alpha 2H) affinity states (in the presence of excess magnesium) of alpha 2-adrenoceptor for agonists. The Ki value (pKi=6.79) of DG-5128 in the alpha 2L state was 6.4 times higher than the value in the alpha 2H state. Thus, DG-5128 produces alpha 2-adrenoceptor antagonism through the selective interaction with an alpha 2L state of the receptor.