Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha 2/alpha 1-selectivity of test compounds: (2). Alpha-adrenoceptor agonists.
Eighteen chemically dissimilar alpha-adrenoceptor agonists were assessed in 6 different tests. The antidiarrheal activity of the compounds was highly correlated with the diuretic activity. Both activities were highly correlated with the inhibition of [3H]clonidine or [3H]idazoxan binding; the degree of correlation with inhibition of [3H]WB4101 binding or with antiptotic activity was much less. Antiptotic activity was better correlated, although still poorly, with inhibition of [3H]WB4101 binding than with inhibition of [3H]clonidine or [3H]idazoxan binding. The in vivo antiptotic/diuretic or antiptotic/antidiarrheal potency ratios both reflected the known alpha 2/alpha 1-selectivity of the compounds tested and were significantly correlated with the in vitro potency ratios between inhibition of [3H]WB4101 binding on one hand and of [3H]clonidine or [3H]idazoxan binding on the other. The reliability of the above models for measuring alpha 1- and alpha 2-adrenoceptor agonistic activity and selectivity is discussed.
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000930:Antidiarrheals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004232:Diuretics; D066298:In Vitro Techniques; D011224:Prazosin / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects* / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000930:Antidiarrheals; D004232:Diuretics; D011942:Receptors, Adrenergic, alpha; D011224:Prazosin