Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha 2/alpha 1-selectivity of test compounds: (1). Alpha-adrenoceptor antagonists.
Twenty one chemically dissimilar alpha-adrenoceptor antagonists were assessed in 7 different tests. The potencies of the compounds to protect rats from norepinephrine lethality were closely correlated with their potencies for inhibition of [3H]WB4101, but not of [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding to rat brain homogenates. The reverse was found for the potencies of the compounds to prevent the antidiarrheal effect of clonidine. The in vivo anti-norepinephrine/anti-clonidine potency ratios were highly correlated with the ratios between the in vitro potency to inhibit [3H]WB4101 binding on one hand and [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding on the other. The reliability of the above models for measuring alpha 1- and alpha 2-adrenoceptor antagonistic activity and selectivity is discussed.
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000037:antagonists & inhibitors; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D009638:Norepinephrine