Effects of antihypertensive clonidine congeners on alpha-adrenergic receptors.
Evidence in the literature suggests that the antihypertensive effects of clonidine stem from its action on alpha-2 adrenergic receptors. In order to examine this possibility we tested the effects of 13 congeners of clonidine on the binding of [3H]WB-4101 and [3H]clonidine to calf frontal cortex homogenates; [3H]WB-4101 served as a label for alpha-1 receptors while [3H]clonidine served to label alpha-2 adrenergic receptors. All the substituted imidazolines were two to three orders more potent in inhibiting the binding of [3H]clonidine than they were against [3H]WB-4101. There was a strong correlation between the antihypertensive doses of these congeners and their concentrations required to inhibit the binding of [3H]clonidine. The results are compatible with the concept that the antihypertensive action of clonidine is more likely due to interactions with alpha-2 adrenergic receptors than with alpha-1 receptors.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000959:Antihypertensive Agents; D004146:Dioxanes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine