title: Quantitative structure-activity relationships in centrally acting imidazolidines structurally related to clonidine.
abstract: The central hypotensive action of clonidine and 26 structurally related derivatives was quantified by means of an ED30 obtained from dose-response curves following intravenous administration to anesthetized, normotensive rats. Multiple regression analyses of the biological data yielded correlation equations comprising a relationship between hypotensive activity and molecular structure. In the equations the pharmacokinetics together with the actual engagement of the central alpha-adrenoceptor are accounted for. More detailed characteristics of this central alpha-adrenoceptor emerged from correlation studies in which new ED30 values, associated with brain concentrations, were employed. The use of this biological parameter at the alpha-adrenoceptor level allowed the presentation of a hypothetical working model for the mechanism of interaction between this receptive site and clonidine-like imidazolidines.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003864:Depression, Chemical; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D011942:Receptors, Adrenergic, alpha; D003000:Clonidine