Influence of structural changes in the imidazolidine ring of clonidine on hypotensive activity.
2-(2,6-Dichlorophenylimino)piperimidine with HNO3 (St-404), 2-(2,6-dichlorophenyl)-5,6-dihydroimidazo[2,1-b]thiazole fumarate (compound 44-549) and 1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline with HCl (TIQ) were studied with respect to their effects on blood pressure and heart rate in the anaesthetized, normotensive rat following intravenous administration and in the chloralose-anaesthetized cat by means of infusions via the left vertebral artery. St-404 and compound 44-549 possess central hypotensive and bradycardic activities and display modes of action similar to that of clonidine. Central alpha-adrenergic receptors are presumably involved. In the anaesthetized, normotensive rat St-404 is about 3,400 times less active than clonidine, whereas compound 44-549 is 5 times more effective in lowering arterial pressure. The hypotensive effect of TIQ is brought about by a mechanism of action which is different from that of clonidine. The alpha-sympatholytic properties of TIQ suggested previously by others are not confirmed by the experiments presented in this paper.
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*
D000959:Antihypertensive Agents; D007093:Imidazoles; D011799:Quinazolines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013844:Thiazoles; C011147:compound 44-549; C015597:2-(2,6-dichlorophenylimino)piperimidine.HNO3; D003000:Clonidine