title: Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery.
abstract: The antagonistic effects of MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine at rat thoracic aorta and rabbit iliac artery alpha1-adrenoceptors were investigated in this study. Selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin dose-dependently shifted the concentration-response curves for noradrenaline to the right. Schild plots of the results obtained from the inhibition by MDL73005EF (pA2 8.30 +/- 0.04) and tamsulosin (pA2 10.51 +/- 0.06) of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta. The slopes of Schild plots obtained from the inhibition by MDL73005EF and tamsulosin of noradrenaline were significantly different from unity in rabbit iliac artery. Schild plots of the results obtained from the inhibition by clonidine and tizanidine of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta (pA2 7.08 +/- 0.04 and 7.32 +/- 0.04, respectively). These results suggest that alpha1D-adrenoceptors play a significant role in the alpha1-adrenoceptor-agonist-induced contraction of rat thoracic aorta and rabbit iliac artery, and that clonidine and tizanidine interact with the alpha1D-adrenoceptor subtype as competitive antagonists in rat thoracic aorta.
authors.affiliation: Department of Chemical Pharmacology, Toho University, School of Pharmaceutical Sciences, Funabashi,Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Enomoto
authors.forename: K
authors.initials: K
authors.lastname: Koike
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D007083:Iliac Artery / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000077409:Tamsulosin
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004147:Dioxins; D018340:Receptors, Adrenergic, alpha-1; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; C063249:binospirone mesylate; C023754:tizanidine; D000077409:Tamsulosin; D003000:Clonidine