• 作者： 曾清俊; 陳紹原; 陶寶綠; 陳基旺; 顏茂雄
• 作者服務機構： 國防醫學院藥理學科及藥學系; 高雄榮民總醫院教學研究部
• 中文摘要： 　　本研究之主要目的在利用活體及離體實驗，探討我們所合成之新的降血壓藥物AT-112降血壓作用及可能之作用機轉。在活體動物實驗中，由中樞或周邊給予AT-112均可在清醒自發性高血壓大白鼠造成降壓之作用。在離體實驗中，我們發現AT-112對胸主動脈之血管擴張作用與血管內皮存在與否有關，同時我們亦發現AT-112為 -adrenergic接受器之競爭性對抗劑，而非serotonin之競爭性抑制劑。Ketanserin及AT-112對phenylephrine之IC50分別為27.8 nM及0.36nM。另外，競爭性結合研究顯示AT-112對　-adrenergic接受器及　-adrenergic接受器之親和力(affinity)分別為2.01±0.09 nM及3.86±0.64 nM。經由以上活體、離體及競爭性結合研究，AT-112是一極強之降血壓藥物，且其降壓作用主要是經由抑制　-adrenergic接受器。
• 英文摘要： The purpose of this study was to investigate the anti-hypertensive effect and possible mechanism ofaction of 2-(4-phenyl-l-piperazinyl)methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one (AT-112), a newlysynthesized ketanserin derivative, on in vivo and in vitro models. In vivo, central and peripheral administra-tion of AT-112 produced a dose-dependent decrease of arterial blood pressure in conscious spontaneouslyhypertensive rats (SHR). In in vitro study, the vasodilating effect of AT-112 on isolated thoracic aortawas endothelium-independent. AT-112 was found to be a potent 1-adrenoceptor blocking agent in therat thoracic aorta as revealed by its competitive antagonism of phenylephrine (pA2 = 9.82 ± 0.19), butwas found to have noncompetitive antagonism to 5-HT. The IC5O of ketanserin and AT-112 to phenyle-phrine were 27.8 nM and 0.36 nM, respectively, and to 5-HT were 5.73 nM and 0.44 M, respectively.Competition binding studies demonstrated that the affinity of AT-112 to -adrenoceptor (Ki = 2.01 ± 0.09nM) was significantly higher than that of -adrenoceptor (Ki = 3.86 ± 0.64 MM). Based on the resultsof these in vivo, in vitro and competition binding studies, AT-112 is a potent antihypertensive agent, andits antihypertensive action is mainly mediated by the blockade of the l-adrenoceptor.
• 中文關鍵字： AT-122; antihypertension; SHR; isolated thoracic aorta; α1-adrenergic receptor; 5-HT.
• 英文關鍵字： --