Lin Chia Hsien, Lin Mei Shan, Lin Ying Hsiu, Chen I Ming, Lin Pen Rong, Cheng Chen-Yu, Tsai Ming Cheng
Department of Pharmacology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, Taiwan, ROC.
Pharmacology. 2003 Apr;67(4):202-10. doi: 10.1159/000068402.
The pharmacological effects of BDPBI (7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride) were tested on isolated endothelium-containing or denuded aorta of the guinea pig. BDPBI with the formula C(27)H(24)BrCl(2)N(3)O was synthesized starting with 3-isochromanone. In the endothelium-containing preparations of the aortic rings, phenylephrine (PHE; 10 micromol/l) elicited contracture and acetylcholine (ACh; 10 micromol/l) or BDPBI (0.01-10 micromol/l) elicited relaxation effects on the PHE-precontracted preparations. The BDPBI-elicited effect on the PHE-precontracted aortic rings was not altered in the presence of adrenergic blockers (propranolol or yohimbine; 1 micromol/l) or pretreated preparations with aspirin, indomethacin (10 micromol/l) or L-NAME (1 mmol/l). However, the relaxation effects of BDPBI were blocked if the preparations were pretreated with diphenhydramine (10 micromol/l) or chloropheniramine maleate (10 micromol/l). In contrast to lower concentrations of atropine (1 micromol/l), higher concentrations of atropine (30 micromol/l) did block the effects of BDPBI on the PHE-precontracted aortic rings. HTMT dimaleate (0.01-10 micromol/l), a histamine H(1) receptor agonist, also elicited relaxation effects on the PHE-precontracted preparation, and the effects were blocked if the preparations were pretreated with diphenhydramine or chloropheniramine maleate. On isolated denuded aorta of the guinea pig, BDPBI did not elicit relaxation effects on the PHE-precontracted aortic rings. These results demonstrated that the vasorelaxation effect of BDPBI on PHE-precontracted aortic rings is partly dependent on the activation of a histaminergic receptor from the vascular endothelium. We suggested that BDPBI would be an effective vasorelaxant for cardiovascular systems.
在豚鼠离体含内皮或去内皮的主动脉上测试了BDPBI（7-溴-1,4-二氢-2-苯基-4,4-双（4-吡啶基甲基）-2H-异喹啉-3-酮二盐酸盐）的药理作用。BDPBI的分子式为C(27)H(24)BrCl(2)N(3)O，以3-异苯并二氢吡喃酮为起始原料合成。在主动脉环的含内皮制剂中，去氧肾上腺素（PHE；10微摩尔/升）引起收缩，乙酰胆碱（ACh；10微摩尔/升）或BDPBI（0.01 - 10微摩尔/升）对PHE预收缩的制剂产生舒张作用。在存在肾上腺素能阻滞剂（普萘洛尔或育亨宾；1微摩尔/升）或用阿司匹林、吲哚美辛（10微摩尔/升）或L-精氨酸甲酯（1毫摩尔/升）预处理的制剂中，BDPBI对PHE预收缩主动脉环的作用未改变。然而，如果制剂用苯海拉明（10微摩尔/升）或马来酸氯苯那敏（10微摩尔/升）预处理，BDPBI的舒张作用会被阻断。与低浓度阿托品（1微摩尔/升）相反，高浓度阿托品（30微摩尔/升）确实会阻断BDPBI对PHE预收缩主动脉环的作用。组胺H(1)受体激动剂马来酸HTMT（0.01 - 10微摩尔/升）对PHE预收缩的制剂也产生舒张作用，如果制剂用苯海拉明或马来酸氯苯那敏预处理，该作用会被阻断。在豚鼠离体去内皮的主动脉上，BDPBI对PHE预收缩的主动脉环未产生舒张作用。这些结果表明，BDPBI对PHE预收缩主动脉环的血管舒张作用部分依赖于血管内皮组胺能受体的激活。我们认为BDPBI对心血管系统将是一种有效的血管舒张剂。
