卡麦角林:药理学,眼部低血压的研究在多个物种,房水动态调制的猕猴猴的眼睛。
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谢里夫NA,麦克劳克林,凯莉CR, Katoli P, Drace C,侯赛因年代,Crosson C, C环面,詹GL,“真麦酒运动”组织C
卡麦角林:药理学,眼部低血压的研究在多个物种,房水动态调制的猕猴猴的眼睛。
Exp眼研究》2009年3月,88 (3):386 - 97。doi: 10.1016 / j.exer.2008.10.003。Epub 2008年11月1日。
- PubMed ID
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18992242 (在PubMed]
- 文摘
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当前研究的目的是确定在体外和体内的眼和non-ocular药理特性卡麦角林使用有据可查的受体结合,细胞功能检测,和体内模型。卡麦角林绑定到本地和/或人类克隆serotonin-2A / B / C (5 ht (2 a / B / C)), 5 ht (1)、5 ht(7),α(2 B), dopamine-2/3 (D(2/3))与摩尔亲和力的受体亚型。卡麦角林是一个在人类重组5 ht受体激动剂(2),5 ht (1 a)和D(2/3)但拮抗剂5 ht受体α(7)和(2)受体。在人类主要睫状肌(h-CM)和小梁网(h-TM)细胞,卡麦角林刺激磷酸肌醇(π)水解(EC(50) = 19在TM + / 7海里;76海里h-CM)和细胞内钙(2 +)((Ca(2 +))(我)动员(EC (50) = 570 + / h-TM -83海里;电子商务(50)= 900 + / h-CM -320海里)。Cabergoline-induced (Ca (2 +)) (i)动员h-TM h-CM细胞是由一个5 ht引起强有力地(2)选择性拮抗剂(m - 100907 K (i) = 0.29 - -0.53海里)。卡麦角林也刺激(Ca(2 +))(我)动员更有说服力地通过人类克隆5 ht (2) (EC(50) = 63.4 + / - -10.3海里)比通过5 ht (2 b)和5 ht (2 c)受体。在h-CM细胞中,卡麦角林(1 microM)刺激生产pro-matrix metalloproteinases-1和3和主体性forskolin加强营地生产。卡麦角林灌注(1 microM)通过前部分引起的猪的眼睛流出设施增加显著(27%)。 Topically administered cabergoline (300-500 microg) in Dutch-belted rabbit eyes yielded 4.5 microMM and 1.97 microM levels in the aqueous humor 30 min and 90 min post-dose but failed to modulate intraocular pressure (IOP). However, cabergoline was an efficacious IOP-lowering agent in normotensive Brown Norway rats (25% IOP decrease with 6 microg at 4h post-dose) and in conscious ocular hypertensive cynomolgus monkeys (peak reduction of 30.6+/-3.6% with 50 microg at 3h post-dose; 30.4+/-4.5% with 500 microg at 7h post-dose). In ketamine-sedated monkeys, IOP was significantly lowered at 2.5h after the second topical ocular dose (300 microg) of cabergoline by 23% (p<0.02) and 35% (p<0.004) in normotensive and ocular hypertensive eyes, respectively. In normotensive eyes, cabergoline increased uveoscleral outflow (0.69+/-0.7 microL/min-1.61+/-0.97 microL/min, n=13; p<0.01). However, only seven of the eleven ocular hypertensive monkeys showed significantly increased uveoscleral outflow. These data indicate that cabergoline's most prominent agonist activity involves activation of 5HT(2), 5HT(1A), and D(2/3) receptors. Since 5HT(1A) agonists, 5HT(7) antagonists, and alpha(2) antagonists do not lower IOP in conscious ocular hypertensive monkeys, the 5HT(2) and dopaminergic agonist activities of cabergoline probably mediated the IOP reduction observed with this compound in this species.