钾通道开放剂治疗中风
BMS-204352 (MaxiPost), 一种钾通道开放剂，在脑卒中局部缺血时减少钙离子损伤性向神经细胞流入，从而在一定程度减轻了脑部损伤。
在自然医学四月刊的一份研究报告中，来自美国康涅狄格州WallingfordBristol-Myers Squibb 药物研究所的Dr. Valentin K. Gribkoff和同事表明，在脑局部缺血时，神经细胞内钙离子浓度呈病理性增高，而钾通道开放剂可调节此内源性系统以平衡钙流量。
研究者进行了测试化合物BMS-204352对脑卒中效用的鼠实验。试验鼠在重度脑血管栓塞后2小时给BMS-204352，其脑部损伤明显小于对照组。而且BMS-204352并不影响试验鼠血压和脑部血流。
“动物脑卒中模型不能预测临床效果，所以前瞻性评估尚不可能。”研究者指出，“虽然我们集中在与人类急性脑卒中有共性的模型上，我们也想验证这样的假说，即脑部钾通道开放剂直接给药在鼠脑卒中模型中是有效的。”
Dr. Gribkoff的研究组相信，如果BMS-204352对钾通道有特异性和对钙产生敏感，对没有缺血的脑细胞无作用。”BMS-204352现已进入临床试验。
Potassium channel opener shows promise in treatment of stroke
Last Updated: 2001-04-02 15:20:37 EDT (Reuters Health)
WESTPORT, CT (Reuters Health) - BMS-204352 (MaxiPost), a potassium channel-opening drug, appears to limit the amount of brain damage that occurs after a stroke by reducing the harmful influx of calcium into neurons after ischemic insult.
In a study reported in the April issue of Nature Medicine, Dr. Valentin K. Gribkoff and colleagues from the Bristol-Myers Squibb Pharmaceutical Research Institute in Wallingford, Connecticut, note that during ischemia, neurons are exposed to "pathologically high levels of intracellular calcium." Openers of calcium-activated maxi-potassium channels should modulate the endogenous system for regulating calcium influx.
The researchers tested the efficacy of one such compound, BMS-204352, in a rat model of ischemic stroke. Rats treated with BMS-204352 two hours after major cerebral artery occlusion showed significantly less cerebral damage than similar animals that did not receive this therapy, the authors note. Furthermore, BMS-204352 did not affect the animal's blood pressure or cerebral blood flow.
"Animal models of stroke have not yet predicted clinical efficacy, so predictive validation of particular models is not yet possible," the researchers point out. "Although we concentrated on models with some common features of acute stroke in humans, our purpose was to test the hypothesis that a centrally available maxi-potassium channel opener was active in rat stroke models."
Dr. Gribkoff's team believes that "given the characteristics of the maxi-potassium channel and the novel calcium sensitivity of BMS-204352, this compound should have little effect on the function of non-ischemic cells." BMS-204352 is currently undergoing clinical trials in subjects with suspected acute stroke.
Nat Med 2001;7:471-477.
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