鉀通道開放劑治療中風(fēng)
BMS-204352 (MaxiPost), 一種鉀通道開放劑,，在腦卒中局部缺血時(shí)減少鈣離子損傷性向神經(jīng)細(xì)胞流入，從而在一定程度減輕了腦部損傷,。
在自然醫(yī)學(xué)四月刊的一份研究報(bào)告中，來(lái)自美國(guó)康涅狄格州WallingfordBristol-Myers Squibb 藥物研究所的Dr. Valentin K. Gribkoff和同事表明,，在腦局部缺血時(shí),，神經(jīng)細(xì)胞內(nèi)鈣離子濃度呈病理性增高，而鉀通道開放劑可調(diào)節(jié)此內(nèi)源性系統(tǒng)以平衡鈣流量,。
研究者進(jìn)行了測(cè)試化合物BMS-204352對(duì)腦卒中效用的鼠實(shí)驗(yàn),。試驗(yàn)鼠在重度腦血管栓塞后2小時(shí)給BMS-204352，其腦部損傷明顯小于對(duì)照組,。而且BMS-204352并不影響試驗(yàn)鼠血壓和腦部血流,。
“動(dòng)物腦卒中模型不能預(yù)測(cè)臨床效果，所以前瞻性評(píng)估尚不可能,。”研究者指出,，“雖然我們集中在與人類急性腦卒中有共性的模型上，我們也想驗(yàn)證這樣的假說(shuō),，即腦部鉀通道開放劑直接給藥在鼠腦卒中模型中是有效的,。”
Dr. Gribkoff的研究組相信，如果BMS-204352對(duì)鉀通道有特異性和對(duì)鈣產(chǎn)生敏感,，對(duì)沒(méi)有缺血的腦細(xì)胞無(wú)作用,。”BMS-204352現(xiàn)已進(jìn)入臨床試驗(yàn)。
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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