Effects of T-type calcium channel blockers on a parkinsonian tremor model in rats
Effects of T-type calcium channel blockers on a parkinsonian tremor model in rats
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DOI：
10.1016/j.pbb.2010.11.014
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Kondo, Tomoyoshi
中科院分区：
文献类型：
--
作者：
Miwa, Hideto;Koh, Jinsoo;Kondo, Tomoyoshi
t型钙通道与中枢神经系统节律性放电模式的产生密切相关。这些通道的阻滞剂可能对治疗各种类型的震颤具有治疗潜力。本研究旨在研究一系列t型钙通道阻滞剂对大鼠帕金森震颤模型的影响。我们测试了几种t型钙通道阻滞剂，包括唑尼沙胺（ZNS）、乙砜胺、洛美嗪、阿米洛胺、米贝弗拉迪和米贝弗拉迪衍生物NCC 55-0396，对他克林诱导的震颤下颌运动（TJMs）的影响，这是一种帕金森震颤动物模型。在被试药物中，只有ZNS和NCC 55-0396在非镇静剂量下显著抑制TJMs。药物对中枢神经系统（CNS）的传递性至少可以部分解释它们不同的抗tjm作用。然而，需要进一步的研究来揭示其他因素，因为尽管已知乙磺酰亚胺可以穿过血脑屏障，但未能显示出抗tjm的作用。目前的结果表明，中枢神经系统中的t型钙通道可能是开发治疗帕金森性震颤的新治疗策略的合适靶点。(C) 2010爱思唯尔公司版权所有。
T-type calcium channels are strongly associated with the generation of rhythmic firing patterns in the CNS. Blockers of these channels may have therapeutic potential for treating various types of tremor. The present study aimed to study the effects of a range of T-type calcium channel blockers in a parkinsonian tremor model in rats. We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor. Among the tested drugs, only ZNS and NCC 55-0396 significantly suppressed TJMs when given at a non-sedating dose. The transitivity of drugs to the central nervous system (CNS) may at least partially explain their differential anti-TJM effects. However, further studies are necessary to reveal other factors, since ethosuximide failed to show anti-TJM effects despite being known to cross the blood brain barrier. The present results suggest that T-type calcium channels in the CNS may be a suitable target for developing new therapeutic strategies for treating parkinsonian tremor. (C) 2010 Elsevier Inc. All rights reserved.