期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 553, 期 1-3, 页码 82-88出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2006.09.019
关键词
presynaptic; calcium channel; analgesia; anticonvulsant; anxiolytic; transmitter release
Pregabalin, ((S)-3-(aminomethyl)-5-methylhexanoic acid, also known as (S)-3-isobutyl GABA, Lyrica (TM)) is approved for treatment of certain types of peripheral neuropathic pain and as an adjunctive therapy for partial seizures of epilepsy both the EU and the USA and also for generalized anxiety disorder in the EU. Though pregabalin binds selectively to the alpha(2)-delta (alpha(2)-delta) auxiliary subunit of voltage-gated calcium channels, the cellular details of pregabalin action are unclear. The high density Of alpha(2)-delta in skeletal muscle fibers raises the question of whether pregabalin alters excitation-contraction coupling. We used the mouse soleus neuromuscular junction from mice containing an artificially mutated alpha(2)-delta Type I protein (R217A) as a model to examine the effect of pregabalin. Pregabalin reduced nerve-evoked muscle contractions by 16% at a clinically relevant concentration of 10 mu M in wildtype mice. When acetylcholine receptors were blocked with curate, pregabalin had no effect on contraction from direct stimulation of muscle, suggesting a lack of drug effects on contraction coupling. Our data are consistent with pregabalin having no effect on striated muscle L-type calcium channel function. However, in mice expressing mutant (R217A) alpha(2)-delta Type 1, there was no significant effect of pregabalin on nerve-evoked muscle contraction. We propose that pregabalin reduces presynaptic neurotransmitter release without altering postsynaptic receptors or contraction coupling and that these effects require high affinity binding to alpha(2)-delta Type I auxiliary subunit of presynaptic voltage-gated calcium channels. (c) 2006 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据