在阵发性肌张力障碍性舞蹈手足徐动症的基因动物模型中，加巴喷丁在低剂量时可降低肌张力障碍的严重程度。

Gabapentin decreases the severity of dystonia at low doses in a genetic animal model of paroxysmal dystonic choreoathetosis.

作者信息

Richter A, Löscher W

机构信息

Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.

出版信息

Eur J Pharmacol. 1999 Mar 26;369(3):335-8. doi: 10.1016/s0014-2999(99)00104-1.

DOI:10.1016/s0014-2999(99)00104-1

PMID:10225372

Abstract

The effects of the gamma-aminobutyric acid (GABA)-potentiating drug gabapentin (1-(aminomethyl) cyclohexaneacetic acid) on severity of dystonia were examined in a hamster model of idiopathic paroxysmal dystonic choreoathetosis. In the genetically dystonic hamster (dt(sz)) recent pharmacological and neurochemical studies suggested that disturbed GABAergic inhibition is involved in the pathogenesis. In line with a case report of beneficial effects in human paroxysmal dystonic choreoathetosis, gabapentin reduced the severity of dystonia in mutant hamsters at doses of 5 and 10 mg kg(-1) i.p. At higher doses (20 and 100 mg kg(-1)), gabapentin, however, failed to exert antidystonic effects. The GABApotentiating activity of gabapentin could explain the antidystonic effects of low doses, while the loss of efficacy at higher doses may be due to other mechanisms of gabapentin.

摘要

在特发性阵发性肌张力障碍性舞蹈手足徐动症的仓鼠模型中，研究了γ-氨基丁酸（GABA）增强药物加巴喷丁（1-(氨甲基)环己烷乙酸）对肌张力障碍严重程度的影响。在遗传性肌张力障碍仓鼠（dt(sz)）中，最近的药理学和神经化学研究表明，GABA能抑制紊乱参与了发病机制。与人类阵发性肌张力障碍性舞蹈手足徐动症有益效果的病例报告一致，加巴喷丁腹腔注射剂量为5和10 mg kg(-1)时可降低突变仓鼠肌张力障碍的严重程度。然而，在更高剂量（20和100 mg kg(-1)）时，加巴喷丁未能发挥抗肌张力障碍作用。加巴喷丁的GABA增强活性可以解释低剂量的抗肌张力障碍作用，而高剂量时疗效丧失可能归因于加巴喷丁的其他机制。