Reference

Antidystonic effects of Kv7 (KCNQ) channel openers in the dtsz mutant, an animal model of primary paroxysmal dystonia

All Rights Reserved. Antidystonic effects of Kv7 (KCNQ) channel openers in the dtsz mutant, an animal model of primary paroxysmal dystonia. Richter, A.; Sander, S. E.; Rundfeldt, C. (Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universitaet Berlin, Berlin 14195, Germany). British Journal of Pharmacology, 149(6), 747-753 (English) 2006 Nature Publishing Group. CODEN: BJPCBM. ISSN: 0007-1188. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Mutations in neuronal Kv7 (KCNQ) potassium channels can cause episodic neurol. disorders. The role of Kv7 channels in the pathogenesis and as targets for the treatment of paroxysmal dyskinesias with dystonia have so far not been examd. In the present study, the authors therefore examd. the effects of the activators of neuronal Kv7.2/7.There are some reagents with their cas registry numbers 56995-20-1 and 150812-12-7 are used in this study.3 channels retigabine (5, 7.5, 10 mg kg-1 i.p. and 10, 20 mg kg-1 p.o.) and flupirtine (10, 20 mg kg-1 i.p.) and of the channel blocker 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991, 3 and 6 mg kg-1 i.p.) in the dtsz mutant hamster, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress. Retigabine (10 mg kg-1 i.p., 20 mg kg-1 p.o.) and flupirtine (20 mg kg-1 i.p.) significantly improved dystonia, while XE-991 caused a significant aggravation in the dtsz mutant. The antidystonic effect of retigabine (10 mg kg-1 i.p.) was counteracted by XE-991 (3 mg kg-1 i.p.). These data indicate that dysfunctions of neuronal Kv7 channels deserve attention in dyskinesias. Since retigabine and flupirtine are well tolerated in humans, the present finding of pronounced antidystonic efficacy in the dtsz mutant suggests that neuronal Kv7 channel activators are interesting candidates for the treatment of dystonia-assocd. dyskinesias and probably of other types of dystonias. The established analgesic effects of Kv7 channel openers might contribute to improvement of these disorders which are often accompanied by painful muscle spasms. .