title: Retigabine, a K(V)7 (KCNQ) potassium channel opener, attenuates L-DOPA-induced dyskinesias in 6-OHDA-lesioned rats.
abstract: L-DOPA-induced dyskinesias (LID) represent a severe complication of long-time pharmacotherapy in Parkinson's disease that necessitates novel therapeutics. The acute and chronic effects of K(V)7.2-7.5 channel openers (retigabine, flupirtine) on the severity of LID and parkinsonian signs were examined in comparison to the glutamate receptor antagonist amantadine (positive control) in a rat model of LID. Acute treatment with retigabine (2.5, 5 mg/kg i.p.) and flupirtine (5, 10 mg/kg i.p.) significantly reduced the severity of abnormal involuntary movements (AIM) to a comparable extent as amantadine (20, 40 mg/kg s.c.), but flupirtine delayed the disappearance of AIM. Chronic treatment with retigabine (daily 5 mg/kg i.p. over 19 days combined with l-DOPA 10 mg i.p.) did not prevent or delay the development of LID, but reduced the severity of AIM, while antidyskinetic effects of amantadine (40 mg/kg i.p.) were restricted to the first day of treatment. Retigabine caused sedation and ataxia which declined during the chronic treatment, but did not reduce the antiparkinsonian effects of l-DOPA in these experiments. Acute co-injections of retigabine (5 mg) together with l-DOPA (10 mg/kg) neither reduced the motor performance in the rotarod test nor exerted negative effects on the antiparkinsonian efficacy of l-DOPA in the block and stepping test. Nevertheless, the sedative effects of retigabine may limit its therapeutic potential for the treatment of LID. The present data indicate that K(V)7 channels deserve attention in the research of the pathophysiology of dyskinesias. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors.affiliation: Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, 14195 Berlin, Germany. sander.svenja@vetmed.fu-berlin.de
authors.forename: S E
authors.initials: SE
authors.lastname: Sander
authors.forename: C
authors.initials: C
authors.lastname: Lemm
authors.forename: N
authors.initials: N
authors.lastname: Lange
authors.forename: M
authors.initials: M
authors.lastname: Hamann
authors.forename: A
authors.initials: A
authors.lastname: Richter
mesh_terms: D000547:Amantadine / Q000494:pharmacology / Q000627:therapeutic use; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine / Q000494:pharmacology; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects*
chemical_list: D000631:Aminopyridines; D000927:Anticonvulsants; D000978:Antiparkinson Agents; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine; D016627:Oxidopamine; D000547:Amantadine; C034161:flupirtine