Antidystonic effects of L-type Ca2+ channel antagonists in a hamster model of idiopathic dystonia.
The effects of selective L-type Ca2+ channel antagonists on severity of dystonia were investigated in a mutant hamster model of idiopathic generalized dystonia. Nimodipine and diltiazem significantly decreased the severity of dystonia. Nimodipine was more potent in this respect and did not cause any behavioral side effects. The present data therefore suggest that Ca2+ channel antagonists could be useful in the treatment of idiopathic dystonia. The antidystonic effect of diltiazem and nimodipine may be based on their antidopaminergic action. However, the lack of significant effects of the L-type channel agonist (+/-)-BAY k-8644 (1-5 mg/kg; methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl) -pyridine-5-carboxylate)) on severity of dystonia may indicate that voltage-gated Ca2+ channels are not critically involved in the pathophysiology of dystonia in mutant hamsters.
Richter
A
A
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Löscher
W
W
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006224:Cricetinae; D004110:Diltiazem / Q000494:pharmacology*; D004421:Dystonia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004110:Diltiazem