Gabapentin decreases the severity of dystonia at low doses in a genetic animal model of paroxysmal dystonic choreoathetosis.
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.
Richter
A
A
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany. arichter@pharma.tiho-hannover.de
Löscher
W
W
D000085:Acetates / Q000627:therapeutic use*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D006224:Cricetinae; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D000077206:Gabapentin; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin