Antidystonic effects of the NMDA receptor antagonists memantine, MK-801 and CGP 37849 in a mutant hamster model of paroxysmal dystonia.
The effects of competitive and noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists were evaluated in an inbred line of Syrian golden hamsters, in which sustained dystonic postures of limbs and trunk can be initiated by handling or mild environmental stimuli. In this model of paroxysmal dystonia, the noncompetitive NMDA receptor antagonists memantine and MK-801 (dizocilpine) delayed the progression of dystonic attacks in a dose-dependent fashion. The novel competitive NMDA receptor antagonist CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) was more effective than memantine and MK-801, because it retarded not only the progression but also reduced the severity of the dystonic movements. All compounds exhibited antidystonic effects at doses which did not cause marked ataxia or sedation. The data indicate that NMDA receptor antagonists might be interesting candidates for treatment of dystonia.
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, F.R.G.
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A
Richter
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G
Fredow
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W
Löscher
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D006224:Cricetinae; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000188:drug therapy*; D005260:Female; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D008647:Mesocricetus; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D008559:Memantine