The effects of the clinically tested NMDA receptor antagonist memantine on carrageenan-induced thermal hyperalgesia in rats.
This study tested the prophylactic and the therapeutic efficacy of memantine (1-amino-3,5-dimethyl-amandate), a clinically tested N-methyl-D-aspartate (NMDA) receptor antagonist, in suppressing carrageenan-induced thermal hyperalgesia in rats. Rats were injected with 0.1 ml of 1% carrageenan solution s.c. into the right hindpaw, and exhibited hyperalgesia in the injected paw as evidenced by a significant reduction of withdrawal latencies from baseline 1, 3, 5, and 24 h following carrageenan. Prophylactic injection of memantine, 10 and 15 mg/kg, significantly suppressed the hyperalgesia 1, 3, and 5 h post-carrageenan, with maximal effects of 70% (10 mg/kg) and 90% (15 mg/kg) at 1 h post-carrageenan. Therapeutic injection of 10 mg/kg of memantine (2.5 h post-carrageenan) had no effect. The 15 mg/kg dose produced a small effect (peak of 44%) at 3.5 h but not at a statistically significant level, and had no effect 5 h post-carrageenan. This study provides evidence that memantine produces primarily a prophylactic effect (and has only a tendency to produce a therapeutic effect) on carrageenan-induced hyperalgesia at doses that do not significantly alter other motor behaviors.
Eisenberg
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Department of Neurology, Massachusetts General Hospital, Boston 02129.
LaCross
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Strassman
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D002351:Carrageenan; D008559:Memantine