Effect of amantadine on oxymorphone-induced thermal antinociception in cats

This study examined the effect of amantadine, an N-methyl-d-aspartate receptor antagonist, on the thermal antinociceptive effect of oxymorphone in cats. Six adult healthy cats were used. After baseline thermal threshold determinations, oxymorphone was administered intravenously to maintain plasma oxymorphone concentrations of 10, 20, 50, 100, 200, and 400ng/mL. In addition, amantadine, or an equivalent volume of saline, was administered intravenously to maintain a plasma amantadine concentration of 1100ng/mL. Thermal threshold and plasma oxymorphone and amantadine concentrations were determined at each target plasma oxymorphone concentration. Effect maximum models were fitted to the oxymorphone concentration-thermal threshold data, after transformation in % maximum response. Oxymorphone increased skin temperature, thermal threshold, and thermal excursion (i.e., the difference between thermal threshold and skin temperature) in a concentration-dependent manner. No significant difference was found between the amantadine and saline treatments. Mean±SE oxymorphone EC ₅₀ were 14.2±1.2 and 24.2±7.4ng/mL in the amantadine and saline groups, respectively. These values were not significantly different. Large differences in oxymorphone EC ₅₀ in the saline and amantadine treatment groups were observed in two cats. These results suggest that amantadine may decrease the antinociceptive dose of oxymorphone in some, but not all, cats.