Abstract
The effects of ifenprodil on respiratory activity in both the presence and absence of cyanide were examined using guinea pig brain mitochondria and mouse brain cytochrome oxidase preparations. Ifenprodil stimulated respiratory activity, exhibiting maximal effect at a concentration of 0.8 m m in the presence of succinate and potassium phosphate ( P i) among the various substrates, anions, and phosphonate compounds tested. The stimulatory action of ifenprodil on respiration could not be observed with frozen and thawed brain mitochondria. The stimulatory action was not affected by oligomycin but was reduced markedly by mersalyl. Dinitrophenol and flufenamic acid did not require the presence of P i for their stimulatory action on respiration. Ifenprodil abolished completely the cyanide-induced inhibition of respiration with succinate as a substrate, but elicited no significant effects against the cyanide-induced inhibition of cytochrome oxidase activity in both in vivo and in vitro experiments. The results suggest that ifenprodil seems to act on the mitochondrial membrane by accelerating P i and succinic acid transport through the membrane as well as by stimulating succinate oxidation, and that these stimulatory actions of ifenprodil may be involved in its protective effects against cyanide toxicity.
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