Blood pressure and heart rate response evoked by p-hydroxyamphetamine and by p-hydroxynorephedrine II. A quantitative assessment of the role of amphetamine metabolites in acute responses evoked by d-amphetamine.
At postganglionic sympathetic sites, p-hydroxyamphetamine is neither a receptor agonist nor a receptor antagonist; in addition the drug does not act presynaptically to antagonize or synergize d-amphetamine. p-Hydroxyamphetamine is an indirectly acting sympathomimetic amine with a potency approximately twice that of d-amphetamine. In the rat, a large fraction (approximately 0.5) of d-amphetamine is biotransformed to p-hydroxyamphetamine. However, the rate of biotransformation to p-hydroxyamphetamine (approximately 0.0099 . min-1) is slow compared to the rate of elimination of p-hydroxyamphetamine (0.049 . min-1). As a result, plasma levels of d-amphetamine exceed those of p-hydroxyamphetamine. The kinetic data suggest that: 1) p-hydroxyamphetamine plays little role in immediate responses to single injections of d-amphetamine; 2) p-hydroxyamphetamine is not involved in tachyphylactic responses to repeated injections of d-amphetamine; and 3) p-hydroxynorephedrine plays no role in immediate or tachyphylactic responses to d-amphetamine.
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects*; D003913:Dextroamphetamine / Q000378:metabolism / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D010665:Phenylpropanolamine / Q000031:analogs & derivatives*; D051381:Rats; D010136:p-Hydroxyamphetamine / Q000494:pharmacology*; D010137:p-Hydroxynorephedrine / Q000494:pharmacology*
D000662:Amphetamines; D010665:Phenylpropanolamine; D010137:p-Hydroxynorephedrine; D010136:p-Hydroxyamphetamine; D003913:Dextroamphetamine