Formation of alpha-methyldopamine ("Catecholamphetamine") from p-hydroxyamphetamine by rat brain microsomes.
Amphetamine is a sympathomimetic and psychotropic drug which is extensively metabolized in liver and in brain. One of its major metabolites, p-hydroxyamphetamine, is accumulated by cortical and striatal synaptosomes. In order to learn whether p-hydroxyamphetamine can be further metabolized to a catecholamine, a sensitive radioenzymatic assay was developed which couples the formation of the "catecholamphetamine" to rapid O-methylation by catechol-O-methyltransferase in the presence of [3H]-methyl-S-adenosylmethionine. Rat brain microsomes contain a cytochrome P-450-dependent monooxygenase which synthesizes catecholamphetamine from p-hydroxyamphetamine. The formation of this catechol metabolite may be involved in the development of tolerance in chronic amphetamine use.
D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002396:Catechols / Q000378:metabolism; D003846:Deoxyepinephrine / Q000378:metabolism* / Q000031:analogs & derivatives; D004298:Dopamine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D051381:Rats; D010136:p-Hydroxyamphetamine / Q000378:metabolism*
D000662:Amphetamines; D002396:Catechols; C023492:alpha-methyldopamine; D002394:Catechol O-Methyltransferase; D010136:p-Hydroxyamphetamine; D003846:Deoxyepinephrine; D004298:Dopamine