Catecholamine uptake inhibitors elevate 6-hydroxydopamine in brain after administration of 6-hydroxydopa.
Desipramine and nomifensine, two norepinephrine uptake blockers, elevated by 63-248% the levels of 6-hydroxydopamine found in the frontal cortex at 1-4 h after administration of 6-OH-DOPA. Nomifensine also elevated 6-hydroxydopamine by 83% in the striatum at 4 h. These results nullify prior suggestions in the literature that 6-OH-DOPA is decarboxylated to 6-hydroxydopamine mainly outside of catecholamine nerve terminals and that 6-hydroxydopamine subsequently gains access to nerve terminals via the axonal membrane transport system for catecholamines.
Evans
J
J
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029.
Cohen
G
G
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002395:Catecholamines / Q000037:antagonists & inhibitors*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003891:Desipramine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009627:Nomifensine / Q000494:pharmacology; D016627:Oxidopamine / Q000378:metabolism*
D002395:Catecholamines; D009627:Nomifensine; C001388:6-hydroxydopa; D004295:Dihydroxyphenylalanine; D016627:Oxidopamine; D003891:Desipramine