Elevated striatal dopamine levels following administration of D-DOPA and its alpha-keto acid metabolite DHPPA: behavioral and physiological studies in vivo in the rat.
The D stereoisomer of dihydroxyphenylalanine (D-DOPA) and its alpha-keto acid metabolite 3,4-dihydroxyphenylpyruvic acid (DHPPA) when infused into the striatum, significantly increased in vivo extracellular dopamine levels. Following D-DOPA administration, the cumulative increase in dopamine levels was 30% of the increase following L-DOPA: following DHPPA it was 11% that of L-DOPA. Rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra demonstrated brisk contralateral turning following each compound. The turning, however, was delayed by 10-20 min and total turning was 40% less following D-DOPA and 57% less following DHPPA than it was following L-DOPA. These data indicate that exogenously administered D-DOPA can be metabolized in vivo within the brain to dopamine and suggest this may occur via a transamination pathway in which DHPPA is an intermediary metabolite. The possible relevance of these findings to the treatment of Parkinson's disease is discussed.
Brannan
T
T
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Prikhojan
A
A
Yahr
M D
MD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010667:Phenylpyruvic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D015259:Dopamine Agents; D010667:Phenylpyruvic Acids; C019344:3,4-dihydroxyphenylpyruvic acid; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D004298:Dopamine