Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian rat.
D-3,4-Dihydroxyphenylalanine (D-dopa) and L-3,4-dihydroxyphenylalanine (L-dopa) induced circling in rats with a unilateral 6-hydroxydopamine lesion of substantia nigra with similar potency. D-Dopa is not a substrate for aromatic L-amino acid decarboxylase, the enzyme which metabolizes L-dopa to dopamine. This raises the question of how D-dopa has behavioral effect. Two pathways have been suggested to result in conversion of D-dopa to L-dopa, one involving oxidation of D-dopa to dihydroxyphenylpyruvic acid (DHPPA) by D-amino acid oxidase, the other involving transamination of D-dopa to DHPPA. Here we show that sodium benzoate, an inhibitor of D-amino acid oxidase, blocks D-dopa-induced circling while having no effect on circling induced by L-dopa. The results suggest that conversion of D-dopa to L-dopa via DHPPA is highly dependent on oxidase activity and that sodium benzoate effectively inhibits this process in vivo in rat.
Moses
J
J
Department of Psychiatry and Behavioral Sciences, University of Texas, Health Science Center, Houston 77030-3419, USA.
Siddiqui
A
A
Silverman
P B
PB
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology*; D019817:Benzoic Acid; D002230:Carbidopa / Q000494:pharmacology; D005260:Female; D005520:Food Preservatives / Q000494:pharmacology*; D007980:Levodopa / Q000009:adverse effects* / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D010667:Phenylpyruvic Acids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000978:Antiparkinson Agents; D001565:Benzoates; D005520:Food Preservatives; D010667:Phenylpyruvic Acids; C019344:3,4-dihydroxyphenylpyruvic acid; D007980:Levodopa; D019817:Benzoic Acid; D000594:Amino Acid Oxidoreductases; D002230:Carbidopa