EFFECTS OF L-DOPA CARBIDOPA ADMINISTRATION ON THE LEVELS OF L-DOPA, OTHER AMINO-ACIDS AND RELATED-COMPOUNDS IN THE PLASMA, BRAIN AND HEART OF THE RAT/

Rats were treated intraperitoneally with a mixture of 250 mg/kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. P lasma, heart and cortex, midbrain, brainstem and cerebellum were remov ed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased fr om undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino com pounds were significantly affected by L-DOPA/carbidopa (p less than or equal to 0.01). Plasma concentrations of phosphoserine, oxidized glut athione, citrulline, phenylalanine, tyrosine and l-methylhistidine inc reased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threon ine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, carnosine and homocarno sine increased. In the midbrain, valine increased and leucine, ornithi ne and oxidized glutathione decreased. In the cerebellum, citrulline i ncreased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem , arginine was slightly decreased with a concomitant increase in citru lline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed c hanges in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of P arkinson's disease.