title: Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and carbidopa.
abstract: 1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase in rat and mouse liver. This results in reduced synthesis of nicotinamide coenzymes from tryptophan, and hence an increased reliance on dietary niacin. 2. Pellagra might be expected as a result of this inhibition of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug. 3. The urinary excretion of N1-methyl-nicotinamide, a product of nicotinamide nucleotide metabolism, is considerably reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. This means that many of these patients could be classified as 'at risk' of niacin deficiency, even if not frankly deficient. 4. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, also show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.
mesh_terms: D000293:Adolescent; D000328:Adult; D001545:Benserazide / Q000627:therapeutic use*; D001971:Bromocriptine / Q000627:therapeutic use; D002230:Carbidopa / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use*; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008837:Micrococcus / Q000201:enzymology; D008875:Middle Aged; D009535:Nicotinamidase / Q000378:metabolism; D009539:Nicotinic Acids / Q000172:deficiency*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D006834:Hydrazines; D009539:Nicotinic Acids; D001971:Bromocriptine; D007980:Levodopa; D001545:Benserazide; D014364:Tryptophan; D009535:Nicotinamidase; D002230:Carbidopa