Effect of alpha-methyl fluorodopa on dopamine metabolites: importance of conjugation and egress.
The effects of D,L-alpha-monofluoromethyldopa (MFMD), an inhibitor of aromatic L-amino acid decarboxylase, on the metabolism of dopamine (DA) and 5-hydroxytryptamine was investigated using rat brain and cerebrospinal fluid (CSF). Vehicle or MFMD (100 mg/kg) was given p.o. and 16 h later probenecid (200 mg/kg i.p.). CSF was sampled and the rats killed immediately or after 1 h. Vehicle treated rats showed regional differences of percentage conjugation of DA metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC), striatum 10%, rest of brain 45%, CSF 67%; homovanillic acid (HVA), striatum 20%, rest of brain 35%, CSF 53%. These differences and the proportionately greater increases of conjugates than of free acids after probenecid vitiate regional comparisons of DA metabolism if conjugates are not included. MFMD alone decreased neither 5HIAA (except in the striatum) nor the free DA metabolites but decreased both conjugates in CSF and conjugated DOPAC in rest of brain. The inhibitory effects of MFMD on 5HT and DA synthesis were most evident when measured by the accumulation of 5HIAA or total (DOPAC + HVA) after giving probenecid. MFMD may also inhibit amine metabolite egress and the conjugation of DOPAC and HVA.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D011339:Probenecid; D004298:Dopamine; D006719:Homovanillic Acid