A method for measuring monoamine turnover in animals using an irreversible inhibitor of aromatic L-amino acid decarboxylase, DL-alpha-mono fluoromethyldopa.
DL-alpha-monofluoromethyldopa (MFMD) is a potent enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase which, when given to rats or mice at 100 and 250 mg/kg i.p., respectively, causes a linear accumulation of L-DOPA and 5HTP and an exponential decline of noradrenaline, dopamine, and 5HT concentrations in the brain. Rates of change of these parameters can be used to calculate the turnover of the three principle monoamine neurotransmitters. Experiments with haloperidol (1 mg/kg s.c.) and the central 5HT agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (0.25 mg/kg s.c.), have been performed to validate the use of MFMD to measure monoamine turnover. MFMD has several advantages over classical methods for the determination of comparative turnovers using enzyme inhibitors.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives*; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001679:Biogenic Amines; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine