The acute effect of the bioprecursor of the selective brain MAO-A inhibitor, MDL 72392, on rat pineal melatonin biosynthesis.
The bioprecursor amino acid MDL 72394 is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to liberate MDL 72392, an irreversible selective MAO-A inhibitor. Pretreatment with the AADC inhibitor carbidopa, which does not penetrate the brain-blood barrier, prevents the liberation of the MAO-A inhibitor outside the brain and results in exclusive inhibition of brain MAO-A. We found that systemic administration of MDL 72394 (0.5 mg/kg, i.p.) stimulated rat pineal melatonin biosynthesis. Carbidopa, in a dose-dependent manner, attenuated or completely prevented MDL-induced stimulation of melatonin biosynthesis in the pineal gland located outside the blood-brain-barrier.
Oxenkrug
G F
GF
Psychiatry Service, VAMC, Providence, RI 02908.
Requintina
P J
PJ
Yuwiler
A
A
Palfreyman
M G
MG
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010870:Pineal Gland / Q000378:metabolism*; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D011355:Prodrugs; C079104:(E)-beta-fluoromethylene-m-tyramine; D008995:Monoamine Oxidase; D008550:Melatonin; D002230:Carbidopa; D014439:Tyramine