Sa. Joneshumble et al., BW-1370U87, A NEW MONOAMINE OXIDASE-A INHIBITOR - EFFECTS ON BIOGENIC-AMINE NEUROTRANSMITTER AND METABOLITE LEVELS IN RAT-BRAIN, Drug development research, 25(3), 1992, pp. 201-207
Monoamine oxidase (MAO) inhibitors increase brain concentrations of bi
ogenic amines and decrease concentrations of the acidic metabolites of
biogenic amines. It has been suggested that the magnitude of these ef
fects is an indicator of MAO inhibition. Oral doses of BW 1370U87, moc
lobemide, and brofaromine were given to rats at doses previously shown
to induce brain MAO-A inhibition by at least 80%. The effects on brai
n biogenic amines and their metabolites were quantified 2 and 4 hr aft
er oral dosing using HPLC with electrochemical detection. Moclobemide
and BW 1370U87 induced larger increases in 5HT, NE, and DA and larger
decreases in DOPAC, 5HIAA, and HVA than did brofaromine at the doses t
ested. At 8 hr post-dose the effects of BW 1370U87 on 5HT, NE, DOPAC,
and HVA were still significant (P less-than-or-equal-to 0.05), and the
time course was similar to that seen following moclobemide and brofar
omine treatment. Only BW 1370U87 increased brain concentrations ot bio
genic amines at a dose that does not significantly potentiate pressor
effects of orally administered tyramine.