BW-1370U87, A NEW MONOAMINE OXIDASE-A INHIBITOR - EFFECTS ON BIOGENIC-AMINE NEUROTRANSMITTER AND METABOLITE LEVELS IN RAT-BRAIN

Citation
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
Citations number
15
Journal title
ISSN journal
02724391
Volume
25
Issue
3
Year of publication
1992
Pages
201 - 207
Database
ISI
SICI code
0272-4391(1992)25:3<201:BANMOI>2.0.ZU;2-V
Abstract
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.