In vivo evidence for the reversible action of the monoamine oxidase inhibitor brofaromine on 5-hydroxytryptamine release in rat brain.
We have used intracerebral microdialysis to examine the reversibility of the action of brofaromine, a selective inhibitor of monoamine oxidase-A (MAO, E.C. 1.4.3.4.), on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) output in rat frontal cortex. Brofaromine significantly increased the 5-HT output to about 200% of basal values 4 h after the s.c. administration of 10 and 30 mg/kg (but not 3 mg/kg) and reduced the concentration of 5-HIAA in the dialysate dose-dependently (61%, 53% and 41% of basal value with doses of 3, 10 and 30 mg/kg, respectively). At this time, cortical 5-HT concentration was increased and cortical 5-HIAA concentration was decreased in a dose-dependent manner. Treatment of rats with 10 mg/kg brofaromine plus 2.5 mg/kg of the irreversible MAO-B inhibitor L-deprenyl increased the concentration of 5-HT in the dialysate more than did brofaromine alone (503% vs 206% of the basal value, 4h after administration). Similarly, clorgyline (5 mg/kg) plus L-deprenyl (2.5 mg/kg) increased the concentration of 5-HT in the dialysate to 461% of the control value. This indicates that the concurrent inhibition of both types of MAO increases 5-HT output more than the selective blockade of either enzyme subtype. We have used this characteristic to examine, in vivo, the reversibility of the interaction of brofaromine with MAO-A. The output of 5-HT and 5-HIAA was examined 19-21 h after treatment with L-deprenyl plus clorgyline or L-deprenyl plus brofaromine.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Neurochemistry, Centro de Investigación y Desarrollo, Barcelona, Spain.
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D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C038213:brofaromine