The depletion of rat cortical norepinephrine and the inhibition of [3H]norepinephrine uptake by xylamine does not require monoamine oxidase activity.
Inhibition of monoamine oxidase A through pretreatment of rats with clorgyline (10 mg/kg ip) or the pro-drug MDL 72,394 (0.5 mg/kg ip) did not block the amine-depleting action of xylamine (25 mg/kg ip). Xylamine treatment resulted in a loss of approximately 60% of the control level of norepinephrine in the cerebral cortex. A 1-hr pretreatment, but not a 24-hr pretreatment, with the monoamine oxidase B inhibitor, L-deprenyl (10 mg/kg ip), prevented the depletion of norepinephrine by xylamine. In addition, pretreatment with MDL 72,974 (1.25 mg/kg ip), a monoamine oxidase B inhibitor without amine-releasing or uptake - inhibiting effects, did not protect cortical norepinephrine levels. Inhibition of monoamine oxidase by either MDL 72,974 or MDL 72,394 did not prevent the inhibition of [3H]norepinephrine uptake into rat cortical synaptosomes by xylamine. These data indicate that monoamine oxidase does not mediate the amine-releasing or uptake inhibiting properties of xylamine. The protection afforded by L-deprenyl following a 1-hr pretreatment most probably was due to accumulation of its metabolite, L-amphetamine, which would inhibit the uptake carrier. A functional carrier is required for depletion since desipramine (20 mg/kg ip) administered 1 hr prior to xylamine, was also able to prevent depletion of norepinephrine.
D000498:Allyl Compounds; D000818:Animals; D002082:Butylamines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000498:Allyl Compounds; D002082:Butylamines; D008996:Monoamine Oxidase Inhibitors; D009588:Nitrogen Mustard Compounds; C058000:mofegiline; D012642:Selegiline; D014443:Tyrosine; C026131:xylamine; C046880:beta-fluoromethylene-3-tyrosine; D008995:Monoamine Oxidase; D003010:Clorgyline; D003891:Desipramine; D009638:Norepinephrine