Effects of a monoamine oxidase A inhibitor, FLA 668 (+) on the adrenergic mechanisms of the dog saphenous vein.
FLA 668 (+) [(S)-(+)-4-amino-2, alpha-dimethylethylphenethylamine (+)-hydrogen bitartrate] selectively inhibited MAO type A in homogenates of dog saphenous vein, with a IC50 of 1 mumol/l for MAO A and greater than 1 mmol/l for MAO B. At concentrations of 1 mumol/l and higher, FLA 668(+) progressively decreased the formation of deaminated metabolites by saphenous vein strips incubated with 3H-noradrenaline, with a preferential action on DOPEG formation. Normetanephrine formation increased but this increase did not wholly compensate for the reduction in the formation of deaminated metabolites. FLA 668(+) caused increased reactivity of saphenous vein strips to noradrenaline and markedly reduced the accumulation of 3H-noradrenaline in the incubated tissue; both effects were still evident in the presence of clorgyline. After cocaine, FLA 668(+) caused no further increase in sensitivity. It is concluded that FLA 668(+) is, in the saphenous vein of the dog, a selective inhibitor of MAO type A and that it exerts a cocaine-like effect.
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D012501:Saphenous Vein / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D010627:Phenethylamines; C047814:4-amino-2,alpha-dimethylethylphenethylamine; D003042:Cocaine; D003010:Clorgyline; D009638:Norepinephrine