Urinary excretion of O-methylated catecholamines, tyramine and phenyl-ethylamine by volunteers treated with tranylcypromine and CGP 11305 A.
To assess the effect of the new, selective, reversible MAO A inhibitor, CGP 11305 A (4-(5-methoxy-7-bromo-benzofuranyl-2-)piperidine HCl), on MAO A and B activity in man, the daily excretion of total normetanephrine (NMN), metanephrine (MN), 3-methoxytyramine (3-MT) and beta-phenylethylamine (PEA) was measured in the urine of healthy volunteers treated with weekly increasing doses from 40 to 150 mg/d. A similar study was carried out with tranylcypromine in weekly increasing doses from 10 to 25 mg/d. Both compounds increased the excretion of NMN; with CGP 11305 A, a plateau was obtained at 50 mg/d, and tranylcypromine 20 mg was more effective than 10 mg, and was also more active than the highest dose of CGP 11305 A. Increases in MN and 3-MT produced by the latter compound were comparable to that in NMN, whereas tranylcypromine had a biphasic effect on MN excretion, and caused only a small increase in 3-MT excretion. CGP 11305 A up to 150 mg/d did not alter total tyramine excretion, whereas tranylcypromine at 20 mg caused a definite increase. Tranylcypromine led to 4-6 fold increases in PEA output at 20 and 25 mg/d, but not at 10 mg. No such effect could be demonstrated for CGP 11305 A up to 150 mg/d. These results suggest that in man MAO A was inhibited by CGP 11305 A in daily dose of 40 mg or more, whereas it did not affect MAO B at up to 150 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000661:Amphetamine / Q000652:urine; D004837:Epinephrine / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000652:urine*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009647:Normetanephrine / Q000652:urine*; D010627:Phenethylamines / Q000652:urine*; D010880:Piperidines / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology*; D014439:Tyramine / Q000652:urine*
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D010880:Piperidines; D009647:Normetanephrine; D014191:Tranylcypromine; D008676:Metanephrine; C038213:brofaromine; D000661:Amphetamine; D014439:Tyramine; D004837:Epinephrine