The enhanced daily excretion of urinary methylamine in rats treated with semicarbazide or hydralazine may be related to the inhibition of semicarbazide-sensitive amine oxidase activities.
The effects of amine oxidase inhibitors upon the daily urinary excretion of monomethylamine (MMA), dimethylamine (DMA), trimethylamine (TMA) and ammonia in the rat have been examined. Administration of hydralazine (5 mg kg-1) or semicarbazide (100 mg kg-1), drugs which irreversibly inhibit semicarbazide-sensitive amine oxidases (SSAO) but not monoamine oxidase (MAO), enhanced MMA excretion by around three- to six-fold above pretreatment levels, whereas no effect of pargyline (25 mg kg-1), a selective irreversible inhibitor of MAO was found. No apparent changes in DMA or TMA excretion in response to drug-treatment were observed. Ammonia excretion also was generally unchanged except for an apparent marked increase (approximately four-fold) over the 24 h following semicarbazide, a result which might be explained if ammonia is a degradation product of semicarbazide metabolism in the rat. With recent evidence that MMA is a substrate in-vitro for SSAO activities, results here may indicate that SSAO or related enzymes are involved in endogenous MMA turnover.
Lyles
G A
GA
Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, Scotland, UK.
McDougall
S A
SA
D000818:Animals; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D008744:Methylamines / Q000652:urine*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology*
D008744:Methylamines; D012663:Semicarbazides; D006830:Hydralazine; D010293:Pargyline; D000587:Oxidoreductases Acting on CH-NH Group Donors