Effects of debrisoquin on the excretion of catecholamine and octopamine metabolites in the rat and guinea pig.
The effects of debrisoquin, administered daily for 4 days to rats (40 mg/kg, i.p.) and guinea pigs (4 mg/kg, i.p.), were determined for urinary excretion of several acidic and neutral amine metabolites, including the norepinephrine metabolites, 3-methoxy-4-hydroxyphenethylene glycol (MHPG) and vanillylmandelic acid (VMA), the dopamine metabolites, 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), and homovanillic acid (HVA), and the octopamine metabolite, p-hydroxyphenylglycol (pHPG). The excretion of MHPG was reduced to 32% of control in rats and to 46% in guinea pigs, HVA was reduced to 64 and 80% in these two species, respectively, and MHPE was lowered to 59% of control in the rat but was not affected in the guinea pig. DHPE and pHPG were not altered significantly in either species. VMA was a minor metabolite in both species, being less than 6% of MHPG, and its formation was blocked only partially (rat) or not at all (guinea pig) by debrisoquin. The data refute the idea based on previous in vitro studies that VMA is a major metabolite of norepinephrine in the periphery of the guinea pig as it is in man.
D015098:3-Methoxy-4-hydroxyphenylethanol / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003647:Debrisoquin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014642:Vanilmandelic Acid / Q000378:metabolism
D000588:Amines; D002395:Catecholamines; D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D015098:3-Methoxy-4-hydroxyphenylethanol; D008734:Methoxyhydroxyphenylglycol; D014642:Vanilmandelic Acid; D003647:Debrisoquin