The effects of amiflamine, a reversible MAO-A inhibitor, on the first pass metabolism of tyramine in dog intestine.
The effects of amiflamine on tyramine deamination were studied using isolated loops of intestine in anesthetized dogs. In the pretreatment experiment, dogs were dosed with amiflamine (3.5 mg/kg/day) once daily for 3 days, with the study being carried out 3 hr after the final dose. [14C] Tyramine (50 mg and 50 microCi) in 10 ml of normal saline was introduced into the isolated loops of gut, and tyramine and p-hydroxyphenylacetic acid in the venous blood were separated by HPLC and measured by scintillation spectrometry. In the untreated dogs, approximately 15% of the tyramine passed through the gut wall unchanged. When tyramine and amiflamine (0.06 to 3.5 mg/kg) were administered simultaneously to the gut loop, about 27 to 65% of the tyramine passed through the gut wall unchanged. On the contrary, after pretreatment with amiflamine for 3 days, percentage of tyramine passing through the gut wall was not increased in comparison with the control. These results suggest that pretreatment with amiflamine does not produce drug concentrations in the lining cells of the gut sufficient to effectively inhibit the deamination of oral tyramine, which is administered at least 3 hr after the final dose of amiflamine.
D000818:Animals; D003641:Deamination; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D014439:Tyramine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D007527:Isoenzymes; D010627:Phenethylamines; D008995:Monoamine Oxidase; C031466:amiflamine; D014439:Tyramine