Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline.
The effect of the monoamine oxidase inhibitor selegiline on tyramine metabolism and intravenous and oral tyramine pressor sensitivity was studied in healthy subjects. After oral doses of tyramine, which caused systolic blood pressure to increase by 30 mm Hg, we determined plasma concentrations of p-hydroxyphenylacetic acid (HPAA) and of conjugated and unconjugated tyramine. When 20 mg/day of selegiline was administered, the AUCspec of HPAA decreased from 86% to 64% and the AUCspec of conjugated tyramine increased from 13% to 35% of the sum of total tyramine and HPAA. Pressor sensitivity was enhanced more with oral administration of tyramine than with intravenous administration of tyramine. After the drug was discontinued, initial values were reached within 4 days (one subject) and 2 weeks (two subjects). Fifty-five percent of the selegiline dose was eliminated in urine as amphetamine and methamphetamine. The findings support the assumption that selegiline does not selectively inhibit monoamine oxidase-B (MAO-B) when administered in doses of 20 mg/day and higher.
Schulz
R
R
Human Pharmacology Institute, Ciba-Geigy GmbH, Tübingen, West Germany.
Antonin
K H
KH
Hoffmann
E
E
Jedrychowski
M
M
Nilsson
E
E
Schick
C
C
Bieck
P R
PR
D000284:Administration, Oral; D000328:Adult; D000661:Amphetamine / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D002849:Chromatography, Gas; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008694:Methamphetamine / Q000652:urine; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D010648:Phenylacetates / Q000097:blood; D011897:Random Allocation; D012642:Selegiline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014439:Tyramine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D010648:Phenylacetates; D012642:Selegiline; C008070:4-hydroxyphenylacetic acid; D008694:Methamphetamine; D000661:Amphetamine; D014439:Tyramine