Abstract
The synthesis of C14-isocarboxazid (Marplan) labeled in the benzyl moiety has been described.
A 1 mg/kg intraperitoneal dose of C14-isocarboxazid has been found to be rapidly absorbed and distributed in the rat with the radioactivity reaching maximum tissue levels in 7.5 minutes. The fall-off of tissue radioactivity was characterized by a multi-component decline with the fast component exhibiting a half-life of approximately 30 minutes. The urinary radioactivity, which was virtually all accounted for as labeled hippurate, amounted to 75% of the dose in 24 hours. Secretion of radioactivity into the intestinal tract was also observed, with 7% of the dose found in the feces at the end of 24 hours.
At a dose of 40 mg/kg of C14-isocarboxazid, 42.5% of the dose was excreted in the urine in 24 hours, and approximately 64% of this urinary radioactivity was present in hippurate. Fecal excretion of radioactivity amounted to 22% of the dose.
The total excretion of radioactivity following equimolar doses of labeled isocarboxazid and iproniazid was found to be quantitatively similar after 1 day. However, analysis of the 6-hour excretion of radioactivity revealed that 45% of the iproniazid had been metabolized to pulmonary CO2 while 30% of the isocarboxazid was converted to urinary hippurate.
The significance of these results in relation to monoamine oxidase inhibition and the detailed elucidation of the biological fate of isocarboxazid is discussed.
Footnotes
- Received February 2, 1960.
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