Date of Award

1961

Degree Type

Thesis

Degree Name

Master of Science in Pharmacology

Department

Pharmacology

First Advisor

P. V. Buday

Abstract

Although a few disparate reports have been published to the contrary, accumulating evidence seems to indicate that the feeding of thyroid extract, or the parenteral administration of thyroxine, produce a decline in the monoamine oxidase activity in the livers of various animals. As a consequence this anti-enzymatic effect, and the resultant biologic sparing of catecholamines, has been incriminated as partly responsible for the hypersensitivity of hyperthyroid animals and isolated tissues, to the pharmacologic actions of sympathomimetic amines. Rather recently a class of anti-melancholic drugs, or “psychic energizers”, have been made clinically available. These agents seem to act as anti-depressants by virtue of their monoamine oxidase antagonizing properties. It was strange, therefore, to not in the literature that a clinical psychotherapeutic incompatibility existed between concurrent thyroid and monoamine oxidase inhibitor medication. Peculiar changes in thyroid function, blood pressure, and blood glucose levels were also noted clinically with the latter medicaments. The resent research was undertaken, using blood glucose, blood pressure, and acute and subacute toxicity studies as parameters, to evaluate these paradoxical reports. Male, albino rats were employed as subjects. Two chemically dissimilar, irreversible acting, monoamine oxidase inhibitors, iproniazid (Marsilid) and MO-911 (10 and 25 mg/kg) for a three week period elicited only inconsequential blood sugar changes in both euthyroid and hyperthyroid animals. Sytolic pressures became significantly elevated upon continued injection of either drug, and the pressor effects were enhanced by feeding a 2% thyroid diet. Limited dopamine excretion studies in hyperthyroid rats revealed no particular changes, whereas massive daily doses of iproniazid produced increased excretion of the catecholamine approximately 200 to 300 % after fifteen days of enzyme inhibitor treatment. These urinary results did not parallel the hypertensive effects. Weight loss, sluggishness, and gross and microscopic evidence of vital organ damage occurred with massive, daily doses of iproniazid. The acute lethal effects of M0-911 were augmented by thyroid feeding. These results seem to suggest strongly that the direct and indirect pharmacologic actions of iproniazid and M0-911, given in high daily doses to rats, are aggravated by a hyperthyroid state; these experimental findings have obvious clinical significance.

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