The monoamine oxidase inhibitor mebanazine (Actomol) was found to reduce the growth of cartilage, and the normal increase in body weight and pituitary weight in growing male rats. The inhibitory effect of mebanazine on cartilage growth is only partially overcome by concomitant injection of growth hormone. The inhibitory effect on growth is much greater when mebanazine is injected together with hydrocortisone; it exceeds by far the sum of the effects of mebanazine or hydrocortisone alone (augmentative synergism).
Mebanazine also inhibits cartilage growth in normal rats receiving metyrapone (Metopirone—which inhibits corticosteroid production) and in adrenalectomized animals receiving hydrocortisone. Mebanazine stimulates involution of the thymus and depletion of ascorbic acid from the adrenal glands of rats. This shows that mebanazine releases adrenocorticotrophic hormone in normal rats and in rats receiving high doses of hydrocortisone.
Our results thus suggest that the inhibitory effect of mebanazine on growth is twofold: it potentiates a corticosteroid which itself is a growth inhibitor and in addition blocks the release of growth hormone from the pituitary by a specific mechanism inherent in the action of mebanazine as an enzyme blocker.
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