Leiomyomas developed in the ovarian suspensory ligament (costo-uterine muscle) of rats after long-term treatment with several beta2-adrenoceptor stimulant drugs. The response was evidently related to excessive adrenergic stimulation of a tissue with a high density of β2-receptors; was inhibited by β blockade; and was directly related to in vitro pharmacologic potency. Tumor development was dependent on continuous administration of adequate dosages to a susceptible strain of rat. Histologically, all tumors were benign and none were malignant. After many years of clinical experience, there are no known reports of this response in human patients receiving β2-adrenoceptor-stimulant drugs.
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