Effect of a Reserpine Analogue, Methyl-18-epi-o-methylreserpate Hydrochloride, on Lactogen Release from Rat Anterior Pituitary1

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Abstract
Evidence is presented which indicates that methyl-18-epi-o-methyl-reserpate hydrochloride (SU-9064), a reserpine analogue lacking hypotensive action, is capable of releasing lactogen from the anterior pituitary in a manner similar to that observed for reserpine. Studies conducted on the estrous cycle of the rat showed that upon administration of 2 mg/kg body weight of SU-9064 there resulted a prolongation of the cycle from 4.8 days for control animals to 11.6 days for injected animals. In a subsequent experiment, this response was attributed to the ability of SU-9064 to stimulate progesterone production from the corpus luteum of the cyclic rat, as indicated by positive deciduomata response. This latter response has been attributed only to either endogenous or exogenous lactogen. Observations on mammary glands indicated that SU-9064 stimulated gland growth and initiated secretory activity. Litter weight gains for animals administered the drug during lactation were significantly lower than the values obtained for control animals (107.3 vs. 118 g, respectively). Direct examination of the lactogen-releasing action of SU-9064 on lactating mothers, isolated from their litters and given either 2 or 5 mg/kg body weight, showed an 11.4 and 24.2% decrease, respectively, in anterior pituitary lactogen. The 24.2% decrease, when compared with control values, was highly significant. It is suggested that the lactogen-releasing ability of reserpine and its analogue resides in that part of the molecule common to both compounds.

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