Production of Lactation by Non-Sedative Phenothiazine Derivatives

Development of the mammary glands and initiation of lactation in estradiolprimed rats were achieved by treatment with different tranquilizers. Perphenazine (Trilafon) was found to be the most active drug. SAR studies of the phenothiazines used showed that C1, CF₃ and SCH₃ substitution at position C₂ and a piperazine ring in the side-chain at position N₁₀ of the phenothiazine molecule are essential for eliciting strongmammotropic activity. A methoxy group at C₂ or a branched side-chain at Nlo destroy the mammotropic effect. No parallel exists between the tranquilizing and mammotropic effects of the derivatives. Thus, the two effects derive from different parts of the phenothiazine molecule, suggesting that the mammotropic effect of perphenazine is not due to its tranquilizing properties. This became evident when a mammotropic effect was obtained with perphenazine sulfoxide and chlorpromazine sulfoxide, both substances which lack any tranquilizing effect.