Postnatal growth retardation in rats produced by the phenothiazine perphenazine

Perphenazine (PER), a potent phenothiazine, was administered to rats in a dose of 5 mg/kg, IP, daily for 19 days (experiment I) and 26 days (experiment II). In the first experiment, weights 3 days after treatment ended were PER 308 +/- 16 gm and saline controls 329 +/- 25 gm (P less than 0.01). Lengths were also smaller (221 +/- 2.2 mm vs 230 +/- 1.0 mm, P less than 0.05), and the slope of the growth curves for weight and length differed significantly as well. In a second experiment, the liquid diet pair-feeding technique was employed and demonstrated that the growth retardation due to PER could not be accounted for by a decrease in food intake. Pair-fed saline-treated rats who ate 2% less than PER-treated rats had a weight of 264 +/- 6 gm at the end of treatment compared to 236 +/- 9 gm for PER treated (P less than 0.01). It is concluded that PER treatment produces growth retardation and that this is not due simply to decreased food intake. The inhibition of growth hormone secretion produced by PER may be the mechanism of its growth-retarding effect. Since phenothiazines are administered chronically to children with mental disorders it would be important to determine if they produce a growth-retarding effect in humans.