Effect of pindolol on hormone secretion and body temperature: Partial agonist effects

Summary

Pindolol has been shown to be a partial agonist at 5-HT_1a receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT_1a partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT_1a receptors in man. To determine if pindolol has 5-HT_1a agonist as well as antagonist effects in man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order to 23 normal men with indwelling venous catheters and its effects on hormone secretion and body temperature noted. Pindolol significantly increased basal plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL) concentrations and body temperature. The increase in plasma cortisol due to pindolol suggests a 5-HT_1a agonist action and is consistent with a 5-HT_1a partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT_1a receptors. The effects of pindolol on plasma cortisol concentration and body temperature were significantly negatively correlated. Furthermore, these results indicate significant differences in the 5-HT_1a -dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and body temperature, and suggest that human basal PRL secretion is tonically stimulated by a 5-HT_1a mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT_1a receptor sensitivity between males and females, the results reported here need to be replicated in females. These differences in the effect of pindolol are discussed in terms of receptor reserve theory.