Is pindolol a mixed agonist-antagonist at central serotonin (5-HT) receptors?

The effects of the non-selective beta-adrenergic blocking agent pindolol upon central monoaminergic neurotransmission in rats were studied by means of in vivo biochemical methods. It was found that (-)-pindolol elicited a clearcut, selective, dose-dependent and stereospecific reduction of brain 5-HT synthesis rate. The synthesis reduction was not accompanied by any change in the tissue tryptophan levels and could not be prevented by depleting the monoamine stores by means of reserpine. Furthermore, in non-pretreated animals, (-)- but not (+)-pindolol (nor the beta 1- and beta 2-selective adrenoceptor antagonists metoprolol, betaxolol and ICI 118,551) decreased the 5-HIAA level and the 5-HIAA/5-HT ratio while neither enantiomer altered the concentrations of 5-HT or NA, or DA and its metabolites. It is suggested that these effects of (-)-pindolol may be due to direct stimulation of 5-HT receptors in the CNS. The action of the compound is discussed within the context of literature data indicating its ability to act as an antagonist of certain other aspects of 5-HT receptor activation. The possibility is considered that, in addition to its beta-adrenergic properties, (-)-pindolol is a mixed agonist-antagonist at central 5-HT receptors.