Correlations between different measures of antiserotonin activity of drugs. Study with neuroleptics and serotonin...

The antiserotonin properties of a series of neuroleptics, 5-HT-receptor blockers and some adrenoceptor antagonists were investigated in several in vivo test systems (L-5-HTP syndrome and 5-HT-paw edema in the rat) and in an in vitro test (isolated rat uterus preparation). The results were compared to the results obtained with these drugs in an in vivo 3H-spiperone binding assay in the rat. The computations of the relative ED50 (or IC50) values obtained in different test procedures showed that the ability of drugs to bind to 5-HT receptors labelled by 3H-spiperone in the rat frontal cortex correlates fairly well with their potencies to inhibit the L-5-HTP syndrome or 5-HT-induced rat pawedema (Spearman rank correlation coefficient, r = 0.80 and 0.79 respectively, n = 22). In an in vitro test (rat uterus) the estimated 5-HT-receptor blocking potency of the tested drugs did not, however, correlate with any of the in vivo measures used for this purpose. The results suggest, therefore, that for the determination of central antiserotonin effects of drugs in the rat, functional in vivo tests (L-5-HTP syndrome or 5-HT-induced rat paw-edema) could yield about the same information as the specific, in vivo 3H-spiperone binding assay. The 5-HT-receptor type mediating the behavioral responses to L-5-HTP is tentatively defined as a 5-HT2 receptor.