Is there a correlation between the concentration of beta-carbolines and their pharmacodynamic effects?

Abstract

Two sensitive and specific methods are presented for the determination of 6-OH-tetrahydronorharmane (6-OH-THN, 6-OH-THBC) and harmane (1-Me-BC). The concentration of 6-OH-THN in blood platelets from men was found 5.19 +/- 0.57 ng (mean +/- SEM) per 10(9) platelets, of acute schizophrenic patients 2.66 +/- 0.38 ng per 10(9) platelets, p less than 0.02, and in rats 6 - 13 ng x 10(9) platelets. The concentration of harmane in the urine of rats was measured 9.72 +/- 1.56 ng per 16 h. A load with ethanol caused an increased excretion of the beta-carboline in some rats. In pharmacological experiments substantial evidence was detected for a correlation between the (3H)-flunitrazepam displacing potency and the conflict-augmenting effects of beta-carbolines. Furthermore, a good correlation was found between the results of binding experiments and the antagonism of the beta-carbolines with respect to the activating effect of low doses of diazepam. No such correlation exists for the sedative effect.