Is there a correlation between the concentration of beta-carbolines and their pharmacodynamic effects?
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.
D000470:Alkaloids / Q000097:blood*; D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000032:analysis*; D002243:Carbolines / Q000097:blood* / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D006247:Harmine / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology / Q000652:urine; D006801:Humans; D007211:Indoles / Q000097:blood*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism; D011963:Receptors, GABA-A; D012559:Schizophrenia / Q000097:blood*; D013050:Spectrometry, Fluorescence
D000470:Alkaloids; D002243:Carbolines; D007211:Indoles; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C009762:5-hydroxytryptoline; D006247:Harmine; C005010:harman; D003975:Diazepam