6-HYDROXY-TETRAHYDRONORHARMANE (6-HYDROXY-TETRAHYDRO-BETA-CARBOLINE), A NEW ACTIVE METABOLITE OF INDOLE-ALKYLAMINES IN MAN AND RAT

6-OH-Tetrahydronorharmane (6-OH-THN) is formed probably by condensation of the putative neurotransmitter 5-hydroxytryptamine (5-HT) and formaldehyde. After loading four male human volunteers orally with 300 mg l-5-hydroxytryptophan, the precursor of 5-HT, the glucuronic acid conjugate of 6-OH-THN was found in the urine. After hydrolysis the β-carboline was identified by mass-spectrometry. 6-OH-THN was extracted and then separated by high performance liquid chromatography and thin layer chromatography. In platelets of rats 52 ng per 1×108 platelets could be measured. In the forebrain of rats the concentration was found near the limits of detection. Thus, the present data strengthen the evidence that the condensation reaction is the first step of a new pathway for indolealkylamines. In behavioural experiments authentic 6-OH-THN was injected intracisternally into mice. This route of application was chosen since relatively minor amounts of 6-OH-THN cross the blood brain barrier. The substance caused hypothermia after application of 0.3 μg and more, a reduced nociception at a dose of 10 μg and more, diminished motility at 20 μg and more and exerted cataleptic effects at 10 μg and more in a dose-dependent manner. However, the dose-effectcurves for nociception and catalepsy were bell-shaped. Thus, at higher doses the behaviour of the animals did not differ from that found after injection with solvent only. The effects were compared in some experiments with those of THN and 6-methoxy-THN. 6-OH-THN is a biologically active substance. It may act as a modulator of neuronal mechanisms. © 1979 Springer-Verlag.