Summary: The present paper shows that tetrahydronorharmane (tetrahydro-0-carboline) exists in human platelets. The concentration of tetrahydronorharmane in platelets from 10 ml platelet rich plasma was in the range of 9.3 to 25.6 pmol (n=8). Ingestion of tryptamine hydrochloride (n=4) three times daily for three consecutive days and of 19.6 mmol Z)^-tryptophan (n=7) the evening (10 p. m.) before the blood collection did not lead to an increase of tetrahydronorharmane in platelets.
Nachweis von Tetrahydronorharman (Tetrahydro-ß-carbolin) in menschlichen Thrombocyten
The distribution, metabolism and elimination into the urine of (14C)-tetrahydronorharmane (THN) as well as of (14C)-6-hydroxy-tetrahydronorharmane (6-OH-THN) are investigated in female and male rats. Following intravenous injection of (14C)-THN radioactivity was detected in all organs examined, namely blood, brain, lung, adrenal gland, small intestine, fat tissue, kidney and liver. In the brain the elimination half life of THN was calculated to be 1.8 h, the elimination half life of the radioactivity in the blood 6.24 h, and the accumulation half life in the urine 9.24 h. The elimination of 6-OH-THN into the urine is faster than that of THN. At least four metabolites of (14C)-THN were found in the urine of female rats. Two different metabolic pathways are discussed, firstly, hydroxylation followed by conjugation with glucuronic and sulfuric acids and secondly, dehydrogenation, followed by oxygenation. In female rats only traces of the conjugated metabolites are hydrolysed by arylsulfatase, whereas in male rats approximately 2/5 are cleaved by this enzyme. Pretreatment of male rats with 3-methylcholanthrene induced conjugation, whereas phenobarbital had no obvious effect on the pattern of metabolites. SKF 525 A and CFT 1201 both prevented almost completely the formation of conjugates from THN.
Rats were injected intraperitoneally once every 12 h with 10 mg/kg delta-9-THC and the time course of the depressant effect was determined after one and nine injections. The motor activity of naive rats was maximally depressed between 1 and 4 h and returned to control levels 8 h after treatment. After nine injections, the maximum intensity of the depressant effect was not different from that after one injection but had completely disappeared at an earlier time point (4 h p.i.) indicating the development of tolerance to the duration of effect on motor activity. The subcellular distribution studies in brains of tolerant and non-tolerant rats indicated that an accelerated shift in the concentrations of delta-9-THC and 11-OH-delta-9-THC towards highly polar metabolites in the brains, rather than an increased elimination of these cannabinoids or decreased sensitivity of the brain may be responsible for the development of tolerance to delta-9-THC.
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