5-hydroxytryptophol in human cerebrospinal fluid: conjugation, concentration gradient, relationship to 5-hydroxyindoleacetic acid, and influence of hereditary factors.

The serotonin metabolite 5-hydroxytryptophol was studied in human cerebrospinal fluid. A minor fraction (approximately 13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing beta-glucuronidase activity. A concentration gradient of 5-hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5-Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml +/- 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5-hydroxytryptophol.

5-hydroxytryptophol in the cerebrospinal fluid and urine of alcoholics and healthy subjects.

The serotonin metabolite 5-hydroxytryptophol was determined in cerebrospinal fluid and urine of alcoholics and healthy subjects, by a glass capillary gas chromatographic-mass spectrometric method. The urinary excretion rate (14.6 +/- 2.9 pmoles/mumoles creatinine) and urine (109 +/- 20 pmoles/ml) and cerebrospinal fluid (4.12 +/- 0.21 pmoles/ml) concentrations in healthy subjects were established. Only 1% of the 5-hydroxytryptophol in urine occurred in free form. Ethanol ingestion (80, 120 g) by healthy subjects lead to a 20--100-fold increase in the urinary excretion rate of 5-hydroxytryptophol. In cerebrospinal fluid the increase was about 60%. Alcoholics had increased urinary excretion rates and cerebrospinal fluid levels during intoxication, which were in the same range as in intoxicated healthy subjects. During recovery from intoxication, the 5-hydroxytryptophol level in alcoholics decreased, but the CSF levels were still higher than in healthy subjects.

Concentration of serotonin metabolites in the cerebrospinal fluid from alcoholics before and during disulfiram therapy.

The levels of 5-hydroxytryptophol and 5-hydroxyindoleacetic acid were measured in the cerebrospinal fluid before and after one week of disulfiram treatment (400 mg/day) from ten male hospitalized alcoholic patients. The disulfiram treatment induced elevated (P less than 0.001) levels of 5-hydroxytryptophol. The levels were higher than in a control group, both before (P less than 0.01) and after (P less than 0.001) the treatment. No effects on the levels of 5-hydroxyindoleacetic acid were noted. The results indicate an altered serotonin metabolism in alcoholics, which is further potentiated by disulfiram treatment.

Levels of 5-hydroxytryptophol in cerebrospinal fluid from alcoholics determined by gas chromatography-mass spectrometry.

A quantitative gas chromatographic-mass spectometric method using a deuterated analogue as internal standard was developed for the analysis of 5-hydroxytryptophol in cerebrospinal fluid. The analytical procedure involves the addition of the internal standard and 5-hydroxyindole to the cerebrospinal fluid followed by extraction into chloroform and derivatization with pentafluoropropionic anhydride. 5-Hydroxytryptophol levels in the CSF of male alcoholics and a control group were examined. During ethanol intoxication the mean level, 10.4 +/- 4.4 pmoles/ml, was significantly (P < 0.001) higher than in the controls, 3.31 +/- 0.94 pmoles/ml. The following morning the mean had decreased (P < 0.01) to 4.46 +/- 1.81 pmoles/ml. The level after 8 days was 4.70 +/- 2.47 pmoles/ml, which is lower than during intoxication (P <0.01). The levels found during the recovery from ethanol intoxication was not statistically different from the levels in the control group. These results indicate that serotonin metabolism in the central nervous system is affected by ethanol consumption.

5-Hydroxytryptophol in human cerebrospinal fluid: quantitative determination by gas chromatography-mass spectrometry using a deuterated internal standard.

Procedures for the quantification of 5-hydroxyindole-3-ethanol, or 5-hydroxy-tryptophol (5-HTOL), in human cerebrospinal fluid are described. 5-HTOL was determined as its di-pentafluorpropionyl derivative. Deuterium labelled 5-hydroxyindole-3-ethanol-a,a,b,b-d4 (5-HTOL-d4) was used as internal standard. Mass fragmentography was performed by double ion monitoring each for 5-HTOL and 5-HTOL-d4 and their ratios were determined for specificity. Assay sensitivities of 0.15 ng/ml were achieved using 2.0 ml of cerebrospinal fluid. Free 5-HTOL concentrations in human cerebrospinal fluid were determined to be 0.73 +/- 0.44 ng/ml (mean +/- S.D.) (range 0.33-2.11 ng/ml) from 15 patients with various neurological disorders, and 0.85 +/- 0.30 ng/ml (range 0.48-1.32 ng/ml) from 9 subjects who complained of low back pain but did not show signs of neurological illnesses.

Mass fragmentography of 5-hydroxytryptophol and 5-methoxytryptophol in human cerebrospinal fluid.

A specific and very sensitive method for the determination of 5-hydroxy-tryptophol (5-HTOL) and 5-methoxytryptophol (5-MTOL) in extracts from human cerebrospinal fluid (CSF) involving the use of mass fragmentography and pentafluoropriopionyl derivatives is described. 5-HTOL and 5-MTOL were determined in human CSF of three patients with leukaemia and from nine patients with neurological disorders. The concentration of free 5-HOT in CSF was in the range of 0.1-33 ng/ml and that of 5-MTOL was 0.3-13.9 ng/ml. For the first time the presence of these compounds in human material has been shown. The concentration of these two alcohols in CSF is markedly lower than the concentration of 5-hydroxyindoleacetic acid. These results suggest that human cerebral 5-hydroxytryptamine is preferentially metabolized to 5-HTOL-hydroxyindoleacetic acid rather than to 5-HTOL and 5-MTOL.