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PubMed1999

Comparison of urinary 5-hydroxytryptophol, breath ethanol, and self-report for detection of recent alcohol use during outpatient treatment: a study on methadone patients.

This study compared urinary 5-hydroxytryptophol (5HTOL) with breath-ethanol testing as objective ways to disclose recent drinking by outpatients attending a methadone maintenance treatment clinic. Information about quantity and frequency of alcohol use was obtained by confidential self-reports. Random screening was performed on Mondays-Fridays in connection with routine clinic visits for methadone dosing. An observed urine sample for monitoring of illicit drug use and determination of 5HTOL, expressed as a ratio to 5-hydroxyindole-3-acetic acid (5HIAA), was obtained from 202 patients (59 women and 143 men), 16 of whom refused to complete the self-report and/or do a breath-ethanol test. Patients taking disulfiram or calcium carbimide for alcohol detoxification were excluded. Among the 177 subjects remaining, 47 (26.6%) reported intake of any alcohol on the previous day (range, 10-230 g ethanol; median, 40). Only four of those could be identified by a positive breath-test, while 17 showed a urinary 5HTOL/5HIAA ratio above the cutoff limit. Their alcohol consumption (median, 60 g) was significantly higher compared with those showing ratios within the reference interval (median, 35 g). The sensitivity of 5HTOL/5HIAA testing for detecting self-reported drinking in excess of 50 g ethanol was 77%. An additional nine patients who claimed abstinence still showed abnormal 5HTOL/5HIAA ratios, and so did three of the patients who refused to do a breath-ethanol test and/or complete the self-report. Altogether, 59 of 190 methadone-maintained patients (31.1%) had been drinking any alcohol on the previous day (i.e. Sunday-Thursday) according to self-report and/or urinalysis data, 29 (49.2%) of whom were identified by the urinary 5HTOL/5HIAA ratio and only four (6.8%) by utilizing breathalyzer.

Alcohol Drinking↗
PubMed1983

The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol in the pineal gland of the male Wistar rat.

The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol has been investigated using different experimental procedures. It was demonstrated that when GABA and an acetyl donor were added to the incubation medium together, a significant increase in synthesis of the N-acetylated products occurred during the night. Moreover there was a large increase in N-acetylserotonin synthesis at 15(00) hrs although none was observed in the control experiments. However, when GABA was added 20 min before the acetyl donor, synthesis of the N-acetylated products was significantly less. The opposite effect was observed for the O-acetylated indoles. These results confirm the proposal by Ebadi et al. (1982) that GABA, like norepinephrine, may be a regulator of melatonin synthesis. As melatonin is implicated in the regulation of reproduction it may be that GABA is equally significant in this regulatory effect.

Acetylation↗
PubMedDate not supplied

Urinary ethyl glucuronide and 5-hydroxytryptophol levels during repeated ethanol ingestion in healthy human subjects.

AIMS: This study investigated the stability and reproducibility of urinary ethyl glucuronide (EtG) and the 5-hydroxytryptophol (5-HTOL) to 5-hydroxyindole-3-acetic acid (5-HIAA) ratio, both of which are used as biochemical markers of recent alcohol consumption, after single and multiple oral doses of ethanol in healthy human subjects. METHODS: Nine females aged 19-27 years drank ethanol (8%, w/v, in juice) or placebo (juice) in random order. The intervention consisted of 0.4 g/kg (22-28 g) of ethanol or placebo twice daily (in the morning and evening) during 8 consecutive days, starting in the evening on day 1. Spot urine samples of the first morning void were collected during the 8-day drinking period and for another 3 days (days 9-11) with no intake of ethanol or placebo. Ethanol, EtG, 5-HTOL and 5-HIAA were determined in the urine samples by headspace GC, LC-MS, GC-MS and HPLC, respectively. RESULTS: The individual results during the drinking period were highly variable, both within and between subjects, ranging from 0-7.3 mmol/l for ethanol, 1.4-71.0 mg/l for EtG, 0.1-4.5 mg/mmol for the EtG/creatinine ratio, and 2-109 nmol/ micro mol for 5-HTOL/5-HIAA. The placebo group consistently showed negative values for ethanol (< 0.1 mmol/l) and 5-HTOL/5-HIAA (< 15 nmol/ micro mol), but two samples were positive for EtG (> 0.1 mg/l). In the morning of day 9 (i.e. approximately 14-15 h after the last dose), ethanol was no longer measurable in urine and the 5-HTOL/5-HIAA ratio had returned to below the reference value, but detectable levels of EtG (11.3 +/- 6.0 mg/l, mean +/- SD) and the EtG/creatinine ratio (1.0 +/- 0.3 mg/mmol) were found in all samples. CONCLUSIONS: The results confirm the increase in urinary EtG and 5-HTOL levels during acute ethanol intake, although the individual values were highly variable both within and between subjects. No significant accumulation of either compound occurred upon multiple-dose administration of 0.8 g/kg (44-57 g) ethanol per day for approximately 1 week.

Adult↗
PubMed2005

Comparison of serum fatty acid ethyl esters and urinary 5-hydroxytryptophol as biochemical markers of recent ethanol consumption.

AIMS: To examine the effects of an acute dose of ethanol on serum fatty acid ethyl esters (FAEEs) concentration and urinary 5-hydroxytryptophol (5-HTOL)/5-hydroxyindole-3-acetic acid (5-HIAA) ratio. METHODS: Sixteen (14 male, 2 female) heavy alcohol drinkers were tested in a single, 2-day long session. Six participants received 1.5 g/l of ethanol/l of body water (approximately 0.75 g/kg of body weight, low dose group: LD) and 10 participants received 2.0 g/l of ethanol ( approximately 1.0 g/kg of body weight, high dose group: HD) in four divided doses every 20 min. Blood, urine, and breath samples were collected repeatedly over 36 h following the ingestion of ethanol and were analyzed for the presence of FAEE, 5-HTOL/5-HIAA, and ethanol, respectively. Serum gamma-glutamyltransferase (GGT), a marker of chronic ethanol use, was also included. RESULTS: The breath ethanol level peaked approximately 1 h after the last dose, at 95 and 120 mg/dl for the LD and HD groups, respectively. The mean ratio of urinary 5-HTOL/5-HIAA was significantly elevated 5 and 9 h after ethanol administration, but returned to baseline 13 h after ethanol administration. This ratio was twice as high for the HD group compared with the LD group. Serum levels of FAEEs were significantly elevated at 5 h, but not 13 h after ethanol administration. There were no time-dependent changes in serum GGT levels. CONCLUSIONS: Measuring the levels of FAEE and 5-HTOL/5-HIAA ratio provides a convenient method to detect recent, particularly binge-type, ethanol use, but these measures may have limited applicability in detecting ethanol use in traditional clinical trial settings.

Adult↗
PubMedDate not supplied

Urinary excretion of methanol and 5-hydroxytryptophol as biochemical markers of recent drinking in the hangover state.

Twenty healthy social drinkers (9 women and 11 men) drank either 50 g of ethanol (mean intake 0.75 g/kg) or 80 g (mean 1.07 g/kg) according to choice as white wine or export beer in the evening over 2 h with a meal. After the end of drinking, at bedtime, in the following morning after waking-up, and on two further occasions during the morning and early afternoon, breath-alcohol tests were performed and samples of urine were collected for analysis of ethanol and methanol and the 5-hydroxytryptophol (5-HTOL) to 5-hydroxyindol-3-ylacetic acid (5-HIAA) ratio. The participants were also asked to quantify the intensity of hangover symptoms (headache, nausea, anxiety, drowsiness, fatigue, muscle aches, vertigo) on a scale from 0 (no symptoms) to 5 (severe symptoms). The first morning urine void collected 6-11 h after bedtime as a rule contained measurable amounts of ethanol, being 0.09 +/- 0.03 g/l (mean +/- SD) after 50 g and 0.38 +/- 0.1 g/l after 80 g ethanol. The corresponding breath-alcohol concentrations were zero, except for three individuals who registered 0.01-0.09g/l. Ethanol was not measurable in urine samples collected later in the morning and early afternoon. The peak urinary methanol occurred in the first morning void, when the mean concentration after 80 g ethanol was approximately 6-fold higher than pre-drinking values. This compares with a approximately 50-fold increase for the 5-HTOL/5-HIAA ratio in the first morning void. Both methanol and the 5-HTOL/5-HIAA ratio remained elevated above pre-drinking baseline values in the second and sometimes even the third morning voids. Most subjects experienced only mild hangover symptoms after drinking 50 g ethanol (mean score 2.4 +/- 2.6), but the scores were significantly higher after drinking 80 g (7.8 +/- 7.1). The most common symptoms were headache, drowsiness, and fatigue. A highly significant correlation (r = 0.62-0.75, P <0.01) was found between the presence of headache, nausea, and vertigo and the urinary methanol concentration in the first and second morning voids, whereas 5-HTOL/5-HIAA correlated with headache and nausea. These results show that analysing urinary methanol and 5-HTOL furnishes a way to disclose recent drinking after alcohol has no longer been measurable by conventional breath-alcohol tests for at least 5-10h. The results also support the notion that methanol may be an important factor in the aetiology of hangover.

Adult↗
PubMed2005

Detection of recent ethanol intake with new markers: comparison of fatty acid ethyl esters in serum and of ethyl glucuronide and the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid in urine.

BACKGROUND: At present, recent ethanol consumption can be routinely detected with certainty only by direct measurement of ethanol concentration in blood or urine. Because ethanol is rapidly eliminated from the circulation, however, the time span for this detection is in the range of hours. Several new markers have been proposed to extend the detection interval, but their characteristics have not yet justified their use in routine clinical practice. We therefore investigated three new markers and compared their kinetics and sensitivities: (1) fatty acid ethyl esters (FAEEs) in serum, (2) ethyl glucuronide (EtG) in urine, and (3) the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid (5-HTOL/5-HIAA) in urine. METHODS: Seventeen healthy men participated in a drinking experiment. Blood and urine samples were collected twice daily on three consecutive days and once daily on days 4 and 5. Ethanol concentration was determined by gas chromatography, FAEE levels, by gas chromatography with mass spectrometry, EtG concentration, by liquid chromatography-tandem mass spectrometry, and 5-HTOL/5-HIAA ratio, by high-performance liquid chromatography. RESULTS: The peak serum ethanol concentrations of the subjects ranged from 5.4 to 44.7 mmol/liter (mean +/- SD, 30.1 +/- 9.1 mmol/liter). In the case of the serum ethanol determination, 100% sensitivity was reached only immediately after the end of the drinking experiment, and in the case of FAEE levels and 5-HTOL/5-HIAA ratio, it tested for 6.7 hr after the end of the ethanol intake. Thereafter, these latter parameters declined until 15.3 hr (FAEEs) and 29.4 hr (5-HTOL/5-HIAA), subsequently remaining in a stable range until 78.5 hr without further decrease. In contrast, EtG concentration showed 100% sensitivity until 39.3 hr and thereafter decreased, falling to below the limit of quantification of 0.1 mg/liter at 102.5 hr. CONCLUSION: After moderate drinking, EtG in the urine proved to be a superior marker of recent ethanol consumption in healthy subjects. This is because EtG is a direct ethanol metabolite, it occurs in the urine only when ethanol has been consumed, and its sensitivity remains at the level of 100% for 39.3 hr.

Adult↗
PubMed1980

Effects of 5-hydroxytryptophol, a 5-hydroxytryptamine metabolite, on isolated cerebral arteries of the dog.

5-Hydroxytryptophol (5-HTOL) caused a dose-dependent contraction of helically-cut strips of dog cerebral arteries. The 5-HTOL-induced contraction was suppressed by cinanserin, as was the contraction induced by 5-hydroxytryptamine (5-HT). Treatment with 5-HTOL shifted the dose-response curve for 5-HT to the right and downward in a dose-dependent manner, but did not attenuate the contractile response to prostaglandin F2a. It may be concluded that 5-HTOL elicits cerebroarterial contractions by activating tryptaminergic receptors and also interferes with the action of 5-HT on the receptors.

Animals↗
PubMed1992

Urinary 5-hydroxytryptophol: a possible marker of recent alcohol consumption.

Urinary 5-hydroxytryptophol (5-HTOL) is currently being evaluated as a marker of recent alcohol consumption. To compensate for urinary dilution, the molar ratio between 5-HTOL and 5-hydroxyindole-3-acetic acid (5-HIAA) is used. The 5-HTOL/5-HIAA ratio showed a satisfactory degree of individual stability when it was followed in a group of teetotallers for 1 month. The mean value of 5-HTOL/5-HIAA in a group of 69 persons abstaining from alcohol was 7.6 (pmoles 5-HTOL/nmoles 5-HIAA). Ninety-seven percent had values ranging from 4 to 17, with no value exceeding 20. A group of healthy volunteers were tested 12 hr after alcohol consumption and showed a dose-dependent and statistically significant elevation in the 5-HTOL/5-HIAA ratio. Four regular alcohol consumers who were followed during a period of 3 months of drinking had elevated values of the 5-HTOL/5-HIAA ratio in 60% of their urine samples. The present study indicates that urinary 5-HTOL/5-HIAA is a sensitive and reliable marker of recent alcohol consumption. We propose that a 5-HTOL/5-HIAA ratio greater than 20 (pmoles/nmoles) can be used to indicate recent alcohol consumption. This limit gives a low frequency of false positives; the statistical probability of having a value greater than 20 during abstinence from alcohol was calculated to be less than 0.001.

Adult↗
PubMed1993

Detection of relapses in alcohol-dependent patients: comparison of carbohydrate-deficient transferrin in serum, 5-hydroxytryptophol in urine, and self-reports.

In this study, detection of relapses in male alcohol-dependent patients by biochemical markers and self-reports of alcohol consumption were examined. The patients were trying to stay abstinent from alcohol for 6 months. Four of 15 patients dropped out from treatment after 50-110 days. Ratios of urinary 5-hydroxytryptophol (5-HTOL)/5-hydroxyindole-3-acetic acid and 5-HTOL/creatinine were measured daily and serum carbohydrate-deficient transferrin (CDT) once a week. Clinical ratings and self-reports about alcohol consumption were performed three times a week. According to the self-reports, 3 of the patients drank alcohol frequently, 5 of them sporadically, and 7 of the patients reported no alcohol intake at all. According to the 5-HTOL marker, 4 of the patients drank alcohol frequently, and 11 of them sporadically. No one had all urinary levels of 5-HTOL marker below the reference level. According to the CDT, 3 of the patients drank alcohol frequently, 3 sporadically, and in 9 of the patients no elevated levels of CDT were found. Elevated levels of CDT were preceded by increased values of 5-HTOL marker. The combined results suggested that no one of the patients was totally abstinent from alcohol during the treatment period. The 5-HTOL marker seemed to be useful to reveal recent alcohol drinking, and CDT proved to be useful to validate the patients' self-reports. Together the two biochemical markers showed complementary properties in early detection of relapse and treatment monitoring.

Adult↗
PubMed1987

Investigation of circadian rhythms for pineal 5-hydroxytryptophol and other indoles in the rat.

5-hydroxytryptophol (5HTL) occurs in the pineal gland of the rat at levels comparable to those of melatonin, yet few studies have been conducted to investigate 5HTL as a potential alternative pineal hormone. In this study the pineals of 90-day-old male Sprague Dawley rats have been assayed by high performance liquid chromatography coupled with electrochemical detection. Significant (P less than .0001) circadian variation was measured in 5HTL levels, and a fivefold plateau elevation occurred during the middle of the light period. By comparison with the timing of the variations in N-acetyl serotonin and melatonin levels, it is suggested that 5HTL may not be regulated by simple competition with N-acetyl transferase for the common substrate 5HT but may, in fact, be regulated independently. Literature supporting such a suggestion, and a model incorporating it, are presented for discussion.

Animals↗
PubMed1982

Factors influencing melatonin, 5-hydroxytryptophol, 5-hydroxyindoleacetic acid, 5-hydroxytryptamine and tryptophan in rat pineal glands.

Using a simple high performance liquid chromatographic method, we measured melatonin, N-acetyl-5-hydroxytryptamine (NAc-5HT), 5-hydroxytryptophol (5HTOL), 5-hydroxyindoleacetic acid (5HIAA), 5-hydroxytryptamine (5HT) and tryptophan in single rat pineal glands. 5-Methoxytryptophol and 5-methoxyindoleacetic acid were not detected at levels which have been reported previously. 5HTOL, 5HIAA and 5HT showed the opposite diurnal rhythm to NAc-5HT and melatonin. Light during the dark period lowered melatonin while increasing 5HTOL, 5HIAA and 5HT. As the peak 5HTOL levels were higher than the peak melatonin levels, the functional significance of 5HTOL deserves consideration. Tryptophan administration increased melatonin and 5HTOL as well as the other indoles.

Animals↗
PubMed1992

Occurrence in vivo of 5-hydroxytryptophol in the brain of rats treated with ethanol.

The effect of ethanol (EtOH) on the release of dopamine (DA) and 5-hydroxytryptamine (5-HT) and the efflux of their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindol-3-ylacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL) from the striatum of the freely moving rat were studied in vivo using brain microdialysis. Striatal DA and 5-HT release was maximally enhanced at first fraction after the administration of EtOH (2 g/kg, i.p.). The level of the DA-oxidized metabolite, DOPAC, decreased significantly. In the 5-HT metabolic pathway, the oxidized metabolite, 5-HIAA, did not show significant changes, whereas levels of the biogenic alcohol 5-HTOL were increased to 180% at 90 min following EtOH administration. It is suggested that EtOH, most probably via acetaldehyde, could shift 5-HT metabolism from the oxidative to the reductive pathway in the rat brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Distinguishing ingested ethanol from microbial formation by analysis of urinary 5-hydroxytryptophol and 5-hydroxyindoleacetic acid.

During the metabolism of ethanol, the metabolic conversion of serotonin (5-hydroxytryptamine) is altered, and, as a consequence, the ratio of 5-hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) excreted in urine increases appreciably. The ratio of metabolites remains elevated for several hours after ethanol is no longer detectable. In the present study, urine specimens were supplemented with glucose and Candida albicans, a common human pathogenic yeast, and the formation of ethanol and the changes in the 5HTOL/5HIAA ratio were examined during one week of storage. Despite the production of high concentrations of ethanol (peak level 171 mmol/L, or 788 mg/dL), the 5HTOL/5HIAA ratio remained constant. The urinary 5HTOL/5HIAA ratio was also compared with urinary and blood ethanol levels in specimens selected at random during forensic autopsies. Elevated 5HTOL/5HIAA ratios were found in all specimens with detectable urinary ethanol. Some specimens showed elevated ratios of serotonin metabolites even though no ethanol was detected, indicating that these subjects had consumed ethanol prior to death but that the concentration had already returned to zero or was below the detection limit. In one case, postmortem ethanol formation was suspected, because blood ethanol concentration was 16.8 mmol/L (77 mg/dL) whereas urinary ethanol was zero. The urinary 5HTOL/5HIAA ratio fell within normal limits, which confirmed the suspicion of postmortem ethanol synthesis in the blood specimen. The present results indicate that the 5HTOL/5HIAA ratio in urine provides a useful method to distinguish between ethanol that might have been synthesized postmortem, or generated in vitro, from ethanol excreted in urine as a result of drinking.

Adult↗
PubMed1996

Laboratory testing for recent alcohol consumption: comparison of ethanol, methanol, and 5-hydroxytryptophol.

The ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid (5HTOL/5HIAA) in urine was compared with concentrations of ethanol and methanol as a way to monitor recent alcohol consumption. During detoxification of alcohol-dependent subjects, ethanol persisted longer in urine than in breath or plasma. Blood and urinary methanol remained increased for 2-6 h after blood ethanol had returned to background concentrations, whereas 5HTOL/5HIAA remained increased for 6-15 h. In healthy volunteers who had ingested alcohol (range 3-98 g) the previous afternoon or evening, 87% (for men) and 59% (for women) of all drinking occasions exceeding 7 g of alcohol were identified by an increased 5HTOL/5HIAA in the first morning urine void. This compared with 32% and 12%, respectively, identified by analysis of ethanol (>200 micromol/L). No gender difference in the excretion pattern of 5HTOL/5HIAA was seen. The results demonstrate that 5HTOL/5HIAA provides a specific and more sensitive method to detect recent alcohol consumption than does ethanol or methanol.

Adult↗
PubMed1994

The use of 5-hydroxytryptophol as an alcohol intake marker.

5-Hydroxytryptophol (5HTOL) occurs naturally in animals as a metabolite of serotonin. Ethanol interacts with serotonin metabolism to increase the production of 5HTOL at the expense of 5-hydroxyindoleacetic acid (5HIAA). This can be used clinically in the treatment of alcohol dependence to improve the detection of relapse in alcohol drinking, by monitoring daily the urinary 5HTOL/5HIAA ratio. In one experiment the sensitivity of this marker in detecting alcohol drinking the previous day was more than 10-fold greater than measuring urinary ethanol. Genetic polymorphism in alcohol and aldehyde dehydrogenases, which is known to influence the ethanol metabolism, does not confound the clinical use of 5HTOL as a marker. Disulfiram and cyanamide, however, will elevate urinary 5HTOL/5HIAA ratio.

Alcohol Drinking↗
PubMed1997

Urinary 5-hydroxytryptophol following acute ethanol consumption: clinical evaluation and potential aviation applications.

HYPOTHESIS: The unknown prevalence of alcohol use and misuse among aviation pilots, crewmembers and associated support personnel call for continuous improvement of methods for detecting recent alcohol use. Early detection is essential to proper treatment and prevention of potentially catastrophic mishaps. Urinary 5-hydroxytryptophol (5HTOL), a serotonin (5HT) metabolite, has shown promise in the clinical setting as a noninvasive marker of recent alcohol consumption. METHODS: The urinary 5HTOL concentrations of 11 male and female subjects were followed for approximately 24 h following dosing with ethanol 0.6 g.kg-1. Concentrations were reported as a ratio of 5HTOL to 5-hydroxy-indoleacetic acid (5HIAA), 5HTOL/5HIAA (pmol/nmol), to compensate for urinary dilution and elevated 5HTOL levels due to dietary intake. Data from one male subject was excluded after he admitted to continued alcohol consumption subsequent to dosing and missing several urine samples. RESULTS: 5HTOL/5HIAA ratios remained above the 15 pmol/nmol cutoff for recent alcohol use for approximately 11-16 h in all except one subject. Calculations based on body weight and administered alcohol dose suggest that measurable blood alcohol levels would exist for only 5-7 h post ingestion. CONCLUSION: This study confirmed the extended elevation of 5HTOL/5HIAA ratios observed in earlier studies, even at the relatively low alcohol dose used herein. 5HTOL appears to be a marker for acute alcohol consumption worthy of further investigation by military and civilian authorities. Potential aviation applications of 5HTOL include validation of measurable blood alcohol concentrations, investigation of poor performance due to hangover effects, and as a forensic toxicology tool in aircraft accident investigations to distinguish between actual alcohol ingestion and post-mortem alcohol synthesis.

Acute Disease↗
PubMed1998

Monitoring relapse drinking during disulfiram therapy by assay of urinary 5-hydroxytryptophol.

Screening for recent alcohol use by testing urine for the ratio of 5-hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) was performed in 10 methadone patients on disulfiram (Antabuse) maintenance therapy in an outpatient setting. Apart from alcohol ingestion, treatment with aldehyde dehydrogenase inhibitors such as disulfiram is the only known cause of an abnormally high 5HTOL/5HIAA ratio. After introduction of drug therapy, increased ratios were observed in all patients. The new higher level reached was relatively stable over time within the same patient but variable between patients. Four patients continued to consume alcohol, as evidenced by 5HTOL/5HIAA ratios well above the new individual plateau, while still taking 400 mg disulfiram 3 times per week under strict supervision. To try to achieve sobriety in two patients who drank frequently while on therapy, the disulfiram dose was doubled. Continued testing demonstrated this to increase the 5HTOL/5HIAA steady-state level further, and the absence of extreme values above this new baseline level indicated adherence to abstinence with possibly one single relapse. When disulfiram administration was discontinued, as planned, by five of the patients, four of them returned to drinking very soon. The present results show that during disulfiram maintenance the continuous inhibition of aldehyde dehydrogenase produces a new higher and dose-related 5HTOL to 5HIAA steady state level in urine, but relapse to drinking will still lead to further increased 5HTOL/5HIAA ratios. It is also suggested that an individual dose-titration regimen, whereby the disulfiram dose is raised gradually until 5HTOL/5HIAA testing indicates sobriety, will improve therapeutic effectiveness.

Adult↗
PubMed2005

One electron oxidation induced dimerization of 5-hydroxytryptophol: role of 5-hydroxy substitution.

Reaction of one-electron oxidant (Br(2)(*-)) with tryptophol (TP) and 5-hydroxytryptophol (HTP) have been studied in aqueous solution in the pH range from 3 to 10, employing nanosecond pulse radiolysis technique and the transients detected by kinetic spectrophotometry. One-electron oxidation of TP has produced an indolyl radical that absorbs in the 300-600 nm region with radical pK(a) = 4.9 +/- 0.2, while the reaction with HTP has produced an indoloxyl radical with lambda(max) at 420 nm and radical pK(a) < 3. Hydroxyl radicals ((*)OH) react with these two compounds producing (*)OH radical adducts that undergo water elimination to give one-electron-oxidized indolyl and indoloxyl radical species, respectively. The indoloxyl radicals react with the parent compound to form dimer radicals with an average association constant of (6.7 +/- 0.4) x 10(4) M(-1). No such dimerization is observed with indolyl radical, indicating that the presence of the 5-hydroxy group markedly alters its ability to form a dimer. A possible explanation behind such a difference in reactivity has been supported with ab initio quantum chemical calculations.

Journal Article↗