(+-)-5-Hydroxytryptophan

Solubilities: 2.5 g/100 mL in 50% boiling alcohol; 5.5 g/100 mL in water at 100 °C

In water, 1X10+4 mg/L at 5 °C

298-300 °C (decomposes)

MP: 273 °C (decomposes); specific optical rotation: +16.0 deg at 22 °C (c=1 in 4M HCl); -32 deg at 22 °C (c=1 in H2O) /(S)-5-Hydroxytryptophan/

149.2 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

154.5 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

Crystals; specific optical rotation: -32.5 deg at 20 °C/D (water); +16.0 deg at 20 °C/D (4 N HCl) /l-form/

Crystals; specific optical rotation: +32.2 deg at 20 °C/D (water) /d-form/

Danger

H226 (33.3%): Flammable liquid and vapor [Warning Flammable liquids]

P210, P233, P240, P241, P242, P243, P261, P264, P264+P265, P270, P271, P280, P301+P316, P301+P317, P303+P361+P353, P304+P340, P305+P351+P338, P317, P321, P330, P337+P317, P370+P378, P403+P235, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

5-HTP may decrease the effectiveness of methylsergide and cyproheptadine.

DURATION OF /SRP:CNS DEPRESSION/ INDUCED BY ETHANOL (3.0 G/KG, IP) IN MICE OF BOTH SEXES WAS INCR BY PRETREATMENT WITH 5-HYDROXYTRYPTOPHAN (60 MG/KG, IP).

Concurrent use of 5-HTP with a selective serotonin reuptake inhibitors (SSRI) /citalopram, fluvoxamine maleate, fluoxetine, paroxetine, sertraline, venlafaxine/ may potentiate the antidepressant effect of the SSRI and may also increase the risk of adverse reactions.

Phenoxybenzamine inhibits the conversion of 5-HTP to serotonin.

For more Interactions (Complete) data for 5-HYDROXYTRYPTOPHAN (16 total), please visit the HSDB record page.

5-Hydroxy-L-tryptophan is the immediate precursor of the neurotransmitter serotonin. An accumulation of 5-hydroxy-L-tryptophan in cerebrospinal fluid occurs in aromatic L-amino acid decarboxylase deficiency, accompanied by an increased excretion in the urine of the patients, which are indicative of the disorder. 5-Hydroxy-L-tryptophan easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. Supplementation with 5-hydroxy-L-tryptophan is hypothesized to normalize serotonin synthesis, which is putatively related to its antidepressant properties.

/SIGNS AND SYMPTOMS/ The most common side effects are nausea, vomiting, fatigue/sleepiness. Adverse events appear to be dose related to some degree.

/SIGNS AND SYMPTOMS/ Eosinophilia and eosinophilia-myalgia syndrome (EMS) have been reported in those taking 5-HTP. The eosinophilia myalgia syndrome is similar to that caused by L-tryptophan and was linked to contaminants in the 5-HTP preparation, rather than 5-HTP itself. Changing the 5-HTP lot in one group of patients resolved the eosinophilia. A scleroderma-like skin condition has been reported in some taking a combination of 5-HTP and carbidopa.

/SIGNS AND SYMPTOMS/ Other reported side effects, include nausea, diarrhea, loss of appetite, vomiting and difficult breathing. Neurological side effects, including dilation of the pupils, abnormally sensitive reflexes, loss of muscle coordination and blurring of vision, have been reported in those taking large doses of 5-HTP. Cardiac dysrhythmias have also been reported.

/SIGNS AND SYMPTOMS/ Large doses of 5-HTP may significantly increase serum levels of serotonin, and theoretically, this may result in the serotonin syndrome. Symptoms and signs of the serotonin syndrome, include confusion, agitation, diaphoresis, tachycardia, myoclonus and hyperreflexia. In addition, hypertension, coma/unresponsiveness, seizures, and death may occur if the syndrome is not promptly recognized and treated. There are no reports of serotonin syndrome occurring with use of 5-HTP in humans. However, it could occur and the combination of 5-HTP with another serotonergic agent can increase the risk of it occurring.

/OTHER TOXICITY INFORMATION/ ... Members of a family who became ill after exposure to L-5-HTP were evaluated at the National Institutes of Health. Data from patients with extended exposure to L-5-HTP were also examined. Samples of L-5-HTP were examined using high performance liquid chromatography ... One member of the family had eosinophiliamyalgia syndrome (EMS), and 2 others had eosinophilia. No patient in the other group reviewed developed the syndrome, although 2 patients developed eosinophilia. The L-5-HTP used by the family contained an impurity not present in samples from the other patient group. After replacement with L-5-HTP not containing this impurity, eosinophilia in 2 family members resolved.

/LABORATORY ANIMALS: Acute Exposure/ Administration of L-5-hydroxytryptophan (25 ug/kg, sc), the immediate precursor of serotonin, to rats induces drinking and increases tail skin temperature. Decreases in both the metabolic rate (rate of oxygen consumption) and colonic temperature also occur. These responses are similar to those observed following acute administration of angiotensin II. However, both drinking and the increase in tail skin temperature are unaffected by prior administration of the non-peptide angiotensin II, AT-1 receptor antagonist, losartan potassium, but are partially attenuated by the beta-adrenoceptor antagonist, propranolol. This suggests that the responses are independent of the angiotensin AT-1 receptor but may be mediated, in part at least, by the beta-adrenoceptor.

/LABORATORY ANIMALS: Neurotoxicity/ 5-HYDROXYTRYPTOPHAN INDUCES CHARACTERISTIC BEHAVIORAL SYNDROME OF ALTERED MOTOR ACTIVITY WITH MUSCLE JERKING IN GUINEA PIGS, OCCURRING SYNCHRONOUSLY IN FORELIMBS & HINDLIMBS. NO EEG CHANGES WERE SEEN PRECEDING MUSCLE JERKS.

/LABORATORY ANIMALS: Neurotoxicity/ The acute administration of 5-HTP was reported to block in undernourished dominant pigeons the aggressive attacks induced in a submissive partner by food competition. In the present study, undernourished pigeons with previously consolidated dominance were submitted to subchronic and chronic 5-HTP treatment. Adult males (n = 28) were kept at 80% of their body weight by a restricted diet. These were divided in pairs made of a previously ranked dominant subject (total time spent in aggression higher than 200 sec/20 min) and a submissive one of similar body weight (time spent in aggression between 90 and 150 sec/20 min). The same pairs were exposed to a daily 20 min interaction during each experiment in an observation chamber bearing a central feeder. The time spent in aggressive behavior, feeder control behavior and eating behavior was recorded. Intratest body weight gain was also recorded. In Experiment 1, 8 pairs of pigeons were exposed to a daily trial for 4 successive days (pretreatment-scores). The dominant subjects were then injected subcutaneously, 30 min before trials, with 7.5 mg/kg 5-HTP from day 5 to day 8 (Treatment scores). The Recovery scores were obtained through a 4-trial post-treatment schedule. In Experiment 2 different pigeons were used. The pretreatment and recovery scores were obtained according to a 16-trial schedule (16 days). Both 4-day (subchronic) and 16-day (chronic) 5-HTP treatments attenuated aggression by the dominant subjects and reduced their intra-test body weight gain but did not decrease dominance for feeder control. The recovery scores of total aggression in subchronic experiments returned to pretreatment scores. In chronic experiments, instead, the recovery scores of aggression remained lower than pretreatment scores, whereas body-weight-gain scores came back to pretreatment values. This suggests that dominant subjects submitted to chronic 5-HTP might have learned to maintain dominance and feeder control in a virtual absence of aggressive behavior.

/OTHER TOXICITY INFORMATION/ Ip injection of 5-hydroxytryptophan enhanced electroacupuncture analgesia in rats.

For more Non-Human Toxicity Excerpts (Complete) data for 5-HYDROXYTRYPTOPHAN (7 total), please visit the HSDB record page.

5-HTP should be avoided by pregnant women and nursing mothers.

5-HTP should be avoided by those with ischemic heart disease (history of myocardial infarction, angina pectoris, documented silent ischemia), coronary artery spasm (e.g., Prinzmetal's angina), uncontrollable hypertension and any other significant cardiovascular disease.

... Timed-pregnant CD-1 mice were dosed by gavage (po) on gestational days 6-15 with L-5-Hydroxytryptophan (HTP) (0.0, 50.0, 150.0, 300.0 or 450.0 mg/kg/day) in corn oil. ... Dams were weighed on gestational days 0, 6-15 (prior to daily dosing) & 17 (immediately after sacrifice) & were also observed for clinical signs of toxicity. At sacrifice on gestational day 17, dams were evaluated for body weight, liver weight, gravid uterine weight & status of uterine implantation sites (i.e., sites, resorptions, dead fetuses, live fetuses). Live fetuses were dissected from the uterus & evaluated for live litter size, body weight, sex & gross morphological abnormalities. All live fetuses were examined for visceral malformations employing the Staples' fresh tissue dissection method. Half of the fetuses were decapitated prior to dissection & the heads were fixed in Bouin's solution for free-hand sectioning & exam (Wilson's technique). All fetal carcasses were stained with Alizarin Red S & examined for skeletal malformations. The maternal mortality rate in the present study was 0.0% for all dose groups. A significant dose-response trend (p<0.05) for reduction in maternal body weight was observed on gestational days 11, 15 & 17, but not on gestational days O or 6 (immediately prior to onset of dosing), with no significant pairwise comparisons. There was also a downward significant trend for maternal weight gain during gestation period & during treatment period but no significant pairwise comparisons. At sacrifice on gestational day 17 a dose-response trend was evident for reduction in maternal liver weight, with the values from L-5-Hydroxytryptophan-150 & L-5-Hydroxytryptophan-450 dams significantly reduced relative to controls. Relative maternal liver weight & absolute & relative kidney weight values did not vary among dose groups. The following clinical signs: maternal weight loss of 1 gram or more/day (considered to be an indication of toxicity in individual dams), alopecia, piloerection, rough coat, unthriftiness, diarrhea & hyperactivity were all exhibited by dams in a clear dose-dependent manner. Data concerning the status of uterine implantation sites exhibited a variable response. There were no statistically significant dose- related differences for number of implantation sites/dam, number or % of resorptions, fetal deaths, nonlive fetuses (dead plus resorbed) or affected fetuses (non-live plus malformed)/litter, or for the number or proportion of litters with one or more resorptions, fetal deaths, non-live, or affected fetuses. In live litters (i.e. litters with one or more live fetuses) there was no difference in the number of live fetuses/litter or in the proportion of males to females/litter across treatment groups. Body weights of live fetuses in toto, or for male & female fetuses separately, from L-5-Hydroxytryptophan-treated litters exhibited a significant downward dose-response trend, with values from L-5-Hydroxytryptophan-300 & L-5-Hydroxytryptophan-450 dams significantly reduced relative to controls. There were no significant differences among treated & control litters in the number or percentages of males, females or live fetuses malformed nor in the number or percentages of litters with malformed fetuses. Exam of malformation incidence by category produced no evidence of overall dose-response trends, although exencephaly & trilateral open eye were seen in fetuses only from L-5-Hydroxytryptophan-150, L-5-Hydroxytryptophan-300 & L-5-Hydroxytryptophan-450 dose groups. In conclusion, no evidence for teratogenicity of L-5- hydroxytryptophan was seen in pregnant CD-1 mice when administered in corn oil by gavage during the time of organogenesis at doses which produced marginal evidence of maternal toxicity (clinical signs & trends for reduced body weights & weight gain), & evidence of fetal toxicity as indicated by a highly significant dose-response trend toward decreased fetal weight, with significantly lower values in the L-5-Hydroxytryptophan-300 & L-5-Hydroxytryptophan-450 groups relative to controls.

The possible analgesic effect of 5-HTP may be accounted for, in part, by its conversion to serotonin. 5-HTP has also been found to increase plasma beta-endorphin and platelet met-enkephalin levels, which may signify a reinforcing effect upon an endogenous analgesic effect.

The mechanism of the possible antidepressant activity of 5-HTP is accounted for by its conversion to the neurotransmitter serotonin which plays a central role in the affective state. Antidepressants may work by either binding to one or more of the family of serotonin 5-HT receptors (5-HT1 - 5-HT7) or by inhibiting the reuptake of serotonin. ...

5-HTP is transported by the portal circulation to the liver where approximately 25% of an administered dose is metabolized via vitamin B6-dependent L-aromatic amino acid decarboxylase to 5-hydroxytryptamine (5-HT) /serotonin/. 5-HT is subsequently metabolized to 5-hydroxyindole acetaldehyde which is rapidly metabolized to 5-hydroxyindole acetaldehyde which is rapidly metabolized to 5-hydroxyindoleacetic acid (5-HIAA).

5-Hydroxytryptophan is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of vitamin B6. This reaction occurs both in nervous tissue and in the liver.

The immediate precursor in the serotonin synthetic route, 5-hydroxytryptophan (5-HTP), labeled with 11C in the beta position, has become available for studies using positron emission tomography (PET) to examine serotonin formation in human brain. Normalized uptake and intracerebral utilization of tracer amounts of (beta-11C)5-HTP were studied twice in six healthy male volunteers, three of them before and after pharmacological pretreatments ... Pretreatments with benserazide, p-chlorophenylalanine (PCPA), and unlabeled 5-HTP all significantly increased uptake of (beta-11C)5-HTP. The utilization rates in both striatal and frontal cortex were higher than those in the surrounding brain, indicating that PET studies using (beta-11C)5-HTP as a ligand quantitate selective processes in the utilization of 5-HTP.

The efficiency of absorption of 5HTP, as well as its decarboxylation product serotonin, is approximately 47% to 84%. Absorption of 5-HTP occurs by an active transport process. 5-HTP is transported by the portal circulation to the liver where approximately 25% of an administered dose is metabolized ... . 5-HTP that is not metabolized in the liver is transported by the general circulation to the various tissues of the body, including the brain. 5-HTP readily crosses the blood-brain barrier, and is converted to serotonin in brain cells.

Antidepressant; in treatment of myoclonus

MEDICATION

For use as an antidepressant, appetite suppressant, and sleep aid.

Tryptophan, 5-hydroxy-: INACTIVE

PRECURSOR OF SEROTONIN.