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PubMed · 9727088

5-Hydroxytryptophan: a clinically-effective serotonin precursor.

Abstract

5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

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BibTeXRIS

T C Birdsall. 1998. 5-Hydroxytryptophan: a clinically-effective serotonin precursor.. https://pubmed.ncbi.nlm.nih.gov/9727088/

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5-Hydroxytryptophan toxicosis in dogs: 21 cases (1989-1999).

OBJECTIVE: To determine epidemiologic characteristics, clinical findings, and treatment outcome of 5-hydroxytryptophan (5-HTP) toxicosis in dogs. DESIGN: Retrospective study. ANIMALS: 21 dogs with evidence of accidental 5-HTP ingestion. PROCEDURE: Information was retrieved from the National Animal Poison Control Center database. Records of dogs ingesting 5-HTP between January 1989 and February 1999 were reviewed for information on signalment, dose ingested, clinical signs (onset, severity, duration), treatments administered, and outcome. RESULTS: Clinical signs of toxicosis developed in 19 of 21 (90%) dogs. Neurologic signs included seizures (9 dogs), depression (6), tremors (5), hyperesthesia (5), and ataxia (4). Gastrointestinal tract signs included vomiting or diarrhea (12 dogs), signs of abdominal pain (3), and hypersalivation (2). Other clinical signs were hyperthermia (7 dogs) and transient blindness (3). Three dogs died. No important clinical laboratory or necropsy findings were reported. The doses of 5-HTP ingested ranged from 2.5 to 573 mg/kg (1.1 to 260 mg/lb) of body weight; the minimum toxic dose reported in our study was 23.6 mg/kg (10.7 mg/lb), and the minimum lethal dose was 128 mg/kg (58.1 mg/lb). Onset of signs ranged from 10 minutes to 4 hours after ingestion, and signs lasted up to 36 hours. Of 17 dogs with clinical signs of toxicosis that received treatment, 16 recovered; treatment consisted of decontamination, seizure control, thermoregulation, fluid therapy, and supportive care. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of 5-HTP in dogs can result in a potentially life-threatening syndrome resembling serotonin syndrome in humans, which requires prompt and aggressive care.

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Intracranial self-stimulation increases differentially in vivo hydroxylation of tyrosine but similarly in vivo hydroxylation of tryptophan in rat medial prefrontal cortex, nucleus accumbens and striatum.

We have examined using microdialysis the effect of intracranial self-stimulation (ICSS) on the in vivo hydroxylation rate of tyrosine and tryptophan in the medial prefrontal cortex (mPFC), nucleus accumbens (NAC) and striatum (STR). A decarboxylase inhibitor NSD-1015 was included in the perfusate, which enabled the simultaneous measurement of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) as an index of the in vivo hydroxylation level of tyrosine and tryptophan. When rats were exposed to 1 h of ICSS at the medial forebrain bundle (MFB), their extracellular levels of DOPA significantly increased in the mPFC, NAC and STR, but with a different magnitude and time course. The same stimulation produced a delayed increase in extracellular 5-HTP, compared to DOPA, in these brain regions. The profile of 5-HTP response demonstrated no apparent difference among the regions. These findings indicate that ICSS of the MFB can increase differentially the in vivo hydroxylation of tyrosine but similarly the in vivo hydroxylation of tryptophan in the mPFC, NAC and STR.

5-Hydroxytryptophan↗

Diminished central fatigue by inhibition of the L-system transporter for the uptake of tryptophan.

Nagase genetically analbuminemic rats (NAR) were run to fatigue. Administration of branched chain amino acids (BCAA) before exhaustive exercise, resulted in a post-fatigue decreased tryptophan uptake (-22%, p < 0.05) and 5-hydroxytryptophan (5-HTP) uptake (-29%, p < 0.01) into the synaptosomes isolated from the striatum when compared with saline administration. At the same time, NAR who received either BCAA or 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH, a specific inhibitor for the L-system transporter) had a considerably prolonged run time to exhaustion (by twofold), compared to those who received either saline or albumin treatments. When classified by run time, it was of interest that, when the data for BCAA and BCH treatments for the longer run time NAR (Group B) was combined, it gave rise to a significant decrease in synaptosomal tryptophan and 5-HTP of a similar magnitude to that observed with BCAA alone. These levels were lower than those observed in NAR in the shorter run time group (Group A) for all treatments. These results support the view that an activated serotonergic function may be involved in central fatigue, which can be diminished by inhibition of the L-system transporter.

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