Oxitriptan

Identification

Name
Oxitriptan
Accession Number
DB02959  (EXPT01780)
Type
Small Molecule
Groups
Approved, Investigational, Nutraceutical
Description

5-Hydroxytryptophan (5-HTP), also known as oxitriptan (INN), is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan. 5-HTP is sold over-the-counter in the United Kingdom, United States and Canada as a dietary supplement for use as an antidepressant, appetite suppressant, and sleep aid, and is also marketed in many European countries for the indication of major depression under trade names like Cincofarm, Levothym, Levotonine, Oxyfan, Telesol, Tript-OH, and Triptum. Several double-blind placebo-controlled clinical trials have demonstrated the effectiveness of 5-HTP in the treatment of depression, though a lack of high quality studies has been noted. More and larger studies are needed to determine if 5-HTP is truly effective in treating depression.

Structure
Thumb
Synonyms
  • 5-Hydroxy-L-Tryptophan
  • 5-Hydroxytryptophan L-form
  • Cincofarm
  • Hydroxy-5 L-tryptophane
  • L-5-Hydroxytryptophan
  • Levothym
  • Oxitriptan
  • Tript-OH
International/Other Brands
Levothym (Lundbeck) / Quietim (Nativelle)
Categories
UNII
C1LJO185Q9
CAS number
4350-09-8
Weight
Average: 220.2246
Monoisotopic: 220.08479226
Chemical Formula
C11H12N2O3
InChI Key
LDCYZAJDBXYCGN-VIFPVBQESA-N
InChI
InChI=1S/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)/t9-/m0/s1
IUPAC Name
(2S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
SMILES
N[[email protected]@H](CC1=CNC2=C1C=C(O)C=C2)C(O)=O

Pharmacology

Indication

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

Structured Indications
Not Available
Pharmacodynamics

The psychoactive action of 5-HTP is derived from its effect on the production of serotonin in central nervous system tissue. More specifically, 5-HTP increases the production of serotonin.

Mechanism of action
TargetActionsOrganism
UTryptophan--tRNA ligase 2Not AvailableDeinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

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.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Tryptophan MetabolismMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Oxitriptan.Approved
Food Interactions
Not Available

References

Synthesis Reference

British Patent 845,034.

General References
  1. Turner EH, Blackwell AD: 5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin. Med Hypotheses. 2005;65(1):138-44. [PubMed:15893130]
  2. Shaw K, Turner J, Del Mar C: Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. [PubMed:11869656]
  3. Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M: Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982 Oct;32(5):803-11. [PubMed:6983619]
  4. Nakatani Y, Sato-Suzuki I, Tsujino N, Nakasato A, Seki Y, Fumoto M, Arita H: Augmented brain 5-HT crosses the blood-brain barrier through the 5-HT transporter in rat. Eur J Neurosci. 2008 May;27(9):2466-72. doi: 10.1111/j.1460-9568.2008.06201.x. [PubMed:18445233]
  5. Bouchard S, Roberge AG: Biochemical properties and kinetic parameters of dihydroxyphenylalanine--5-hydroxytryptophan decarboxylase in brain, liver, and adrenals of cat. Can J Biochem. 1979 Jul;57(7):1014-8. [PubMed:39668]
  6. Amamoto T, Sarai K: On the tryptophan-serotonin metabolism in manic-depressive disorders. Changes in plasma 5-HT and 5-HIAA levels and urinary 5-HIAA excretion following oral loading of L-5HTP in patients with depression. Hiroshima J Med Sci. 1976 Sep;25(2-3):135-40. [PubMed:1088369]
  7. Magnussen I, Jensen TS, Rand JH, Van Woert MH: Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man. Acta Pharmacol Toxicol (Copenh). 1981 Sep;49(3):184-9. [PubMed:6175178]
  8. Birdsall TC: 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. [PubMed:9727088]
  9. Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H, Gauthier S, Osterland CK: Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med. 1980 Oct 2;303(14):782-7. [PubMed:6997735]
  10. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V: Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990 May-Jun;18(3):201-9. [PubMed:2193835]
  11. Trouillas P, Serratrice G, Laplane D, Rascol A, Augustin P, Barroche G, Clanet M, Degos CF, Desnuelle C, Dumas R, et al.: Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Arch Neurol. 1995 May;52(5):456-60. [PubMed:7733839]
  12. De Benedittis G, Massei R: Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci. 1985 Jul-Sep;29(3):239-48. [PubMed:3913752]
External Links
Human Metabolome Database
HMDB15571
KEGG Drug
D07339
KEGG Compound
C00643
PubChem Compound
439280
PubChem Substance
46505826
ChemSpider
388413
BindingDB
50403163
ChEBI
58266
ChEMBL
CHEMBL350221
HET
4PQ
Wikipedia
5-Hydroxytryptophan
ATC Codes
N06AX01 — Oxitriptan
PDB Entries
5kpy
MSDS
Download (1.4 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedBasic ScienceIrritable Bowel Syndrome (IBS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)295-297British Patent 845,034.
Predicted Properties
PropertyValueSource
Water Solubility3.63 mg/mLALOGPS
logP-1.6ALOGPS
logP-1.4ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)2.15ChemAxon
pKa (Strongest Basic)9.18ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area99.34 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity58.18 m3·mol-1ChemAxon
Polarizability22.03 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9891
Blood Brain Barrier+0.8916
Caco-2 permeable-0.7442
P-glycoprotein substrateNon-substrate0.5159
P-glycoprotein inhibitor INon-inhibitor0.9971
P-glycoprotein inhibitor IINon-inhibitor0.9838
Renal organic cation transporterNon-inhibitor0.8689
CYP450 2C9 substrateNon-substrate0.8399
CYP450 2D6 substrateNon-substrate0.7445
CYP450 3A4 substrateNon-substrate0.7324
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9642
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8947
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9519
BiodegradationNot ready biodegradable0.7897
Rat acute toxicity2.9260 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9784
hERG inhibition (predictor II)Non-inhibitor0.9299
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (4 TMS)GC-MSsplash10-0006-0390000000-d4e36a90b7591787e67b
GC-MS Spectrum - GC-MS (3 TMS)GC-MSsplash10-0006-1390000000-b0af49def87c0211653c
GC-MS Spectrum - GC-MS (3 TMS)GC-MSsplash10-014i-0390000000-8b7f6cc8f51c032dd86d
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-014i-0390000000-88191cf8140abf0f3205
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0006-0290000000-a30ea02ff8d4d14ba7a4
GC-MS Spectrum - GC-MSGC-MSsplash10-0006-0390000000-d4e36a90b7591787e67b
GC-MS Spectrum - GC-MSGC-MSsplash10-0006-1390000000-b0af49def87c0211653c
GC-MS Spectrum - GC-MSGC-MSsplash10-014i-0390000000-8b7f6cc8f51c032dd86d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0790000000-a699ed429ebd1609f995
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03e9-0900000000-bbd302f8ff188f6cf93d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-053r-0900000000-6cc3ba396b1cfa8db1e6
MS/MS Spectrum - , positiveLC-MS/MSsplash10-053r-2900000000-90a465428eacaced71e2
1H NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as serotonins. These are compounds containing a serotonin moiety, which consists of an indole that bears an aminoethyl a position 2 and a hydroxyl group at position 5.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Tryptamines and derivatives
Direct Parent
Serotonins
Alternative Parents
Indolyl carboxylic acids and derivatives / 3-alkylindoles / L-alpha-amino acids / Hydroxyindoles / 1-hydroxy-2-unsubstituted benzenoids / Aralkylamines / Substituted pyrroles / Heteroaromatic compounds / Amino acids / Monocarboxylic acids and derivatives
show 7 more
Substituents
Serotonin / Indolyl carboxylic acid derivative / Alpha-amino acid / Alpha-amino acid or derivatives / 3-alkylindole / L-alpha-amino acid / Hydroxyindole / Indole / Aralkylamine / 1-hydroxy-2-unsubstituted benzenoid
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
non-proteinogenic L-alpha-amino acid, 5-hydroxytryptophan, hydroxy-L-tryptophan (CHEBI:17780)

Targets

Kind
Protein
Organism
Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422)
Pharmacological action
Unknown
General Function
Tryptophan-trna ligase activity
Specific Function
Catalyzes the formation of 5'adenyl-Trp and tRNA(Trp) but with 5-fold less activity than TrpRS. Increases the solubility of the nitric oxide synthase oxygenase (nos), as well as its affinity for su...
Gene Name
trpS2
Uniprot ID
Q9RVD6
Uniprot Name
Tryptophan--tRNA ligase 2
Molecular Weight
38179.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 03:21