Α-Methyl-5-hydroxytryptophan

α-Methyl-5-hydroxytryptophan
Clinical data
Other namesalpha-Methyl-5-hydroxytryptophan; alpha-Methyl-L-5-hydroxytryptophan; α-Me-5-HTP; α-Methyl-5-HTP; αM-5-HTP; alpha-Me-5-HTP; alpha-Methyl-5-HTP
Drug classTyrosine hydroxylase inhibitor; Serotonin receptor agonist
Identifiers
IUPAC name
  • (2S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)-2-methylpropanoic acid
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H14N2O3
Molar mass234.255 g·mol−1
3D model (JSmol)
SMILES
  • C[C@](CC1=CNC2=C1C=C(C=C2)O)(C(=O)O)N
InChI
  • InChI=1S/C12H14N2O3/c1-12(13,11(16)17)5-7-6-14-10-3-2-8(15)4-9(7)10/h2-4,6,14-15H,5,13H2,1H3,(H,16,17)/t12-/m0/s1
  • Key:QNQKTYDMWUGLPA-LBPRGKRZSA-N

α-Methyl-5-hydroxytryptophan (α-Me-5-HTP) is a synthetic tryptamine derivative, an artificial amino acid, and a prodrug of α-methylserotonin.[1][2] It is the α-methylated derivative of 5-hydroxytryptophan (5-HTP), while αMS is the α-methylated analogue of serotonin.[1][2] Along with α-methyltryptophan (α-MTP), α-Me-5-HTP has been suggested for potential therapeutic use in the treatment of conditions thought by some authors to be related to serotonin deficiency, such as depression.[2]

αMS is a non-selective serotonin receptor agonist, including of the serotonin 5-HT2 receptors, and has been described as a "substitute neurotransmitter" of serotonin.[2][3][4][5] However, whereas αMS itself is too hydrophilic to efficiently cross the blood–brain barrier, thus being peripherally selective, α-MTP and α-Me-5-HTP are able to cross the blood–brain barrier and, following transformation, deliver αMS into the brain.[2][6] Besides αMS, α-methylmelatonin can be formed in small amounts from α-Me-5-HTP.[7]

In addition to their serotonergic activity, α-Me-5-HTP and αMS have been found to act as norepinephrine releasing agents similarly to α-methylphenylalanine and to other α-alkylated tryptamines.[8][9][10] Moreover, α-Me-5-HTP is also a tyrosine hydroxylase inhibitor similarly to α-methyltyrosine, as well as an aromatic L-amino acid decarboxylase (AAAD) inhibitor, and has been found to deplete levels of brain norepinephrine in animals, although not levels of brain dopamine.[2][11][8][12][13] Because of these actions, α-Me-5-HTP shows antihypertensive effects and reduces locomotor activity in animals.[12]

See also

References

  1. 1 2 "alpha-Methyl-5-hydroxytryptophan". PubChem. Retrieved 8 October 2024.
  2. 1 2 3 4 5 6 Sourkes TL (1991). "Alpha-methyltryptophan as a therapeutic agent". Prog Neuropsychopharmacol Biol Psychiatry. 15 (6): 935–938. doi:10.1016/0278-5846(91)90020-2. PMID 1763198.
  3. ↑ Maroteaux L, Ayme-Dietrich E, Aubertin-Kirch G, Banas S, Quentin E, Lawson R, et al. (February 2017). "New therapeutic opportunities for 5-HT2 receptor ligands" (PDF). Pharmacol Ther. 170: 14–36. doi:10.1016/j.pharmthera.2016.10.008. PMID 27771435. alpha-methyl-5-HT is a non-selective nearly full agonist at 5-HT2 receptors with similar affinity to 5-HT2A 5-HT2B and 5-HT2C receptors (Jerman, et al., 2001; Knight, et al., 2004; Porter, et al., 1999).
  4. ↑ Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, et al. (2001). "Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists". Pharmacol Biochem Behav. 69 (3–4): 643–652. doi:10.1016/s0091-3057(01)00552-4. PMID 11509227.
  5. ↑ Ismaiel AM, Titeler M, Miller KJ, Smith TS, Glennon RA (February 1990). "5-HT1 and 5-HT2 binding profiles of the serotonergic agents alpha-methylserotonin and 2-methylserotonin". Journal of Medicinal Chemistry. 33 (2): 755–758. doi:10.1021/jm00164a046. PMID 2299641.
  6. ↑ Diksic M, Young SN (September 2001). "Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan". J Neurochem. 78 (6): 1185–1200. doi:10.1046/j.1471-4159.2001.00536.x. PMID 11579128.
  7. ↑ Montine TJ, Missala K, Sourkes TL (January 1992). "Alpha-methyltryptophan metabolism in rat pineal gland and brain". J Pineal Res. 12 (1): 43–48. doi:10.1111/j.1600-079x.1992.tb00024.x. PMID 1564632.
  8. 1 2 Lahti RA, Platz PA, Heinzelman RV (July 1969). "Effects of alpha-methyl-5-hydroxytryptophan and alpha-methyl-5-hydroxytryptamine on norepinephrine in mouse myocardium". Biochem Pharmacol. 18 (7): 1601–1608. doi:10.1016/0006-2952(69)90147-6. PMID 5306701.
  9. ↑ Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB (October 2014). "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl). 231 (21): 4135–4144. doi:10.1007/s00213-014-3557-7. PMC 4194234. PMID 24800892.
  10. ↑ Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
  11. ↑ Murphy GF, Sourkes TL (May 1961). "The action of antidecarboxylases on the conversion of 3,4-dihydroxyphenylalanine to dopamine in vivo". Arch Biochem Biophys. 93 (2): 338–343. doi:10.1016/0003-9861(61)90276-4. PMID 13726974.
  12. 1 2 Tabei R, Spector S, Louis WJ, Sjoerdsma A (July 1969). "Antihypertensive and noradrenaline-depleting effects of alpha-methyl-5-hydroxytryptophan in the rat". Eur J Pharmacol. 7 (1): 39–44. doi:10.1016/0014-2999(69)90160-5. PMID 5307150.
  13. ↑ Dominic JA, Moore KE (December 1969). "Behavioral and catecholamine depleting effects of alpha-methyl-5-hydroxytryptophan". Eur J Pharmacol. 8 (3): 292–295. doi:10.1016/0014-2999(69)90037-5. PMID 5308817.
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