5-Methoxyharmalan

5-Methoxyharmalan, also known as 5-methoxy-1-methyl-4,9-dihydro-3H-β-carboline, is a serotonin receptor modulator of the β-carboline family.^[1][2][3] It is a cyclized tryptamine analogue of 4-MeO-DMT and a positional isomer of 6-methoxyharmalan and harmaline (7-methoxyharmalan).^[2][3]

5-Methoxyharmalan

Clinical data
Other names	5-MeO-harmalan; 5-OMe-harmalan; 5-Methoxy-1-methyl-4,9-dihydro-3H-β-carboline
Drug class	Serotonin receptor modulator
ATC code	None
Identifiers
IUPAC name 5-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole
PubChem CID	137193151
ChemSpider	62968019
ChEMBL	ChEMBL4784346
Chemical and physical data
Formula	C13H14N2O
Molar mass	214.268 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=NCCC2=C1NC3=C2C(=CC=C3)OC
InChI InChI=1S/C13H14N2O/c1-8-13-9(6-7-14-8)12-10(15-13)4-3-5-11(12)16-2/h3-5,15H,6-7H2,1-2H3 Key:RFGOJFHLZUEUIV-UHFFFAOYSA-N

Pharmacology

The drug shows high affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = 86–137 nM and 69 nM, respectively).^[2][3] It had higher affinity for these receptors than any other assessed β-carboline, with 1.7–4.6-fold, 57–58-fold, and >73–116-fold the affinity of harmine, harmaline, and tetrahydroharmine for the serotonin 5-HT_2A receptor, respectively.^[2][3] However, like harmaline and 6-methoxyharmalan, 5-methoxyharmalan showed no agonist or antagonist activity at the serotonin 5-HT_2A receptor in terms of phosphatidylinositol (PI) hydrolysis in vitro at concentrations of up to 10,000 nM (and harmaline further showed no agonist activity in this assay at up to 20,000 nM).^[2] It is unclear whether the serotonin 5-HT_2A receptor is involved in the hallucinogenic or other psychoactive effects of β-carbolines.^[2][3]

5-Methoxyharmalan showed no affinity for the melatonin receptors.^[4] The 1-demethyl analogue of 5-methoxyharmalan shows high affinity for the imidazoline I₂ receptor and the α₂ receptor, whereas 5-methoxyharmalan itself was not assessed.^[5]

History

5-Methoxyharmalan was first described in the scientific literature by 1993.^[4]

See also

• Substituted β-carboline
• 6-Methoxyharmalan
• Harmaline (7-methoxyharmalan)