Zalsupindole

Clinical data
Other names	ZAL; DLX-001; DLX-1; DLX001; DLX1; AAZ-A-154; AAZ; (R)-5-Methoxy-N,N-dimethyl-α-methylisotryptamine; (R)-5-MeO-α-methyl-isoDMT; (R)-5-MeO-N,N-dimethyl-isoAMT
Routes of administration	Oral[1][2][3]
Drug class	Non-hallucinogenicserotonin5-HT2A receptoragonist;Psychoplastogen
ATC code	None
Identifiers
IUPAC name (2R)-1-(5-methoxy-1H-indol-1-yl)-N,N-dimethylpropan-2-amine
CAS Number	2481740-94-5
PubChemCID	154694212
ChemSpider	129562407
CompTox Dashboard(EPA)	DTXSID901336869
Chemical and physical data
Formula	C14H20N2O
Molar mass	232.327 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN(C)[C@H](C)Cn1ccc2cc(ccc21)OC
InChI InChI=1S/C14H20N2O/c1-11(15(2)3)10-16-8-7-12-9-13(17-4)5-6-14(12)16/h5-9,11H,10H2,1-4H3/t11-/m1/s1 Key:KHEUWLQKCXGVEL-LLVKDONJSA-N

Zalsupindole, also known by its code namesDLX-001 andAAZ-A-154 and as(R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine ((R)-5-MeO-α-Me-isoDMT), is non-hallucinogenicserotonin receptor agonist andpsychoplastogen of theisotryptamine family related topsychedelictryptamines such asdimethyltryptamine (DMT).^{[1][2][4][5][6]} It is under development for the treatment ofmajor depressive disorder and othercentral nervous system disorders.^[2][4] The drug is takenorally.^[1][2][3]

It acts as apartial agonist of the serotonin 5-HT_2A receptor and also interacts with otherserotonin receptors.^[1] The drug activates the serotonin 5-HT_2A receptor with sufficiently highefficacy to promoteneuroplasticity but not with adequate efficacy to cause psychedelic effects.^[1] It does not produce psychedelic-like effects in animals or humans but does produceantidepressant-like effects in animals.^[1][3]

Zalsupindole was first described in thescientific literature by 2021.^[7] It was developed byDavid E. Olson and colleagues at theUniversity of California, Davis andDelix Therapeutics.^[2][4] As of December 2024, it is inphase 1clinical trials and aphase 2 trial is being planned.^[2]

Aphase 1dose-rangingclinical trial found that zalsupindole is non-hallucinogenic in humans across a dose range of 2 to 360 mgorally.^[1][3] Nonetheless, it produced changes inbrain function as measured byquantitative electroencephalography (qEEG).^[3]

Side effects of zalsupindole includedose-dependentnausea,headache, anddizziness.^[3]

Zalsupindole is anon-selectiveserotonin receptor modulator including of theserotonin5-HT_2A receptor.^[1][8] It acts as a low-potency, low-efficacypartial agonist of the serotonin 5-HT_2A receptor, with anEC₅₀Tooltip half-maximal effective concentration of 8,200 nM and anE_maxTooltip maximal efficacy of 17%.^[1] The drug is also a moderate-efficacy partial agonist of the serotonin 5-HT_2C receptor, with anEC₅₀ of 3,300 nM and anE_max of 70%.[1] Other activities have also been reported.^[1] It isselective for theserotonin5-HT₂ receptors over a number of otherreceptors, includingdopamine receptors,adrenergic receptors, and theκ-opioid receptor, among others.^[1][8] The drug is asilent antagonist of the serotonin5-HT_2B receptor, with anIC₅₀Tooltip half-maximal inhibitory concentration of 27,600 nM.^[1][6]

Zalsupindole isorallybioavailable andcentrallypenetrant in animals.^[6] It is apsychoplastogen via activation of the serotonin 5-HT_2A receptor and rapidly and persistently increasesneuroplasticity inpreclinical research.^[1][9][5][6]Animal studies have found that it producesantidepressant-like effects without causingpsychedelic-like effects such as thehead-twitch response.^{[1][7][10][5][6][11]} It does not producehyperlocomotion at therapeutically relevant doses.^[1] In accordance with its serotonin 5-HT_2B receptor antagonism, zalsupindole showed nocardiovascularsafety signals in animals.^[6]

Thepharmacokinetics of zalsupindole have been studied.^[1][3]

Zalsupindole, also known as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine, is asubstituted isotryptaminederivative.^[12][13] It is a combined derivative of5-methoxy-N,N-dimethylisotryptamine (5-MeO-isoDMT) andα-methylisotryptamine (isoAMT).^[12][13] Another related compound is6-methoxy-N,N-dimethylisotryptamine (6-MeO-isoDMT).^[12] Zalsupindole is a close isotryptamineanalogue ofα,N,N,O-tetramethylserotonin (α,N,N,O-TMS or 5-MeO-α,N,N-TMT).^[13]

Zalsupindole was first described in thescientific literature byDavid E. Olson and colleagues in 2021.^[7] It was developed by Olson's lab at theUniversity of California, Davis and at his companyDelix Therapeutics.^[2][4] The drug was initially described under the nameAAZ-A-154 and then by the nameDLX-001 before receiving the namezalsupindole.^[2][4][1]

Zalsupindole is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name.^[14] It is also known by its developmental code namesDLX-001 andAAZ-A-154.^[2][4]

Zalsupindole, as well as related drugs such astabernanthalog (TBG; DLX-007),DLX-159,DLX-2270, andJRT, are licensed byDelix Therapeutics and are being developed for treatment ofneuropsychiatric disorders such asdepression andschizophrenia.^[9][2][4] As of December 2024, zalsupindole is inphase 1clinical trials formajor depressive disorder and othercentral nervous system disorders.^[2][4] Aphase 2 trial is being planned.^[2]

• Substituted isotryptamine
• Non-hallucinogenic 5-HT_2A receptor agonist
• List of investigational hallucinogens and entactogens
• List of investigational antidepressants

• 5-MeO-α-methyl-iso-DMT (AAZ-A-154) - Isomer Design

• Drugs not assigned an ATC code
• 5-HT1D agonists
• 5-HT2B antagonists
• 5-HT2C agonists
• 5-HT3 antagonists
• 5-HT7 agonists
• Designer drugs
• Dimethylamino compounds
• Experimental antidepressants
• Experimental drugs
• Experimental non-hallucinogens
• Isotryptamines
• Methoxy compounds
• Monoamine oxidase inhibitors
• Non-hallucinogenic 5-HT2A receptor agonists
• Psychoplastogens
• Sigma receptor modulators

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