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| 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-hallucinogenic serotonin 5-HT2A receptor agonist;Psychoplastogen |
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| Chemical and physical data | |
| Formula | C14H20N2O |
| Molar mass | 232.327 g·mol−1 |
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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).[4][1][2][5][6][7] It is under development for the treatment ofmajor depressive disorder and othercentral nervous system disorders.[2][5] The drug is takenorally.[4][1][2][3]
It acts as apartial agonist of the serotonin 5-HT2A receptor and also interacts with otherserotonin receptors.[4][1] The drug activates the serotonin 5-HT2A receptor with sufficiently highefficacy to promoteneuroplasticity but not with adequate efficacy to cause psychedelic effects.[4][1] It does not produce psychedelic-like effects in animals or humans but does produceantidepressant-like effects in animals.[4][1][3]
Zalsupindole was first described in thescientific literature by 2021.[4][8] It was developed byDavid E. Olson and colleagues at theUniversity of California, Davis andDelix Therapeutics.[4][2][5] As of January 2026, it is inphase 1clinical trials and aphase 2 trial is being planned.[2][4][9]
Aphase 1dose-rangingclinical trial found that zalsupindole is non-hallucinogenic in humans across a dose range of 2 to 360 mgorally.[4][1][3][9] Nonetheless, it produced changes inbrain function as measured byquantitative electroencephalography (qEEG).[4][3][9]
Side effects of zalsupindole includedose-dependentnausea,headache, anddizziness.[3][9]
Zalsupindole is anon-selectiveserotonin receptor modulator including of theserotonin5-HT2A receptor.[4][1][10] It acts as a low-potency, low-efficacypartial agonist of the serotonin 5-HT2A receptor, with anEC50Tooltip half-maximal effective concentration of 8,200 nM and anEmaxTooltip maximal efficacy of 17%.[4][1] The drug is also a moderate-efficacy partial agonist of the serotonin 5-HT2C receptor, with anEC50 of 3,300 nM and anEmax of 70%.[4][1] Other activities have also been reported.[4][1] It isselective for theserotonin5-HT2 receptors over a number of otherreceptors, including the serotonin5-HT1A receptor,dopamine receptors,adrenergic receptors, and theκ-opioid receptor, among others.[4][1][10] The drug is asilent antagonist of the serotonin5-HT2B receptor, with anIC50Tooltip half-maximal inhibitory concentration of 27,600 nM.[4][1][7]
Zalsupindole isorallybioavailable andcentrallypenetrant in animals.[4][7] It is apsychoplastogen via activation of the serotonin 5-HT2A receptor and rapidly and persistently increasesneuroplasticity inpreclinical research.[4][1][11][6][7] The serotonin 5-HT2A receptor antagonistketanserin abolishes the psychoplastogenic effects of zalsupindole.[4] Zalsupindole produces comparable psychoplastogenic effects toserotonergic psychedelics likepsilocin anddimethyltryptamine (DMT) as well as to thedissociativeketamine.[4]Animal studies have found that the drug producesantidepressant-like effects without causingpsychedelic-like effects such as thehead-twitch response.[4][1][8][12][6][7][13] It does not producehyperlocomotion at therapeutically relevant doses.[1] In accordance with its serotonin 5-HT2B receptor antagonism, zalsupindole showed nocardiovascularsafety signals in animals.[4][7]
Thepharmacokinetics of zalsupindole have been studied.[4][1][3]
Zalsupindole, also known as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine, is asubstituted isotryptaminederivative.[4][14][15] It is a combined derivative of5-methoxy-N,N-dimethylisotryptamine (5-MeO-isoDMT) andα-methylisotryptamine (isoAMT).[14][15] Another related compound is6-methoxy-N,N-dimethylisotryptamine (6-MeO-isoDMT).[14] Zalsupindole is a close isotryptamineanalogue ofα,N,N,O-tetramethylserotonin (α,N,N,O-TMS or 5-MeO-α,N,N-TMT).[15]
Thechemical synthesis of zalsupindole has been described.[4][12]
Zalsupindole was first described in thescientific literature byDavid E. Olson and colleagues in 2021.[4][8] It was developed by Olson's lab at theUniversity of California, Davis and at his companyDelix Therapeutics.[4][2][5] The drug wasfirstsynthesized in 2019.[4] It was initially described under the nameAAZ-A-154 and then by the nameDLX-001 before receiving the namezalsupindole.[4][2][5][1]
Zalsupindole is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name.[4][16] It is also known by its developmental code namesDLX-001 andAAZ-A-154.[4][2][5]
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.[4][11][2][5] As of January 2026, zalsupindole is inphase 1clinical trials formajor depressive disorder and othercentral nervous system disorders.[2][5] Phase 1a and 1b trials have been completed and results reported.[4][2][5][9] Aphase 2 trial is being planned.[2][4][9]
