Zalsupindole
Chemical compound
From Wikipedia, the free encyclopedia
Zalsupindole, also known by its code names DLX-001 and AAZ-A-154 and as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine ((R)-5-MeO-α-Me-isoDMT), is non-hallucinogenic serotonin receptor agonist and psychoplastogen of the isotryptamine family related to psychedelic tryptamines such as dimethyltryptamine (DMT).[4][1][2][5][6][7] It is under development for the treatment of major depressive disorder and other central nervous system disorders.[2][5] The drug is taken orally.[4][1][2][3]
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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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| Formula | C14H20N2O |
| Molar mass | 232.327 g·mol−1 |
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It acts as a partial agonist of the serotonin 5-HT2A receptor and also interacts with other serotonin receptors.[4][1] The drug activates the serotonin 5-HT2A receptor with sufficiently high efficacy to promote neuroplasticity but not with adequate efficacy to cause psychedelic effects.[4][1] It does not produce psychedelic-like effects in animals or humans but does produce antidepressant-like effects in animals.[4][1][3]
Zalsupindole was first described in the scientific literature by 2021.[4][8] It was developed by David E. Olson and colleagues at the University of California, Davis and Delix Therapeutics.[4][2][5] As of April 2026, it has successfully completed Phase 1 clinical trials, demonstrating positive safety and biomarker data. The FDA has cleared the Investigational New Drug (IND) application for a Phase 2 trial, which includes a study design for at-home administration.[2][4][9][10]
Use and effects
A phase 1 dose-ranging clinical trial found that zalsupindole is non-hallucinogenic in humans across a dose range of 2 to 360 mg orally.[4][1][3][9] Nonetheless, it produced changes in brain function as measured by quantitative electroencephalography (qEEG).[4][3][9]
Side effects
Side effects of zalsupindole include dose-dependent nausea, headache, and dizziness.[3][9]
Pharmacology
Pharmacodynamics
Zalsupindole is a non-selective serotonin receptor modulator including of the serotonin 5-HT2A receptor.[4][1][11] It acts as a low-potency, low-efficacy partial agonist of the serotonin 5-HT2A receptor, with an EC50 of 8,200 nM and an Emax of 17%.[4][1] The drug is also a moderate-efficacy partial agonist of the serotonin 5-HT2C receptor, with an EC50 of 3,300 nM and an Emax of 70%.[4][1] Other activities have also been reported.[4][1] It is selective for the serotonin 5-HT2 receptors over a number of other receptors, including the serotonin 5-HT1A receptor, dopamine receptors, adrenergic receptors, and the κ-opioid receptor, among others.[4][1][11] The drug is a silent antagonist of the serotonin 5-HT2B receptor, with an IC50 of 27,600 nM.[4][1][7]
Zalsupindole is orally bioavailable and centrally penetrant in animals.[4][7] It is a psychoplastogen via activation of the serotonin 5-HT2A receptor and rapidly and persistently increases neuroplasticity in preclinical research.[4][1][12][6][7] The serotonin 5-HT2A receptor antagonist ketanserin abolishes the psychoplastogenic effects of zalsupindole.[4] Zalsupindole produces comparable psychoplastogenic effects to serotonergic psychedelics like psilocin and dimethyltryptamine (DMT) as well as to the dissociative ketamine.[4] Animal studies have found that the drug produces antidepressant-like effects without causing psychedelic-like effects such as the head-twitch response.[4][1][8][13][6][7][14] It does not produce hyperlocomotion at therapeutically relevant doses.[1] In accordance with its serotonin 5-HT2B receptor antagonism, zalsupindole showed no cardiovascular safety signals in animals.[4][7]
Pharmacokinetics
The pharmacokinetics of zalsupindole have been studied.[4][1][3]
Chemistry
Zalsupindole, also known as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine, is a substituted isotryptamine derivative.[4][15][16] It is a combined derivative of 5-methoxy-N,N-dimethylisotryptamine (5-MeO-isoDMT) and α-methylisotryptamine (isoAMT).[15][16] Another related compound is 6-methoxy-N,N-dimethylisotryptamine (6-MeO-isoDMT).[15] Zalsupindole is a close isotryptamine analogue of α,N,N,O-tetramethylserotonin (α,N,N,O-TMS or 5-MeO-α,N,N-TMT).[16]
Synthesis
The chemical synthesis of zalsupindole has been described.[4][13]
History
Zalsupindole was first described in the scientific literature by David E. Olson and colleagues in 2021.[4][8] It was developed by Olson's lab at the University of California, Davis and at his company Delix Therapeutics.[4][2][5] The drug was first synthesized in 2019.[4] It was initially described under the name AAZ-A-154 and then by the name DLX-001 before receiving the name zalsupindole.[4][2][5][1]
Society and culture
Research
Zalsupindole, as well as related drugs such as tabernanthalog (TBG; DLX-007), DLX-159, DLX-2270, and JRT, are licensed by Delix Therapeutics and are being developed for treatment of neuropsychiatric disorders such as depression and schizophrenia.[4][12][2][5] As of January 2026, zalsupindole is in phase 1 clinical trials for major depressive disorder and other central nervous system disorders.[2][5] Phase 1a and 1b trials have been completed and results reported.[4][2][5][9] A phase 2 trial is being planned and has been cleared by the FDA for at home administration.[2][4][9]