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SNTX-2643

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SNTX-2643
Clinical data
Other namesSNTX2643; SENS-01; SENS01
Routes of
administration		Oral[1][2]
Drug classAtypical serotonin reuptake inhibitor[1]
ATC code
  • None
Pharmacokinetic data
Onset of actionRapid[1][3]
Peak: 1.5–2.0 hours[2]
Elimination half-life3.9–5.7 hours[2]
Duration of action≥24 hours[4]

SNTX-2643, formerly known as SENS-01, is an atypical serotonin reuptake inhibitor (SRI) derived from Sceletium tortuosum (kanna). It is under development for the treatment of social anxiety disorder, as well as other anxiety disorders and depressive disorders.[5][6][7][1][8] It is described as a novel/first-in-class and fast-acting anxiolytic with less sedation.[1][9][3][8] The drug is administered orally.[1]

Side effects

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Side effects of SNTX-2643 include nausea, vomiting, headache, dizziness, and hypotension.[2] No indications of sedation, dissociation, or misuse-related side effects were observed.[2][4]

Pharmacology

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Pharmacodynamics

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SNTX-2643 acts as a selective atypical serotonin reuptake inhibitor (SRI).[1][3][8][2] Specifically, it binds to an allosteric site on the serotonin transporter (SERT), rather than to the orthosteric site targeted by serotonin and classical selective serotonin reuptake inhibitors (SSRIs).[1] In addition, SNTX-2643 stabilizes the SERT in an inward-open conformation, as opposed to the outward-open conformation of SSRIs.[2] It also acts in an uncompetitive fashion, in contrast to SSRIs.[2] Among the only other known SRIs to stabilize the SERT in the inward-open conformation include ibogaine and noribogaine, as well as novel lesser-known compounds like ZINC000443438219.[10][11][12][13]

Sceletium tortuosum (kanna) acts similarly to SNTX-2643 via its primary alkaloid constituent, mesembrine,[14] but SNTX-2643 is a synthetic derivative with improved drug-like properties.[1] Unlike SSRIs, which typically require 4 to 6 weeks of administration to achieve therapeutic benefits, kanna is reported to have a rapid calming effect within 30 to 60 minutes of ingestion.[1][3][14] The precise mechanism underlying these differences remains unclear, but appears to involve distinct downstream kinase-mediated signaling pathways.[1]

SNTX-2643 has been found to produce a measurable electroencephalogram (EEG) response in humans and to blunt EEG and autonomic changes induced by a psychological stressor in humans.[2][4] These effects were present at both 2 hours and 24 hours post-dose.[2][4]

Pharmacokinetics

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The median time to peak levels of SNTX-2643 is 1.5 to 2.0 hours and its median elimination half-life is 3.9 to 5.7 hours.[2]

Chemistry

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The chemical structure of SNTX-2643 has not yet been publicly disclosed.[5] However, mesembrine analogues acting on the serotonin transporter (SERT) with enhanced drug-like properties were patented by Sensorium Therapeutics in 2025.[15]

Development

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SNTX-2643 is being developed by Sensorium Therapeutics.[5][6][1] As of August 2025, it is undergoing phase 1 clinical trials.[1][3][16] Although listed on Psychedelic Alpha's drug development tracker, SNTX-2643 is not itself a psychedelic.[7] Its inclusion reflects its action on the serotonin system rather than any psychedelic effects.[1][7] Phase 1 findings were released in September 2026.[2]

See also

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References

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  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Cross R (19 August 2025). "Exclusive: Sensorium raises $25M to test succulent-derived drug for anxiety". Endpoints News. The company zeroed in on a molecule derived from a South African succulent known to scientists as Sceletium tortuosum and commonly referred to as kanna. [...] the company's drug "was inspired by a unique natural product found among the diverse molecules," but did not confirm if it came from mesembrine. Chewing kanna is linked to rapid calming action within 30 to 60 minutes, [...] Other researchers have previously shown that kanna inhibits the serotonin transporter, an important protein that moves serotonin in and out of the junctions between brain cells. Antidepressants called selective serotonin reuptake inhibitors (SSRIs) also block the serotonin transporter, but typically take four to six weeks for their effects to kick in, creating a puzzle about why the succulent compound worked so quickly. "We were convinced, quite frankly, that it must be hitting some target that we don't know about," Hooker said. "And we went deep. We looked at many hundreds, if not a thousand or more targets." It turned out that the molecule was binding to the serotonin transporter — a bit of a disappointment at first, given the startup's novel mechanism mandate. However, while SSRIs directly block the ability of serotonin to bind to the transporter, Hooker said he was surprised to find that Sensorium's compound binds to a different site on the protein that doesn't compete with serotonin binding. Hooker is writing a paper to describe the mechanism in more detail. The company is also still trying to figure out exactly why touching the transporter differently has such a seemingly rapid action. Early work suggests it is rooted in downstream signaling proteins called kinases that "fundamentally tune the circuit differently," he said. [...] Sensorium has created hundreds of derivatives of the natural molecule to make a version dubbed SNTX-2643, which can be taken orally once a day. Hooker hopes it will provide an alternative to anxiety medications, including SSRIs and benzodiazepines. Hooker declined to say when the Phase 1 study would wrap up.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 Cutler AJ, Brown C, Hooker J, Rosenbaum J (September 2026). The Novel Serotonin Transporter Modulator SNTX-2643: Results from a Pharmacokinetic and Target Engagement Evaluation in Healthy Adults. Psych Congress, 2026 Annual Meeting, September 15-19, 2026, New Orleans, LA.
  3. 1 2 3 4 5 Richmond LM (1 August 2025). "Med Check: FDA Limits Use of Extended-Release Stimulants, Approves New Titration Schedule for Alzheimer's Drug, and More". Psychiatric News. 60 (8) appi.pn.2025.08.8.2. doi:10.1176/appi.pn.2025.08.8.2. ISSN 0033-2704. Retrieved 27 September 2025. The FDA on July 8 cleared the Investigational New Drug application for Sensorium Therapeutics' anxiety candidate SNTX-2643 a first-in-class precision serotonin modulator. Dosing in human participants will begin in third quarter 2025, the company said in a media release. The company believes that the potential drug will differentiate from benzodiazepine-like drugs with a rapid onset of action, fewer off-target side effects, and less sedation. The compound acts on serotonin through a unique pharmacology that is distinct from SSRIs, which are limited by delayed onset and can paradoxically increase acute anxiety in the early stages of treatment. "A fast-acting, well-tolerated anxiolytic would be an important innovation for the hundreds of millions worldwide living with anxiety disorders," said Maurizio Fava, M.D., Sensorium scientific adviser and chair of psychiatry at Mass General Brigham Academic Medical Centers. "FDA clearance of SNTX-2643 moves us one step closer to that goal."
  4. 1 2 3 4 Brown C (21 September 2026). "Phase 1 Data: SNTX-2643 Blunts the Brain's Stress Response After a Single Dose". Psychiatric Times. Retrieved 19 October 2026.
  5. 1 2 3 "SENS 01". AdisInsight. 28 October 2024. Retrieved 17 February 2025.
  6. 1 2 "Delving into the Latest Updates on SENS-01 with Synapse". Synapse. 23 January 2025. Retrieved 17 February 2025.
  7. 1 2 3 Haichin M (2025). "Psychedelics Drug Development Tracker". Psychedelic Alpha. Retrieved 27 September 2025.
  8. 1 2 3 "Platform". Home. 5 February 2025. Retrieved 17 February 2025. The most advanced program, SENS-01, is a highly selective fast-acting anxiolytic with less sedation and differentiated from standard of care. SENS-01 is presently in IND-enabling studies. We plan to enter the clinic in 1Q2025 for the treatment of social anxiety disorder (3rd most common psychiatric disease, affecting 8% of the US population) with an opportunity to expand into generalized anxiety disorder and depression.
  9. ↑ Newswire P (10 October 2024). "Sensorium Therapeutics Highlights Promising Data on Lead Assets Targeting Anxiety & Epilepsy at Neuroscience 2024". PR Newswire. Retrieved 17 February 2025.
  10. ↑ Gradisch R, Schlögl K, Lazzarin E, Niello M, Maier J, Mayer FP, et al. (January 2024). "Ligand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors". Nat Commun. 15 (1) 417. Bibcode:2024NatCo..15..417G. doi:10.1038/s41467-023-44637-6. PMC 10776687. PMID 38195746.
  11. ↑ Jacobs MT, Zhang YW, Campbell SD, Rudnick G (October 2007). "Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter". J Biol Chem. 282 (40): 29441–29447. doi:10.1074/jbc.M704456200. PMID 17698848.
  12. ↑ Coleman JA, Yang D, Zhao Z, Wen PC, Yoshioka C, Tajkhorshid E, et al. (May 2019). "Serotonin transporter-ibogaine complexes illuminate mechanisms of inhibition and transport". Nature. 569 (7754): 141–145. Bibcode:2019Natur.569..141C. doi:10.1038/s41586-019-1135-1. PMC 6750207. PMID 31019304.
  13. ↑ Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, et al. (May 2012). "The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters". J Biol Chem. 287 (22): 18524–18534. doi:10.1074/jbc.M112.343681. PMC 3365767. PMID 22451652.
  14. 1 2 Olatunji TL, Siebert F, Adetunji AE, Harvey BH, Gericke J, Hamman JH, et al. (November 2021). "Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological and clinical activities". Journal of Ethnopharmacology. 280 114476. doi:10.1016/j.jep.2021.114476. PMID 34333104.
  15. ↑ "Therapeutic alkaloid compounds". Google Patents. 8 November 2024. Retrieved 27 September 2025.
  16. ↑ "Sensorium Therapeutics to advance lead anxiety program into clinic". BioWorld. 26 September 2025. Retrieved 27 September 2025.
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