| Clinical data | |
|---|---|
| Other names | SNTX2643; SENS-01; SENS01 |
| Routes of administration | Oral [1] |
| Drug class | Atypical serotonin reuptake inhibitor [1] |
| ATC code |
|
| Pharmacokinetic data | |
| Onset of action | Rapid [1] [2] |
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. [3] [4] [5] [1] [6] It is described as a novel/first-in-class and fast-acting anxiolytic without sedation. [1] [7] [2] [6] The drug is administered orally. [1]
SNTX-2643 acts as a selective atypical serotonin reuptake inhibitor. [1] [2] [6] 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] Sceletium tortuosum (kanna) acts similarly to SNTX-2643 via its primary alkaloid constituent, mesembrine, [8] but SNTX-2643 is a synthetic derivative with improved drug-like properties. [1] Unlike SSRIs, which typically require 4–6 weeks of administration to achieve therapeutic benefits, kanna is reported to have a rapid calming effect within 30–60 minutes of ingestion. [1] [2] [8] The precise mechanism underlying these differences remains unclear but appears to involve distinct downstream kinase-mediated signaling pathways. [1]
SNTX-2643 is being developed by Sensorium Therapeutics. [3] [4] [1] As of August 2025, it is undergoing phase 1 clinical trials. [1] [2] [9] Although listed on Psychedelic Alpha’s drug development tracker, SNTX-2643 is not itself a psychedelic. Its inclusion reflects its action on the serotonin system rather than any psychedelic effects. [1] [5] The chemical structure of SNTX-2643 has not yet been publicly disclosed. [3] However, mesembrine analogues acting on SERT with enhanced drug-like properties were patented by Sensorium Therapeutics in 2025. [10]
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.
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."
The most advanced program, SENS-01, is a highly selective fast-acting anxiolytic without 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.