Basmisanil — Safety, Research, Risks & Legal Status

Not medical advice. Basmisanil is discussed here for informational and harm-reduction purposes only. We do not endorse use, and any dosing context is informational, not a protocol.

Also known as	RG1662, RO5186582, NTX-1511
Category	Research Chemical
Drug class	Selective GABA-A alpha-5 subunit negative allosteric modulator (NAM); inverse agonist at benzodiazepine binding site
Development codes	RG1662, RO5186582 (Roche); NTX-1511 (Newleos Therapeutics, as of 2025)
Alpha-5 binding affinity	~5 nM at human recombinant GABA-A alpha-5 receptor; >90-fold selectivity over alpha-1, alpha-2, alpha-3 subunits
Phase 2 Down syndrome trial outcome	Primary endpoint failed (p=0.262); pharmacodynamic EEG target engagement confirmed despite lack of clinical efficacy
Current ownership	Newleos Therapeutics (acquired from Roche, February 2025; $93.5M Series A); no active IND as of mid-2026
CAS number	1159600-41-5
US legal status	No FDA approval and not marketed in the US. Basmisanil was investigated under Investigational New Drug (IND) status during Roche-sponsored Phase 2 trials; all are now closed or terminated. It is not a controlled substance under the CSA. Roche discontinued development in 2024; the asset was acquired by Newleos Therapeutics (February 2025), which is a private clinical-stage company. No active IND filings or approved indication exist as of mid-2026. It is not available as a legal supplement or approved drug. Possession and use outside a clinical trial framework occupies a legal gray area as an uninvestigated unapproved drug, not for human consumption.

What is Basmisanil?

Basmisanil is a clinical-stage, small-molecule negative allosteric modulator (NAM) that selectively targets the alpha-5 subunit-containing GABA-A receptor. It was developed by Roche primarily for neurodevelopmental indications -- specifically Down syndrome and Dup15q syndrome -- based on the hypothesis that selectively reducing tonic inhibitory GABAergic tone in the hippocampus could improve cognitive function in these disorders. All Phase 2 trials have concluded without demonstrating clinical efficacy on primary endpoints. The drug failed its pivotal Down syndrome trial in 2022, the Dup15q trial was terminated early by Roche in 2024, and a schizophrenia cognitive impairment trial was also discontinued. Newleos Therapeutics acquired the compound in February 2025 and has stated intent to pursue further clinical investigation, particularly in Dup15q syndrome.

How it works

Basmisanil acts as an inverse agonist at the benzodiazepine binding site of GABA-A receptors that contain the alpha-5 subunit. Alpha-5-containing GABA-A receptors are predominantly extrasynaptic and are concentrated in the hippocampus, where they mediate tonic (persistent) inhibitory conductance rather than phasic synaptic inhibition. By acting as a NAM at this subtype, basmisanil reduces baseline inhibitory tone. The therapeutic rationale is that individuals with Down syndrome and Dup15q syndrome have excess GABAergic inhibition -- an excitation-inhibition (E/I) imbalance -- that suppresses hippocampal circuit activity underlying learning and memory. Selectively attenuating alpha-5 receptor activity is hypothesized to partially correct this imbalance without the sedation, anxiolysis, or seizure-risk profile of benzodiazepine site ligands that hit alpha-1, alpha-2, or alpha-3 subunits. Binding affinity at human recombinant GABA-A alpha-5 receptors is approximately 5 nM, with greater than 90-fold selectivity over the other major benzodiazepine-sensitive subunits (alpha-1, alpha-2, alpha-3). Pharmacodynamic target engagement was confirmed in the Down syndrome Clematis trial via EEG: basmisanil produced significant increases in theta power (~9%, effect size d=0.94) and decreases in beta power (~13%, d=-1.04) relative to placebo, indicating the drug reached its biological target in the brain despite failing to produce clinical benefit.

Background & history

Basmisanil (development codes RG1662, RO5186582) was discovered and developed by F. Hoffmann-La Roche. Preclinical pharmacology established its selectivity profile and mechanistic rationale in vitro and in animal models. Phase 2 clinical trials were conducted across three indications: Down syndrome (Clematis trial, NCT02024789; enrolled 2014-2021), cognitive impairment associated with schizophrenia (CIAS; NCT02953639; conducted 2016-2019), and Dup15q syndrome (Quindecim trial, NCT05307679). The Clematis Down syndrome trial -- 170 enrolled participants ages 12-30, randomized double-blind placebo-controlled, 6 months of treatment -- reported results in 2022 showing failure of the primary composite endpoint of cognitive and adaptive behavior improvement (29% placebo responders vs. 20-25% basmisanil; p=0.262), with no significant secondary endpoint differences. The schizophrenia CIAS indication was also discontinued without reported success. The Dup15q trial was prematurely terminated by Roche in 2024 before collecting efficacy data. In February 2025, Newleos Therapeutics, a newly formed private biotech backed by Goldman Sachs Alternatives, Novo Holdings, Longwood Fund, DCVC Bio, and Arkin Bio Capital, announced a $93.5 million Series A and acquisition of four former Roche neurodevelopmental assets including basmisanil, now designated NTX-1511. Newleos has indicated intent to pursue Dup15q as a development path, but no active IND filings had been publicly announced as of mid-2026.

What the research says

Human evidence is limited to three Phase 2 trials, all of which failed primary endpoints or were terminated early. The Clematis trial (Down syndrome; n=170, randomized double-blind placebo-controlled, 6 months) is the most complete dataset: it failed its primary composite endpoint of cognitive plus adaptive functioning improvement (p=0.262). No significant differences were observed on any secondary measures including the RBANS cognitive battery, VABS-II adaptive behavior scale, CELF-4 language assessment, or BRIEF-P executive function rating. Critically, pharmacodynamic EEG data confirmed target engagement, meaning drug reached the brain and modulated its intended receptor, yet did not translate to functional clinical improvement. The CIAS (schizophrenia cognitive impairment) Phase 2 trial conducted 2016-2019 was not reported as successful and was discontinued. The Dup15q Phase 2 trial (NCT05307679; 52-week design) was prematurely terminated by Roche in 2024 before meaningful efficacy data were collected. Preclinical data (animal and in vitro) establish mechanistic plausibility: basmisanil inhibits tonic inhibitory conductance in mouse hippocampal neurons and shows high selectivity in receptor binding assays. Proposed explanations for the clinical gap include high placebo response rates in pediatric neurodevelopmental trials (10-30%), caregiver-expectancy bias in adaptive behavior outcome measures, potential inadequacy of the E/I imbalance hypothesis as a therapeutic lever in the post-developmental period, and the possibility that intervention may need to occur at younger developmental ages. No published peer-reviewed evidence supports cognitive enhancement in healthy or typical adult humans. No human evidence exists for any nootropic or performance-enhancement application. In summary: preclinical rationale established; Phase 2 human trials completed; primary endpoints failed; compound currently in limbo pending Newleos development plans.

Reported effects

Pharmacodynamic target engagement confirmed: EEG theta power increase (~9%) and beta power decrease (~13%) in Down syndrome trial versus placebo, indicating CNS penetration and receptor modulation
No statistically significant improvement in composite cognitive or adaptive functioning endpoints in Phase 2 Down syndrome trial (primary endpoint failed, p=0.262)
No significant effects on RBANS cognition, VABS-II adaptive behavior, CELF-4 language, or BRIEF-P executive function in Down syndrome trial
Mechanism hypothesizes reduction of excess tonic GABAergic inhibition in hippocampus, theorized to disinhibit cognitive circuits - but this did not produce measurable clinical benefit in completed trials
No demonstrated effects in schizophrenia CIAS indication (Phase 2 discontinued)
No human data exist on effects in healthy individuals or typical adults - any effects in this population are entirely unknown

Dosing & administration (informational)

In the Clematis Phase 2 Down syndrome trial, doses studied were 120 mg and 240 mg twice daily (BID) for adults, with 80 mg and 160 mg BID for participants ages 12-13. These are investigational doses reported in peer-reviewed literature for informational and reference purposes only. They do not represent a recommended protocol and cannot be extrapolated to other populations, indications, or contexts. Appropriate dosing for any individual requires evaluation by a qualified clinician, which is not possible outside a properly authorized clinical trial. No dosing guidance for off-label or self-administration use can be offered.

This is general research/context information, not medical advice or a recommended protocol.

Safety & side effects

Favorable safety profile observed in Phase 2 trials: adverse event frequency and character were similar between basmisanil and placebo arms
Serious adverse events (n=5 in Clematis Down syndrome trial) were all judged unrelated to study drug
Withdrawals due to adverse events were low (n=4): reasons included headache/nausea/vomiting, sleep apnea, nightmares, and altered consciousness; no placebo withdrawals for AEs
No treatment-emergent seizures or epileptiform EEG abnormalities observed in trials
No safety signals in healthy volunteer PET and EEG pharmacodynamic studies
Long-term safety in humans beyond 6-month trial duration is not established
Safety in healthy adults or for off-label/non-clinical-trial use is entirely unknown - no data exist for this context

Drug & supplement interactions

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Who should avoid it

Concurrent use with benzodiazepines, barbiturates, or other positive allosteric modulators of GABA-A receptors - mechanistic opposition or complex interaction
Use in individuals with epilepsy or personal/family history of seizures outside medical supervision
Use in pregnant or breastfeeding individuals - no safety data
Use in children outside a supervised clinical trial - developmental safety data do not exist beyond the specific trial populations studied
Any self-administration or off-label use - compound has no approved indication and gray-market sourcing cannot be verified
Combining with alcohol - both affect GABAergic tone; interaction profile unknown

How it is commonly combined

No evidence base exists for combining basmisanil with other compounds for any purpose. The drug has not been studied in combination regimens. Any speculation about stacking with other cognitive agents, nootropics, or pharmaceuticals would be unsupported by clinical data and potentially unsafe.

Legal & regulatory. No FDA approval and not marketed in the US. Basmisanil was investigated under Investigational New Drug (IND) status during Roche-sponsored Phase 2 trials; all are now closed or terminated. It is not a controlled substance under the CSA. Roche discontinued development in 2024; the asset was acquired by Newleos Therapeutics (February 2025), which is a private clinical-stage company. No active IND filings or approved indication exist as of mid-2026. It is not available as a legal supplement or approved drug. Possession and use outside a clinical trial framework occupies a legal gray area as an uninvestigated unapproved drug, not for human consumption.

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Frequently asked questions

What is basmisanil supposed to do?

Basmisanil was designed to reduce excess tonic inhibitory signaling in the hippocampus by blocking a specific subtype of GABA-A receptor (alpha-5 containing). The hypothesis was that this could partially correct an excitation-inhibition imbalance in neurodevelopmental conditions like Down syndrome and Dup15q syndrome, potentially improving learning and memory. Despite confirmed pharmacodynamic target engagement, Phase 2 trials did not show clinical benefit on primary endpoints.

Did basmisanil work in clinical trials?

No. The most complete trial - the Clematis Phase 2 study in Down syndrome (n=170, 6 months, double-blind placebo-controlled) - failed its primary endpoint and showed no significant differences on any secondary measure. Interestingly, EEG data confirmed the drug reached its receptor target and produced the expected biological signal in the brain, but this did not translate to measurable improvement in cognition or adaptive functioning. The Dup15q trial was terminated early before efficacy could be assessed, and the schizophrenia CIAS trial was also discontinued.

Can basmisanil be used as a nootropic or cognitive enhancer?

There is no evidence supporting use in healthy adults or for cognitive enhancement purposes. All human data come from patients with specific neurodevelopmental disorders, and even in those populations the drug failed to demonstrate benefit. The effects in neurotypical individuals are entirely unknown. Use outside a clinical trial context has no safety or efficacy data to support it.

What is the current legal status in the US?

Basmisanil has no FDA approval and is not marketed. It is not listed as a controlled substance under the Controlled Substances Act. Its prior clinical use occurred under Investigational New Drug (IND) status, which no longer covers it now that Roche's trials are closed. It exists in a legal gray area as an unapproved investigational drug. It is not a legal supplement or food product.

What is Newleos Therapeutics and what are they doing with basmisanil?

Newleos Therapeutics is a private clinical-stage biotech formed in 2025 that acquired several neurodevelopmental assets from Roche, including basmisanil (now designated NTX-1511). The company raised $93.5 million in a Series A financing backed by Goldman Sachs Alternatives, Novo Holdings, Longwood Fund, DCVC Bio, and Arkin Bio Capital. Newleos has indicated intent to pursue further clinical development, with Dup15q syndrome as a stated target. No active IND filings had been publicly announced as of mid-2026.

What dosing was used in the clinical trials?

The Clematis Down syndrome trial used 120 mg and 240 mg twice daily (BID) in adults, and 80 mg and 160 mg BID in participants ages 12-13. These are literature reference points only and do not constitute dosing recommendations for any purpose. Appropriate dosing for any clinical use requires evaluation by a qualified physician within a properly authorized trial framework. Consult a clinician for any medical questions.

References & further reading

PubMed: basmisanil GABA-A alpha5 negative allosteric modulator RG1662 preclinical pharmacology (Witkin et al., Scientific Reports 11:7946, 2021)
PubMed: basmisanil RG1662 Down syndrome Clematis Phase 2 randomized controlled trial (Olmos-Serrano et al., Journal of Neurodevelopmental Disorders 14:13, 2022)
ClinicalTrials.gov: NCT02024789 (Clematis - Down syndrome, completed)
ClinicalTrials.gov: NCT05307679 (Quindecim - Dup15q syndrome, terminated 2024)
ClinicalTrials.gov: NCT02953639 (schizophrenia CIAS Phase 2, discontinued)