High‑purity Basmisanil powder CAS 1159600‑41‑5 RG1662 selective GABAA‑α5 negative allosteric modulator biochemical raw material

Basmisanil RG1662 RO5186582 CAS 1159600‑41‑5 High‑Purity Powder GABAA‑α5 Negative Allosteric Modulator Neuropharmacology Reagent

High‑purity Basmisanil powder CAS 1159600‑41‑2, also known as RG1662 and RO5186582, is an ultra‑selective negative allosteric modulator and inverse‑agonist targeting GABAA‑α5‑subtype receptor. This off‑white crystalline small‑molecule compound owns over 90‑fold receptor‑subtype selectivity against α1, α2 and α3‑GABAA receptors. It suppresses excessive inhibitory neurotransmission inside hippocampus, improves synaptic‑plasticity, rescues learning‑memory deficits and boosts cognitive performance. Widely used for laboratory research on Down‑syndrome‑related intellectual‑deficiency, schizophrenia‑associated cognitive‑impairment, memory‑deficit mechanism and fast‑onset‑antidepressant pre‑clinical tests. Every‑batch completes strict HPLC purity inspection, bulk‑order service and customizable‑packaging are available for global central‑nervous‑system pharmacology‑research clients.

Category: Tags: , , , , , ,
Basmisanil 99% Powder (CAS 1159600-41-5) | GABA-A α5 Negative Allosteric Modulator, RG1662 / RO5186582

Basmisanil 99% Powder CAS 1159600-41-5
Selective GABAA α5 Negative Allosteric Modulator

Basmisanil (RG1662 / RO5186582) is the most subtype-selective α5-GABAA negative allosteric modulator described to date — approximately 5 nM binding affinity at the human α5 subunit with more than 90-fold selectivity over α1, α2 and α3 containing receptors. By selectively lifting extrasynaptic tonic inhibition in the hippocampus it enhances learning and memory without the sedation, anxiolysis or myorelaxation of broad-spectrum benzodiazepine-site drugs. Advanced by Roche into Phase II for Down syndrome and cognitive impairment associated with schizophrenia.

GABAA α5-NAM Cognitive Enhancer ≥99% HPLC Subtype Selective Down Syndrome Research Schizophrenia Cognition Non-Sedating
Request a Quote Technical Specs
445.47
MW (C21H20FN3O5S)
~5 nM
Affinity at GABAA α5
≥99%
Purity (HPLC)

Molecular Information

Name: Basmisanil
CAS: 1159600-41-5
Formula: C21H20FN3O5S
MW: 445.47 g/mol
Purity: ≥99% (HPLC)
SMILES: CC1=C(C(=NO1)
  C2=CC=C(C=C2)F)COC3=
  NC=C(C=C3)C(=O)N4CC
  S(=O)(=O)CC4
InChIKey: VCGRFBXVSFAGGA
  -UHFFFAOYSA-N
Appearance: White to off-white powder
Solubility: DMSO (≥32 mg/mL)
Codes: RG1662 / RO5186582
Storage: -20°C, sealed, desiccated
🧪
CAS Number
1159600-41-5
⚖️
Molecular Weight
445.47
🎯
Primary Target
GABAA α5
✅
Purity
≥99%

Basmisanil Technical Specifications & QC Parameters

Complete physicochemical data and quality-control profile for research-grade Basmisanil 99% powder (CAS 1159600-41-5)

📋 Physicochemical Properties

  • Product NameBasmisanil
  • IUPAC Name(1,1-Dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone
  • CAS Number1159600-41-5
  • Development CodesRG1662 / RO5186582
  • Molecular FormulaC21H20FN3O5S
  • Molecular Weight445.47 g/mol
  • SMILESCC1=C(C(=NO1)C2=CC=C(C=C2)F)COC3=NC=C(C=C3)C(=O)N4CCS(=O)(=O)CC4
  • InChIKeyVCGRFBXVSFAGGA-UHFFFAOYSA-N
  • AppearanceWhite to off-white powder
  • Chemical ClassIsoxazolyl-methoxy-pyridine sulfone amide
  • PubChem CID57336276
  • UNII788PET5SUA
  • KEGG DrugD10863
  • ChEMBL IDCHEMBL3681419

🔬 Quality Control & Handling

  • Purity (HPLC)≥99%
  • FormCrystalline powder
  • Receptor Affinity≈5 nM at recombinant human GABAA α5
  • Subtype Selectivity>90-fold over α1, α2 and α3 subtypes
  • Functional ProfileNegative allosteric modulator / inverse agonist
  • SolubilityDMSO ≥32 mg/mL (~72 mM); insoluble in water
  • Storage Condition-20°C, sealed, desiccated, dark
  • Stock Solution Storage-20°C to -80°C, aliquoted, avoid freeze-thaw
  • QC DocumentationCOA / HPLC / NMR / MS / MSDS
  • Pack Sizes1g / 5g / 10g / 100g / 1KG
  • Stock StatusIn Stock
  • Use StatementResearch use only; not for human or clinical use

Receptor Target Profile & Subtype Selectivity

Basmisanil engages the benzodiazepine-site pocket only when the α5 subunit is present, leaving the α1, α2 and α3 subtypes that drive sedation, anxiolysis and muscle relaxation essentially untouched

🎯 GABAA α5 Subunit (GABRA5) 🧠 Hippocampal Extrasynaptic Receptors 🔇 Tonic Chloride Conductance 🚫 α1 (>90-fold selective) 🚫 α2 (>90-fold selective) 🚫 α3 (>90-fold selective) 🔗 Benzodiazepine Allosteric Site 📈 Hippocampal LTP Threshold 🧬 α5β3γ2 Pentamer 📊 [11C]Ro15-4513 PET Occupancy

Basmisanil Mechanism of Action: Selective α5 Disinhibition

How a subtype-selective negative allosteric modulator converts reduced hippocampal tonic inhibition into measurable cognitive gain — without sedation

1

α5-Restricted Binding

Basmisanil occupies the benzodiazepine allosteric site at the α/γ2 interface, but its binding energy depends on α5-specific residues. Affinity is ≈5 nM at α5β3γ2 pentamers and more than 90-fold weaker at α1, α2 and α3 assemblies.

2

Negative Allosteric Modulation

Unlike a channel blocker, it does not occlude the pore. Instead it shifts the GABA concentration-response curve to the right, reducing the chloride current evoked by a given GABA concentration only at α5-containing receptors.

3

Reduced Hippocampal Tonic Inhibition

α5-GABAA receptors sit extrasynaptically on CA1 and CA3 pyramidal neurons, where they generate a persistent tonic conductance driven by ambient GABA. Damping this leak current depolarises the effective resting state of the network.

4

Lowered LTP Threshold

With less tonic shunting, NMDA-receptor-dependent long-term potentiation is induced by weaker stimulation. Signal-to-noise across hippocampal circuits improves, which is the electrophysiological correlate of enhanced encoding.

5

Cognition Without Sedation

Because α1-mediated sedation, α2/α3-mediated anxiolysis and myorelaxation are untouched, and because inhibition is only partially reduced rather than abolished, the proconvulsant and anxiogenic liabilities of non-selective inverse agonists are avoided.

6

Translational Target Engagement

Receptor occupancy can be tracked non-invasively with the α5-preferring PET ligand [11C]Ro15-4513, and pharmaco-EEG signatures confirm central engagement — enabling a clean plasma-exposure to occupancy relationship from rodent to human.

Research Applications of the α5-GABAA NAM Basmisanil

A best-in-class chemical probe for dissecting GABAA receptor subtype pharmacology and the neurobiology of cognition

🧩

Cognitive Impairment in Down Syndrome

Trisomy 21 models such as Ts65Dn show excessive GABAergic inhibition that suppresses hippocampal plasticity. α5-selective negative allosteric modulators restore LTP and rescue spatial learning in these mice, and Basmisanil was the clinical embodiment of that hypothesis in the Phase II CLEMATIS programme.

Down Syndrome
🧠

Cognitive Impairment Associated with Schizophrenia

Post-mortem and imaging studies implicate altered hippocampal GABAergic tone in the working-memory and episodic-memory deficits of schizophrenia. Basmisanil was tested in patients on stable antipsychotics as a pro-cognitive add-on, and remains a reference tool for CIAS mechanism studies.

CIAS Research
📚

Learning, Memory & Cognition Enhancement

Used to probe hippocampus-dependent tasks — Morris water maze, novel object recognition, delayed matching-to-sample and trace conditioning — and to reverse pharmacologically induced amnesia such as diazepam-induced spatial learning impairment.

Nootropic Pharmacology
🔬

GABAA Receptor Subtype Pharmacology

An essential selectivity benchmark in recombinant α1/α2/α3/α5 β3γ2 electrophysiology panels and radioligand binding assays. Its exceptionally wide selectivity window makes it the cleanest available pharmacological substitute for α5 genetic deletion.

Receptor Pharmacology
💊

Benzodiazepine-Site Mechanism Studies

Because it binds the same allosteric pocket as diazepam but with opposite efficacy and strict subtype restriction, Basmisanil is used to deconstruct which behavioural components of benzodiazepine pharmacology arise from which receptor subtype.

Allosteric Modulation
⚡

Hippocampal Tonic Inhibition & LTP

A standard reagent in slice electrophysiology for isolating the α5-dependent component of tonic GABA current, quantifying its contribution to the LTP induction threshold, and testing excitation-inhibition balance hypotheses.

Electrophysiology
🩻

PET Imaging & Target Occupancy

Paired with [11C]Ro15-4513 or related α5-preferring radiotracers to build plasma-concentration versus receptor-occupancy curves, validate CNS penetration and set translational dose ranges for α5-directed compounds.

Translational Imaging
🛌

Post-Anaesthetic & Post-Ischaemic Memory Deficit

Excess α5-mediated tonic inhibition has been implicated in memory impairment after general anaesthesia, inflammation and stroke. α5-NAMs are used to test whether normalising tonic inhibition restores memory performance in these models.

Recovery Neuroscience
🧓

Ageing, Alzheimer's & Neurodevelopmental Disorders

Applied in models of age-related cognitive decline, amyloid-associated hippocampal hyperinhibition, autism spectrum and intellectual disability, where excitation-inhibition imbalance is a leading mechanistic hypothesis.

CNS Disease Models

Key Publications on Basmisanil & α5-GABAA Negative Allosteric Modulation

Preclinical characterisation, translational target engagement and the α5 cognition hypothesis

Hipp JF, Knoflach F, Comley R, et al. Basmisanil, a highly selective GABAA-α5 negative allosteric modulator: preclinical pharmacology and demonstration of functional target engagement in man. Scientific Reports. 2021;11:7700. [Definitive characterisation paper]
doi: 10.1038/s41598-021-87307-7
Ballard TM, Knoflach F, Prinssen E, et al. RO4938581, a novel cognitive enhancer acting at GABAA α5 subunit-containing receptors. Psychopharmacology. 2009;202(1-3):207-223. [Roche α5-NAM precursor programme]
doi: 10.1007/s00213-008-1357-7
Braudeau J, Delatour B, Duchon A, et al. Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice. Journal of Psychopharmacology. 2011;25(8):1030-1042.
doi: 10.1177/0269881111405366
Martínez-Cué C, Martínez P, Rueda N, et al. Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of Down syndrome. Journal of Neuroscience. 2013;33(9):3953-3966.
doi: 10.1523/JNEUROSCI.1203-12.2013
Dawson GR, Maubach KA, Collinson N, et al. An inverse agonist selective for α5 subunit-containing GABAA receptors enhances cognition. Journal of Pharmacology and Experimental Therapeutics. 2006;316(3):1335-1345.
doi: 10.1124/jpet.105.092320
Duchon A, Gruart A, Albac C, et al. Long-lasting correction of in vivo LTP and cognitive deficits of mice modelling Down syndrome with an α5-selective GABAA inverse agonist. British Journal of Pharmacology. 2020;177(5):1106-1118.
doi: 10.1111/bph.14903

Basmisanil 99% Powder — Pack Sizes & Ordering

Research-grade Basmisanil (CAS 1159600-41-5) supplied with full QC documentation — available in 1g / 5g / 10g / 100g / 1KG

TierPack SizeStock StatusTypical Use CaseShipping Notes
Standard1 gIn StockRadioligand binding, recombinant receptor electrophysiology, selectivity panelsSame/next-day dispatch; amber vial with desiccant
Medium5 gIn StockRodent behavioural cohorts, dose-ranging cognition studiesSame/next-day dispatch; ambient shipping, sealed foil pouch
Large10 gIn StockChronic dosing studies, PET occupancy work, multi-site collaborations1-2 business days; double-sealed, light-protected
Bulk100 gIn StockFormulation and PK/PD development, large preclinical programmesQuote to confirm; HDPE container, cool-chain option available
Industrial1 KGMade to orderPilot-scale synthesis, CRO/CMO supply contracts, repeat-supply agreementsBatch delivery on campaign schedule; per-lot COA and export documents

💡 Reference pack sizes shown above; for current pricing, lot availability and bulk Basmisanil 99% quotations please contact us for a quote. Tiered discounts apply to 100 g and 1 KG orders.

Basmisanil Frequently Asked Questions (FAQ)

What is Basmisanil (CAS 1159600-41-5)?
Basmisanil, development codes RG1662 and RO5186582, is a Roche-originated small molecule that acts as a highly selective negative allosteric modulator (inverse agonist) at GABAA receptors containing the α5 subunit. Its molecular formula is C21H20FN3O5S with a molecular weight of 445.47 g/mol. It binds recombinant human α5-GABAA receptors with approximately 5 nM affinity and displays greater than 90-fold selectivity over α1, α2 and α3 containing receptors — the widest α5 selectivity window reported for any characterised compound in this class.
How is an α5-NAM different from a benzodiazepine?
Two differences matter: direction and subtype scope. Diazepam and other classical benzodiazepines are positive allosteric modulators acting across α1, α2, α3 and α5 subtypes, which is why they sedate, relieve anxiety, relax muscle and impair memory. Basmisanil is a negative allosteric modulator that acts essentially only at α5. It therefore reduces — rather than enhances — inhibitory current, and does so only in the hippocampus-enriched α5 population. The result is a pro-cognitive rather than amnestic profile, with no benzodiazepine-type sedation.
Why does reducing α5 GABAA tone improve cognition instead of causing seizures?
Because the reduction is both partial and subtype-restricted. α5 receptors are largely extrasynaptic and contribute a persistent tonic conductance that raises the threshold for LTP; damping that leak improves signal-to-noise for encoding. Meanwhile the phasic, synaptic inhibition mediated by α1, α2 and α3 receptors that keeps cortical and hippocampal networks from runaway excitation is completely preserved. Non-selective inverse agonists such as FG-7142 removed all of that protection, which is why they were anxiogenic and proconvulsant; α5 selectivity is precisely what removed that liability.
What was the clinical development status of Basmisanil?
Roche advanced Basmisanil to Phase II. The CLEMATIS study assessed it for intellectual disability associated with Down syndrome in adolescents and adults across multiple countries; in 2016 Roche reported that the programme did not meet its cognitive endpoints and discontinued development for that indication. A separate Phase II study (NCT02953639) evaluated cognitive impairment associated with schizophrenia in patients receiving antipsychotics. Basmisanil is not an approved medicine and is supplied here strictly as a laboratory research reagent.
Which α5-GABAA assays is Basmisanil suitable for?
It performs well as a reference antagonist/NAM in: recombinant two-electrode voltage clamp or whole-cell patch clamp on α1/α2/α3/α5 β3γ2 receptors expressed in oocytes or HEK293 cells; [3H]flumazenil or [3H]Ro15-4513 competition binding; hippocampal slice recordings of tonic GABA current and LTP threshold; and in vivo PET occupancy using α5-preferring tracers. It is also a standard positive control in behavioural cognition batteries.
How should Basmisanil be dissolved and stored?
Basmisanil is freely soluble in DMSO at ≥32 mg/mL (roughly 72 mM) and essentially insoluble in water. Prepare a concentrated DMSO stock, warm briefly and vortex if needed, aliquot, and dilute into buffer or culture medium immediately before use, keeping final DMSO ≤0.1% v/v in cell-based work. Store the solid at -20 °C, sealed, desiccated and protected from light. Store DMSO stocks at -20 °C for short-term or -80 °C for long-term use, and avoid repeated freeze-thaw cycles.
Does Basmisanil cross the blood-brain barrier?
Yes. Central target engagement was demonstrated in both rodents and humans: dose-dependent α5 receptor occupancy was measured in vivo, and pharmaco-EEG changes confirmed CNS activity in clinical studies. A well-behaved plasma-exposure to receptor-occupancy relationship was established during development, which is one reason the compound is valued as a translational tool for setting brain-penetrant dose ranges.
How does Basmisanil compare with α5IA, L-655,708, MRK-016 and RO4938581?
L-655,708 is an early, widely used α5-preferring inverse agonist but has modest selectivity and poor drug-like properties. α5IA and MRK-016 were Merck clinical candidates with better selectivity but development-limiting tolerability findings. RO4938581 was Roche's earlier α5-NAM and the direct scientific predecessor of Basmisanil. Basmisanil represents the most refined member of the series: the highest reported α5 selectivity (>90-fold), clean functional discrimination in recombinant electrophysiology, and demonstrated human target engagement.
What concentrations and controls are recommended?
In recombinant electrophysiology, functional effects are typically probed in the low nanomolar to low micromolar range with full concentration-response curves; binding assays use nanomolar concentrations around the ≈5 nM Ki. Always run (1) a vehicle-matched DMSO control; (2) a parallel α1/α2/α3 arm to confirm the selectivity window in your own hands; (3) a reference positive allosteric modulator such as diazepam to verify assay direction; and (4) where available, an α5 knockout or α5 point-mutant comparison to confirm on-target attribution.
What QC documentation is supplied with 99% Basmisanil, and are bulk quantities available?
Every lot ships with a Certificate of Analysis (COA) reporting HPLC purity (≥99%), 1H NMR structural confirmation and MS identity data. MSDS/SDS, solubility datasheets, residual-solvent data and Certificates of Origin are available on request. Pack sizes span 1 g, 5 g, 10 g, 100 g and 1 KG, with the 1 KG tier manufactured to order on a campaign basis. For custom purity specifications, alternative packaging or long-term supply agreements please contact our technical sales team.

Need Basmisanil 99% Powder for Your Cognition Research?

Research-grade Basmisanil (CAS 1159600-41-5, RG1662 / RO5186582) — purity ≥99% HPLC, COA included, 1g to 1KG
The most selective GABAA α5 negative allosteric modulator available — request your quote today

Request a Quote →

Related products