GAT229
Positive allosteric modulator of CB1, a laboratory reagent studied on cells and in mice.
Harm-reduction warning
No characterised human dose: animal / in vitro data only. Effect profile, safety margin and acute toxicity are not documented in human clinical practice. Extremely potent compound: severe effects, seizures and deaths reported in the literature.
C₂₂H₁₈N₂O₂
CAS 889860-85-9
- Family
- ECS pharmacological toolAllosteric modulator
- Molar mass
- 342.40 g/mol
Updated on
In plain terms
GAT229 is not a hemp molecule: it is a compound made in the laboratory and used by researchers. It does not stimulate the CB1 receptor the way THC does; it acts at another site on the receptor and makes it more sensitive to the cannabinoids already present. The data cited come from studies on cells and in mice.
Receptors and activity
Target network
- Activates
The lower the cited value, the closer the target sits to GAT229: one ring per factor of 100. A target with no measured value stays on the edge.
Where these targets live
Where each target has been found in humans, according to the cited studies. The map shows the target, not an effect of GAT229.
CB1CB1 found in 7 regions of the body
- Basal gangliadenseMost dense in basal ganglia outflow nuclei1
- CerebellumdenseVery dense in the cerebellum1
- HippocampusdenseVery high concentrations in the hippocampus2
- AmygdaladenseHigh concentrations in the amygdala2
- CortexpresentPresent throughout the neocortex2
- Adipose tissuepresentExpressed in adipose tissue3
- GutpresentColonic epithelium, smooth muscle and plexus4
Map sources
- Herkenham M et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A, 1990 (new tab)
- Glass M et al. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience, 1997 (new tab)
- Engeli S et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005 (new tab)
- Wright K et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 2005 (new tab)
Cited values
- CB1Positive allosteric modulatorEC50 = 359 nM · human41 out of 100
Laprairie et al., ACS Chem Neurosci 2017 (new tab) · potentiation of [3H]CP55,940 binding, membranes of CHO cells expressing human CB1, Emax 175.5%
- CB1 (allosteric agonism)Agonistno measured value cited
Pharmacology
GAT229 is the (S) enantiomer of the racemic 2-phenylindole GAT211. It behaves as a positive allosteric modulator of CB1, with no intrinsic activity in the assays of Laprairie et al. (2017), where it increases [3H]CP55,940 binding (EC50 of 358.5 nM at human CB1) and the effect of orthosteric agonists; a residual allosteric agonism was nevertheless seen in a G protein dissociation assay (Green et al. 2024). In autaptic hippocampal neurons, it behaves as a PAM of depolarisation-induced suppression of excitation, which is mediated by 2-AG, whereas GAT228 directly activates CB1 (Mitjavila et al. 2018). In normotensive mice, GAT229 alone (0.2 or 2% topical) did not lower intraocular pressure, but combined with a sub-threshold dose of WIN 55,212-2 or THC it did; in hypertensive (nee) mice, GAT229 alone (0.2% topical or 10 mg/kg) lowered it (Cairns et al. 2017). In a corneal pain model, GAT229 alone did not reduce pain scores, but 0.5% GAT229 combined with sub-threshold Δ8-THC (0.4%) did, an effect blocked by AM251 and unchanged in CB2-deficient mice (Thapa et al. 2020). In a cisplatin neuropathy model (3 mg/kg/day for 28 days, intraperitoneally), it attenuated and slowed the onset of thermal hyperalgesia and mechanical allodynia, effects blocked by AM251 (Bagher et al. 2023). All these data are preclinical.
Key sources.
- Laprairie RB et al., Enantiospecific Allosteric Modulation of Cannabinoid 1 Receptor, ACS Chem Neurosci 2017;8(6):1188-1203 (new tab)PMID 28103441
- Mitjavila J et al., Enantiomer-specific positive allosteric modulation of CB1 signaling in autaptic hippocampal neurons, Pharmacol Res 2018 (new tab)PMID 29158048
- Cairns EA et al., The In Vivo Effects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice, J Ocul Pharmacol Ther 2017;33(8):582-590 (new tab)PMID 28719234
- Thapa D et al., Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation, Molecules 2020;25(2):417 (new tab)PMID 31968549
- Bagher AM et al., Cannabinoid receptor 1 positive allosteric modulator (GAT229) attenuates cisplatin-induced neuropathic pain in mice, Saudi Pharm J 2023;31(2):255-264 (new tab)PMID 36942271
- Green HM et al., Determination of the Cannabinoid CB1 Receptor's Positive Allosteric Modulator Binding Site through Mutagenesis Studies, Pharmaceuticals 2024;17(2):154 (new tab)PMID 38399369
- ANSM, Consolidated list of substances classified as narcotics, updated 16 February 2026, annex IV (new tab)
- PubChem, Compound Summary CID 716590 (GAT229) (new tab)
History
- Source
- A synthetic molecule of the 2-phenylindole class, the (S) enantiomer of GAT211, absent from cannabis and from any living organism. A research reagent used on cells and in rodents.
Origin
Research tool
No biosynthetic pathway: a synthetic molecule of the 2-phenylindole class, unrelated to the terpenophenolic pathway of hemp cannabinoids.
Legal framework
- European Union
A laboratory reagent; no European Union classification specific to the molecule was found in the sources consulted. Its status depends on the national law of each Member State.
- France
Not classified: absent from the ANSM list of narcotics (consolidated version updated 16/02/2026). A 2-phenylindole carrying a 2-nitro-1-phenylethyl group at position 3, with no ketone bridge or carboxamide or carboxylate function, it falls under none of the generic entries of Annex IV. The absence of classification is not a marketing authorisation.
Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.
Classification
Family, origin and source verification
- Family
ECS pharmacological tool › Allosteric modulator
- Verification
Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.
- Wikipedia (English)
No dedicated article.
References
- Laprairie RB et al., Enantiospecific Allosteric Modulation of Cannabinoid 1 Receptor, ACS Chem Neurosci 2017;8(6):1188-1203 (new tab)PMID 28103441
- Mitjavila J et al., Enantiomer-specific positive allosteric modulation of CB1 signaling in autaptic hippocampal neurons, Pharmacol Res 2018 (new tab)PMID 29158048
- Cairns EA et al., The In Vivo Effects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice, J Ocul Pharmacol Ther 2017;33(8):582-590 (new tab)PMID 28719234
- Thapa D et al., Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation, Molecules 2020;25(2):417 (new tab)PMID 31968549
- Bagher AM et al., Cannabinoid receptor 1 positive allosteric modulator (GAT229) attenuates cisplatin-induced neuropathic pain in mice, Saudi Pharm J 2023;31(2):255-264 (new tab)PMID 36942271
- Green HM et al., Determination of the Cannabinoid CB1 Receptor's Positive Allosteric Modulator Binding Site through Mutagenesis Studies, Pharmaceuticals 2024;17(2):154 (new tab)PMID 38399369
- ANSM, Consolidated list of substances classified as narcotics, updated 16 February 2026, annex IV (new tab)
- PubChem, Compound Summary CID 716590 (GAT229) (new tab)
Identifiers
Names
- IUPAC name
- 3-[(1S)-2-nitro-1-phenylethyl]-2-phenyl-1H-indole
- Other names
- GAT-229 · (S)-GAT211 · (S)-(-)-GAT211
Identifiers
- Formula
- C₂₂H₁₈N₂O₂
- CAS
- 889860-85-9
- PubChem CID
- 716590(new tab)
- InChIKey
- OHZDCJJHWPHZJD-IBGZPJMESA-N
- SMILES
- C1=
CC= C(C= C1) C2= C(C3= CC= CC= C3N2) [C@@H] (C[N+] (= O) [O-] ) C4= CC= CC= C4
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.