L-655708 (FG-8094) is a novel and potent nootropic agent that acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor (Ki=0.45 nM). A radiolabelled form of L-655708 was used to map the distribution of the GABAA α5 subtype in the brain. L-655708 was indeed found to produce improved cognitive performance in animal studies, without producing the side effect of convulsions which is produced by non-selective inverse agonists like DMCM.
Physicochemical Properties
| Molecular Formula | C18H19N3O4 |
| Molecular Weight | 327.33458 |
| Exact Mass | 341.138 |
| CAS # | 130477-52-0 |
| PubChem CID | 5311203 |
| Appearance | White to yellow solid powder |
| Density | 1.42g/cm3 |
| Boiling Point | 584.4ºC at 760mmHg |
| Flash Point | 307.2ºC |
| Vapour Pressure | 1.21E-13mmHg at 25°C |
| Index of Refraction | 1.675 |
| LogP | 2.286 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 25 |
| Complexity | 542 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CCOC(=O)C1=C2[C@@H]3CCCN3C(=O)C4=C(N2C=N1)C=CC(=C4)OC |
| InChi Key | YKYOQIXTECBVBB-AWEZNQCLSA-N |
| InChi Code | InChI=1S/C18H19N3O4/c1-3-25-18(23)15-16-14-5-4-8-20(14)17(22)12-9-11(24-2)6-7-13(12)21(16)10-19-15/h6-7,9-10,14H,3-5,8H2,1-2H3/t14-/m0/s1 |
| Chemical Name | ethyl (13aS)-7-methoxy-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate |
| Synonyms | L-655708 L655708 FG-8094L 655708 FG 8094L-655,708 L655,708 L 655,708 FG8094. |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | L655708, with a Ki of 0.45 nM, is a strong and specific inverse agonist of the GABAA receptor's α5 subunit-containing benzodiazepine site. Compared to GABAA receptors with α1, α2, α3, or α6 subunits and a combination of β3 and γ2, selectivity is 50–100 times better. enhances spatial learning and improves LTP in a slice model of the rat hippocampus without exhibiting proconvulsant activity. |
| ln Vivo | L-655708, administered intraperitoneally at 0.7 mg/kg, it causes modest binding to GABAA receptors containing α1, α2, and α3 subunits, 60–70% occupancy of α5 GABAA receptors, and no discernible behavioral off-target effects. Dizziness and mobility impairments are two examples. |
| References |
[1]. Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptorinverse agonist L-655708. Anesthesiology. 2010 Nov;113(5):1061-1071. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~10 mg/mL (~29.29 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.93 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1 mg/mL (2.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0550 mL | 15.2751 mL | 30.5502 mL | |
| 5 mM | 0.6110 mL | 3.0550 mL | 6.1100 mL | |
| 10 mM | 0.3055 mL | 1.5275 mL | 3.0550 mL |