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MedKoo Cat#: 526619 | Name: L-655708
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

L-655708, also known as FG-8094, is a nootropic drug. L-655708 acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. 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.

Chemical Structure

L-655708
L-655708
CAS#130477-52-0

Theoretical Analysis

MedKoo Cat#: 526619

Name: L-655708

CAS#: 130477-52-0

Chemical Formula: C18H19N3O4

Exact Mass: 341.1376

Molecular Weight: 341.37

Elemental Analysis: C, 63.33; H, 5.61; N, 12.31; O, 18.75

Price and Availability

Size Price Availability Quantity
10mg USD 350.00 2 Weeks
50mg USD 950.00 2 Weeks
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Related CAS #
No Data
Synonym
L-655708; L655708; L 655708; L-655,708; L655,708; L 655,708; FG-8094; FG 8094; FG8094.
IUPAC/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
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
SMILES Code
O=C(C1=C([C@@]2([H])N3CCC2)N(C=N1)C4=CC=C(OC)C=C4C3=O)OCC
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
L-655708 is a potent α5 subunit-selective GABAA receptor inverse agonist (Ki=0.45 nM).
In vitro activity:
L-655,708 (50 nM) reduced sevoflurane potentiation of GABA-evoked current in wild-type neurones but not Gabra5-/- neurones, and produced a rightward shift in the sevoflurane concentration-response plot [sevoflurane EC50: 1.9 (0.1) mM; sevoflurane+L-655,708 EC(50): 2.4 (0.2) mM, P<0.05]. Similarly, L-655,708 (50 nM) reduced isoflurane potentiation of GABA-evoked current [isoflurane: 4.0 (0.6) pA pF(-1); isoflurane+L-655,708: 3.1 (0.5) pA pF(-1), P<0.01]. Reference: Br J Anaesth. 2013 Jun;110 Suppl 1(Suppl 1):i73-81. https://pubmed.ncbi.nlm.nih.gov/23535829/
In vivo activity:
Pharmacological blocking of an underlying tonically active GABA conductance using the GABA-α5 subunit inverse agonist, L-655-708, disinhibited mouse WT JC MNs (wildtype jaw closer motor neurons) and lowered their recruitment threshold, suggesting its role in the control of intrinsic MN excitability. Reference: Neurobiol Dis. 2023 Jan 6;177:105992. https://pubmed.ncbi.nlm.nih.gov/36623607/
Solvent mg/mL mM
Solubility
DMF:PBS (pH 7.2) (1:20) 0.0 0.12
DMSO 9.8 28.84
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 341.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Lecker I, Yin Y, Wang DS, Orser BA. Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by α5GABAA receptor-preferring inverse agonists. Br J Anaesth. 2013 Jun;110 Suppl 1(Suppl 1):i73-81. doi: 10.1093/bja/aet038. Epub 2013 Mar 27. PMID: 23535829; PMCID: PMC3732063. 2. Papatheodoropoulos C, Koniaris E. α5GABAA receptors regulate hippocampal sharp wave-ripple activity in vitro. Neuropharmacology. 2011 Mar;60(4):662-73. doi: 10.1016/j.neuropharm.2010.11.022. Epub 2010 Dec 10. PMID: 21146551. 3. Venugopal S, Ghulam-Jhelani Z, Ahn IS, Yang X, Wiedau M, Simmons D, Chandler SH. Early deficits in GABA inhibition parallels an increase in L-type Ca2+ currents in the jaw motor neurons of SOD1G93A mouse model for ALS. Neurobiol Dis. 2023 Jan 6;177:105992. doi: 10.1016/j.nbd.2023.105992. Epub ahead of print. PMID: 36623607. 4. Inoue T, Takamatsu Y, Nishio T, Soma K, Okamura M, Tohyama H, Maejima H. Combined treatment with exercise and α5GABAAR inhibitor promotes motor function recovery after intracerebral hemorrhage. Neurosci Lett. 2022 Jan 1;766:136344. doi: 10.1016/j.neulet.2021.136344. Epub 2021 Nov 14. PMID: 34785309.
In vitro protocol:
1. Lecker I, Yin Y, Wang DS, Orser BA. Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by α5GABAA receptor-preferring inverse agonists. Br J Anaesth. 2013 Jun;110 Suppl 1(Suppl 1):i73-81. doi: 10.1093/bja/aet038. Epub 2013 Mar 27. PMID: 23535829; PMCID: PMC3732063. 2. Papatheodoropoulos C, Koniaris E. α5GABAA receptors regulate hippocampal sharp wave-ripple activity in vitro. Neuropharmacology. 2011 Mar;60(4):662-73. doi: 10.1016/j.neuropharm.2010.11.022. Epub 2010 Dec 10. PMID: 21146551.
In vivo protocol:
1. Venugopal S, Ghulam-Jhelani Z, Ahn IS, Yang X, Wiedau M, Simmons D, Chandler SH. Early deficits in GABA inhibition parallels an increase in L-type Ca2+ currents in the jaw motor neurons of SOD1G93A mouse model for ALS. Neurobiol Dis. 2023 Jan 6;177:105992. doi: 10.1016/j.nbd.2023.105992. Epub ahead of print. PMID: 36623607. 2. Inoue T, Takamatsu Y, Nishio T, Soma K, Okamura M, Tohyama H, Maejima H. Combined treatment with exercise and α5GABAAR inhibitor promotes motor function recovery after intracerebral hemorrhage. Neurosci Lett. 2022 Jan 1;766:136344. doi: 10.1016/j.neulet.2021.136344. Epub 2021 Nov 14. PMID: 34785309.
1: Shen H, Sabaliauskas N, Yang L, Aoki C, Smith SS. Role of α4-containing GABA(A) receptors in limiting synaptic plasticity and spatial learning of female mice during the pubertal period. Brain Res. 2016 Jan 26. pii: S0006-8993(16)00033-0. doi: 10.1016/j.brainres.2016.01.020. [Epub ahead of print] PubMed PMID: 26826007. 2: Pangratz-Fuehrer S, Sieghart W, Rudolph U, Parada I, Huguenard JR. Early postnatal switch in GABAA receptor α-subunits in the reticular thalamic nucleus. J Neurophysiol. 2016 Mar 1;115(3):1183-95. doi: 10.1152/jn.00905.2015. Epub 2015 Dec 2. PubMed PMID: 26631150; PubMed Central PMCID: PMC4808120. 3: Groundwater PW, Hamid K, Ng I, Tallapragada VJ, Hibbs DE, Hanrahan J. The Differential Effects of Resveratrol and trans-ε-Viniferin on the GABA-Induced Current in GABAA Receptor Subtypes Expressed in Xenopus Laevis Oocytes. J Pharm Pharm Sci. 2015;18(4):328-38. PubMed PMID: 26626239. 4: Bravo-Hernández M, Corleto JA, Barragán-Iglesias P, González-Ramírez R, Pineda-Farias JB, Felix R, Calcutt NA, Delgado-Lezama R, Marsala M, Granados-Soto V. The α5 subunit containing GABAA receptors contribute to chronic pain. Pain. 2016 Mar;157(3):613-26. doi: 10.1097/j.pain.0000000000000410. PubMed PMID: 26545088. 5: Engin E, Zarnowska ED, Benke D, Tsvetkov E, Sigal M, Keist R, Bolshakov VY, Pearce RA, Rudolph U. Tonic Inhibitory Control of Dentate Gyrus Granule Cells by α5-Containing GABAA Receptors Reduces Memory Interference. J Neurosci. 2015 Oct 7;35(40):13698-712. doi: 10.1523/JNEUROSCI.1370-15.2015. PubMed PMID: 26446222; PubMed Central PMCID: PMC4595621. 6: Lake EM, Chaudhuri J, Thomason L, Janik R, Ganguly M, Brown M, McLaurin J, Corbett D, Stanisz GJ, Stefanovic B. The effects of delayed reduction of tonic inhibition on ischemic lesion and sensorimotor function. J Cereb Blood Flow Metab. 2015 Oct;35(10):1601-9. doi: 10.1038/jcbfm.2015.86. Epub 2015 May 13. PubMed PMID: 25966952; PubMed Central PMCID: PMC4640317. 7: Fischell J, Van Dyke AM, Kvarta MD, LeGates TA, Thompson SM. Rapid Antidepressant Action and Restoration of Excitatory Synaptic Strength After Chronic Stress by Negative Modulators of Alpha5-Containing GABAA Receptors. Neuropsychopharmacology. 2015 Oct;40(11):2499-509. doi: 10.1038/npp.2015.112. Epub 2015 Apr 22. PubMed PMID: 25900119; PubMed Central PMCID: PMC4569955. 8: Povroznik JM, Rudy CC, Hunsberger HC, Tosto DE, Reed MN. Effects of an α5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task. Behav Pharmacol. 2014 Aug;25(4):331-5. doi: 10.1097/FBP.0000000000000053. PubMed PMID: 25006978; PubMed Central PMCID: PMC4410981. 9: Pofantis H, Papatheodoropoulos C. The α5GABAA receptor modulates the induction of long-term potentiation at ventral but not dorsal CA1 hippocampal synapses. Synapse. 2014 Sep;68(9):394-401. doi: 10.1002/syn.21751. Epub 2014 May 23. PubMed PMID: 24823837. 10: Bravo-Hernández M, Feria-Morales LA, Torres-López JE, Cervantes-Durán C, Delgado-Lezama R, Granados-Soto V, Rocha-González HI. Evidence for the participation of peripheral α5 subunit-containing GABAA receptors in GABAA agonists-induced nociception in rats. Eur J Pharmacol. 2014 Jul 5;734:91-7. doi: 10.1016/j.ejphar.2014.03.051. Epub 2014 Apr 12. PubMed PMID: 24726872. 11: Pandit S, Song JG, Kim YJ, Jeong JA, Jo JY, Lee GS, Kim HW, Jeon BH, Lee JU, Park JB. Attenuated benzodiazepine-sensitive tonic GABAA currents of supraoptic magnocellular neuroendocrine cells in 24-h water-deprived rats. J Neuroendocrinol. 2014 Jan;26(1):26-34. doi: 10.1111/jne.12123. PubMed PMID: 24313753. 12: Loeza-Alcocer E, Canto-Bustos M, Aguilar J, González-Ramírez R, Felix R, Delgado-Lezama R. α(5)GABA(A) receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord. J Neurophysiol. 2013 Nov;110(9):2175-84. doi: 10.1152/jn.00330.2013. Epub 2013 Aug 21. PubMed PMID: 23966669. 13: Lecker I, Yin Y, Wang DS, Orser BA. Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by α5GABAA receptor-preferring inverse agonists. Br J Anaesth. 2013 Jun;110 Suppl 1:i73-81. doi: 10.1093/bja/aet038. Epub 2013 Mar 27. PubMed PMID: 23535829; PubMed Central PMCID: PMC3732063. 14: Drexler B, Zinser S, Huang S, Poe MM, Rudolph U, Cook JM, Antkowiak B. Enhancing the function of alpha5-subunit-containing GABAA receptors promotes action potential firing of neocortical neurons during up-states. Eur J Pharmacol. 2013 Mar 5;703(1-3):18-24. doi: 10.1016/j.ejphar.2013.01.034. Epub 2013 Feb 1. PubMed PMID: 23380687; PubMed Central PMCID: PMC3996676. 15: Rüedi-Bettschen D, Rowlett JK, Rallapalli S, Clayton T, Cook JM, Platt DM. Modulation of α5 subunit-containing GABAA receptors alters alcohol drinking by rhesus monkeys. Alcohol Clin Exp Res. 2013 Apr;37(4):624-34. doi: 10.1111/acer.12018. Epub 2012 Nov 5. PubMed PMID: 23126673; PubMed Central PMCID: PMC3951841. 16: Numata JM, van Brederode JF, Berger AJ. Lack of an endogenous GABAA receptor-mediated tonic current in hypoglossal motoneurons. J Physiol. 2012 Jul 1;590(13):2965-76. doi: 10.1113/jphysiol.2012.231944. Epub 2012 Apr 10. PubMed PMID: 22495589; PubMed Central PMCID: PMC3406384. 17: Zurek AA, Bridgwater EM, Orser BA. Inhibition of α5 γ-Aminobutyric acid type A receptors restores recognition memory after general anesthesia. Anesth Analg. 2012 Apr;114(4):845-55. doi: 10.1213/ANE.0b013e31824720da. Epub 2012 Mar 1. PubMed PMID: 22383672. 18: Castro A, Aguilar J, González-Ramírez R, Loeza-Alcocer E, Canto-Bustos M, Felix R, Delgado-Lezama R. Tonic inhibition in spinal ventral horn interneurons mediated by α5 subunit-containing GABA(A) receptors. Biochem Biophys Res Commun. 2011 Aug 19;412(1):26-31. doi: 10.1016/j.bbrc.2011.07.026. Epub 2011 Jul 21. PubMed PMID: 21798246. 19: Jo JY, Jeong JA, Pandit S, Stern JE, Lee SK, Ryu PD, Lee SY, Han SK, Cho CH, Kim HW, Jeon BH, Park JB. Neurosteroid modulation of benzodiazepine-sensitive GABAA tonic inhibition in supraoptic magnocellular neurons. Am J Physiol Regul Integr Comp Physiol. 2011 Jun;300(6):R1578-87. doi: 10.1152/ajpregu.00627.2010. Epub 2011 Mar 30. PubMed PMID: 21451144. 20: Papatheodoropoulos C, Koniaris E. α5GABAA receptors regulate hippocampal sharp wave-ripple activity in vitro. Neuropharmacology. 2011 Mar;60(4):662-73. doi: 10.1016/j.neuropharm.2010.11.022. Epub 2010 Dec 10. PubMed PMID: 21146551.

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