SKF89976A HCl | CAS#85375-15-1 | GABA uptake inhibitor

MedKoo Cat#: 556097 | Name: SKF89976A HCl

Description:

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

SKF89976A is a potent GABA uptake inhibitor, which is selective for GAT-1 (IC50 values are 0.13, 550, 944 and 7210 μM for hGAT-1, rGAT-2, hGAT-3 and hBGT-1 respectively). SKF89976A inhibits transport current competitively (Ki = 7 μM) and transmitter-gated current non-competitively (Ki = 0.03 nM). It is able to pass the blood-brain barrier after systemic administration and is active in vivo.

Chemical Structure

SKF89976A HCl

CAS#85375-15-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 556097

Name: SKF89976A HCl

CAS#: 85375-15-1 (HCl)

Chemical Formula: C22H26ClNO2

Exact Mass: 0.0000

Molecular Weight: 371.91

Elemental Analysis: C, 71.05; H, 7.05; Cl, 9.53; N, 3.77; O, 8.60

Price and Availability

Size	Price	Availability
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 1,950.00	2 Weeks
500mg	USD 2,950.00	2 Weeks
1g	USD 4,650.00	2 Weeks
2g	USD 6,950.00	2 Weeks

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Related CAS #

85375-15-1 (HCl) 85375-85-5 (free base)

Synonym

SKF89976A HCl; SKF 89976A; SKF-89976A; SKF89976A hydrochloride

IUPAC/Chemical Name

1-(4,4-diphenylbut-3-en-1-yl)piperidine-3-carboxylic acid hydrochloride

InChi Key

SNGGBKYQZVAQKA-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H25NO2.ClH/c24-22(25)20-13-7-15-23(17-20)16-8-14-21(18-9-3-1-4-10-18)19-11-5-2-6-12-19;/h1-6,9-12,14,20H,7-8,13,15-17H2,(H,24,25);1H

SMILES Code

O=C(C1CN(CC/C=C(C2=CC=CC=C2)/C3=CC=CC=C3)CCC1)O.[H]Cl

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 and water

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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:

SKF 89976A is a potent GABA uptake inhibitor, selective for GAT-1 (IC50 values are 0.13, 550, 944 and 7210 μM for hGAT-1, rGAT-2, hGAT-3 and hBGT-1 respectively). SKF 89976A inhibits transport current competitively (Ki = 7 μM) and transmitter-gated current non-competitively (Ki = 0.03 nM). SKF 89976A is able to pass the blood-brain barrier after systemic administration and is active in vivo.

In vitro activity:

To be determined

In vivo activity:

In rat cerebellar slices, whole-cell patch-clamp recordings from Bergmann glia were conducted to explore GABA transporters (GATs). Blockers of GAT-1 (SKF89976-A and NNC-711) significantly decreased GABA-induced transport currents. SKF89976-A also inhibited baseline inward currents, indicating tonic GAT activation. The results suggest that Bergmann glia express GAT-1 activated by ambient GABA, and GAT-1 can operate in reverse, releasing GABA to activate nearby receptors. Reference: J Neurophysiol. 2002 Sep;88(3):1407-19. https://pubmed.ncbi.nlm.nih.gov/12205162/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	268.89
	Water	20.0	53.78

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 371.91 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.

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. Barakat L, Bordey A. GAT-1 and reversible GABA transport in Bergmann glia in slices. J Neurophysiol. 2002 Sep;88(3):1407-19. doi: 10.1152/jn.2002.88.3.1407. PMID: 12205162. 2. Zuiderwijk M, Veenstra E, Lopes da Silva FH, Ghijsen WE. Effects of uptake carrier blockers SK & F 89976-A and L-trans-PDC on in vivo release of amino acids in rat hippocampus. Eur J Pharmacol. 1996 Jul 4;307(3):275-82. doi: 10.1016/0014-2999(96)00284-1. PMID: 8836615.

In vitro protocol:

To be determined

In vivo protocol:

1: Kinjo A, Sassa M, Koito T, Suzuki M, Inoue K. Functional characterization of the GABA transporter GAT-1 from the deep-sea mussel Bathymodiolus septemdierum. Comp Biochem Physiol A Mol Integr Physiol. 2019 Jan;227:1-7. doi: 10.1016/j.cbpa.2018.08.016. Epub 2018 Sep 6. PMID: 30195015. 2: Moldavan M, Cravetchi O, Allen CN. GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the suprachiasmatic nucleus neurons. J Neurophysiol. 2017 Dec 1;118(6):3092-3106. doi: 10.1152/jn.00194.2017. Epub 2017 Aug 30. PMID: 28855287; PMCID: PMC5814714. 3: Jinzenji A, Sogawa C, Miyawaki T, Wen XF, Yi D, Ohyama K, Kitayama S, Sogawa N, Morita K. Antiallodynic action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a betaine/GABA transporter inhibitor. J Pharmacol Sci. 2014;125(2):217-26. doi: 10.1254/jphs.13146fp. Epub 2014 May 30. PMID: 24881960. 4: Suárez LM, Bustamante J, Orensanz LM, Martín del Río R, Solís JM. Cooperation of taurine uptake and dopamine D1 receptor activation facilitates the induction of protein synthesis-dependent late LTP. Neuropharmacology. 2014 Apr;79:101-11. doi: 10.1016/j.neuropharm.2013.10.035. Epub 2013 Nov 10. PMID: 24225198. 5: Beggiato S, O'Connor WT, Tomasini MC, Antonelli T, Loche A, Tanganelli S, Cacciaglia R, Ferraro L. GET73 increases rat extracellular hippocampal CA1 GABA levels through a possible involvement of local mGlu5 receptor. Synapse. 2013 Oct;67(10):678-91. doi: 10.1002/syn.21672. Epub 2013 May 21. PMID: 23564259. 6: Ransom CB, Tao W, Wu Y, Spain WJ, Richerson GB. Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons. J Neurophysiol. 2013 Feb;109(3):803-12. doi: 10.1152/jn.00460.2012. Epub 2012 Oct 31. PMID: 23114210; PMCID: PMC3567397. 7: Sogawa N, Hazehara Y, Kunitomo M, Morita Y, Yoo B, Ohyama K, Sogawa C, Kitayama S. Age-dependent changes in the susceptibility to thiopental anesthesia in mice: analysis of the relationship to the functional expression of GABA transporter. Pharmacol Biochem Behav. 2012 Dec;103(2):267-72. doi: 10.1016/j.pbb.2012.08.027. Epub 2012 Sep 4. PMID: 22963929. 8: Galvan A, Hu X, Smith Y, Wichmann T. Localization and function of GABA transporters in the globus pallidus of parkinsonian monkeys. Exp Neurol. 2010 Jun;223(2):505-15. doi: 10.1016/j.expneurol.2010.01.018. Epub 2010 Feb 4. PMID: 20138865; PMCID: PMC2864357. 9: Peng XQ, Gardner EL, Xi ZX. Gamma-vinyl GABA increases nonvesicular release of GABA and glutamate in the nucleus accumbens in rats via action on anion channels and GABA transporters. Psychopharmacology (Berl). 2010 Mar;208(4):511-9. doi: 10.1007/s00213-009-1753-7. Epub 2009 Dec 22. PMID: 20033132; PMCID: PMC3713230. 10: Matthews E Jr, Rahnama-Vaghef A, Eskandari S. Inhibitors of the gamma- aminobutyric acid transporter 1 (GAT1) do not reveal a channel mode of conduction. Neurochem Int. 2009 Dec;55(8):732-40. doi: 10.1016/j.neuint.2009.07.005. Epub 2009 Jul 19. PMID: 19622377; PMCID: PMC2764797. 11: Schmitt U, Conner AC, Rapp S, Kissling C, Jennen-Steinmetz C, Hünnerkopf R, Coogan AN, Thome J. The effects of GABA transporter inhibition on synaptophysin and synaptotagmin expression in diazepam tolerance. World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):439-46. doi: 10.1080/15622970902874932. PMID: 19452356. 12: Meinild AK, Loo DDF, Skovstrup S, Gether U, MacAulay N. Elucidating conformational changes in the gamma-aminobutyric acid transporter-1. J Biol Chem. 2009 Jun 12;284(24):16226-16235. doi: 10.1074/jbc.M109.003137. Epub 2009 Apr 10. PMID: 19363027; PMCID: PMC2713550. 13: Ben-Yona A, Kanner BI. Transmembrane domain 8 of the {gamma}-aminobutyric acid transporter GAT-1 lines a cytoplasmic accessibility pathway into its binding pocket. J Biol Chem. 2009 Apr 10;284(15):9727-32. doi: 10.1074/jbc.M809423200. Epub 2009 Feb 6. PMID: 19201752; PMCID: PMC2665093. 14: Tartaglione CM, Ritta MN. On the presence of 3H-GABA uptake mechanism in bovine spermatozoa. Anim Reprod Sci. 2008 Oct;108(1-2):247-58. doi: 10.1016/j.anireprosci.2007.08.010. Epub 2007 Aug 25. PMID: 17954017. 15: Qu L, Liu X, Wu C, Leung LS. Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats. Neurobiol Dis. 2007 Sep;27(3):320-7. doi: 10.1016/j.nbd.2007.06.003. Epub 2007 Jun 12. PMID: 17643307. 16: Wu Y, Wang W, Richerson GB. The transmembrane sodium gradient influences ambient GABA concentration by altering the equilibrium of GABA transporters. J Neurophysiol. 2006 Nov;96(5):2425-36. doi: 10.1152/jn.00545.2006. Epub 2006 Jul 26. PMID: 16870837. 17: Quilichini PP, Chiron C, Ben-Ari Y, Gozlan H. Stiripentol, a putative antiepileptic drug, enhances the duration of opening of GABA-A receptor channels. Epilepsia. 2006 Apr;47(4):704-16. doi: 10.1111/j.1528-1167.2006.00497.x. PMID: 16650136. 18: Mullen GP, Mathews EA, Saxena P, Fields SD, McManus JR, Moulder G, Barstead RJ, Quick MW, Rand JB. The Caenorhabditis elegans snf-11 gene encodes a sodium- dependent GABA transporter required for clearance of synaptic GABA. Mol Biol Cell. 2006 Jul;17(7):3021-30. doi: 10.1091/mbc.e06-02-0155. Epub 2006 Apr 26. PMID: 16641366; PMCID: PMC1483038. 19: Soragna A, Bossi E, Giovannardi S, Pisani R, Peres A. Functionally independent subunits in the oligomeric structure of the GABA cotransporter rGAT1. Cell Mol Life Sci. 2005 Dec;62(23):2877-85. doi: 10.1007/s00018-005-5322-x. PMID: 16314925. 20: Krause S, Schwarz W. Identification and selective inhibition of the channel mode of the neuronal GABA transporter 1. Mol Pharmacol. 2005 Dec;68(6):1728-35. doi: 10.1124/mol.105.013870. Epub 2005 Sep 8. PMID: 16150932.