Linopirdine | CAS#105431-72-9 | cognitive enhancer

MedKoo Cat#: 562333 | Name: Linopirdine

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Description:

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

Linopirdine is a cognitive enhancer. It acts by stimulating release of acetylcholine and other neurotransmitters.

Chemical Structure

Linopirdine

CAS#105431-72-9

Theoretical Analysis

MedKoo Cat#: 562333

Name: Linopirdine

CAS#: 105431-72-9

Chemical Formula: C26H21N3O

Exact Mass: 391.1685

Molecular Weight: 391.47

Elemental Analysis: C, 79.77; H, 5.41; N, 10.73; O, 4.09

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 #

113168-57-3 (HCl) 105431-72-9

Synonym

Linopirdine; DuP 996; DuP-996; DuP996;

IUPAC/Chemical Name

1,3-Dihydro-1-phenyl-3,3-bis(4-pyridinylmethyl)-2H-indol-2-one

InChi Key

YEJCDKJIEMIWRQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H21N3O/c30-25-26(18-20-10-14-27-15-11-20,19-21-12-16-28-17-13-21)23-8-4-5-9-24(23)29(25)22-6-2-1-3-7-22/h1-17H,18-19H2

SMILES Code

O=C1N(C2=CC=CC=C2)C3=C(C=CC=C3)C1(CC4=CC=NC=C4)CC5=CC=NC=C5

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

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:

Linopirdine (DuP 996) is an orally active, selective M-type K+ current (IM; Kv7; KCNQ Channels) inhibitor with an IC50 of 2.4 μM.

In vitro activity:

Linopirdine induces increases in intracellular calcium concentration in human embryonic kidney 293 (HEK293) cells expressing TRPV1, but not TRPA1 and TRPM8 or in wild-type HEK293 cells. Linopirdine also activates an inward current in TRPV1-expressing HEK293 cells that is almost completely blocked by the selective TRPV1 antagonist capsazepine. Reference: J Pharmacol Sci. 2010;114(3):332-40. https://pubmed.ncbi.nlm.nih.gov/21099148/

In vivo activity:

Anesthetized male Sprague-Dawley rats were instrumented with arterial and venous catheters for blood pressure monitoring, hemorrhage and fluid resuscitation. Linopirdine transiently (10-15 min) and dose-dependently increased MAP by up to 15%. Reference: J Biomed Sci. 2017 Jan 17;24(1):8. https://pubmed.ncbi.nlm.nih.gov/28095830/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	76.63
	DMSO	75.0	191.58
	Ethanol	30.0	76.63
	Ethanol:PBS (pH 7.2) (1:30)	0.0	0.08

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 391.47 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. Neacsu C, Babes A. The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1. J Pharmacol Sci. 2010;114(3):332-40. doi: 10.1254/jphs.10172fp. PMID: 21099148. 2. Schnee ME, Brown BS. Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage-dependent and calcium-activated potassium currents in hippocampal neurons. J Pharmacol Exp Ther. 1998 Aug;286(2):709-17. PMID: 9694925. 3. Nassoiy SP, Byron KL, Majetschak M. Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats. J Biomed Sci. 2017 Jan 17;24(1):8. doi: 10.1186/s12929-017-0316-1. PMID: 28095830; PMCID: PMC5240358. 4. Gong SS, Chang Q, Ding J. Inhibition of potassium currents in outer hair cells and Deiters' cells from guinea pig cochlea by linopirdine. Sheng Li Xue Bao. 2004 Aug 25;56(4):531-8. PMID: 15322692.

In vitro protocol:

In vivo protocol:

1. Nassoiy SP, Byron KL, Majetschak M. Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats. J Biomed Sci. 2017 Jan 17;24(1):8. doi: 10.1186/s12929-017-0316-1. PMID: 28095830; PMCID: PMC5240358. 2. Gong SS, Chang Q, Ding J. Inhibition of potassium currents in outer hair cells and Deiters' cells from guinea pig cochlea by linopirdine. Sheng Li Xue Bao. 2004 Aug 25;56(4):531-8. PMID: 15322692.

1: Greene DL, Kang S, Hoshi N. XE991 and Linopirdine Are State-Dependent Inhibitors for Kv7/KCNQ Channels that Favor Activated Single Subunits. J Pharmacol Exp Ther. 2017 Jul;362(1):177-185. doi: 10.1124/jpet.117.241679. Epub 2017 May 8. PubMed PMID: 28483800; PubMed Central PMCID: PMC5478917. 2: Kang SW, Ahn JW, Ahn SC. Inhibition of K(+) outward currents by linopirdine in the cochlear outer hair cells of circling mice within the first postnatal week. Korean J Physiol Pharmacol. 2017 Mar;21(2):251-257. doi: 10.4196/kjpp.2017.21.2.251. Epub 2017 Feb 21. PubMed PMID: 28280419; PubMed Central PMCID: PMC5343059. 3: Nassoiy SP, Byron KL, Majetschak M. Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats. J Biomed Sci. 2017 Jan 17;24(1):8. doi: 10.1186/s12929-017-0316-1. PubMed PMID: 28095830; PubMed Central PMCID: PMC5240358. 4: Ghezzi F, Corsini S, Nistri A. Electrophysiological characterization of the M-current in rat hypoglossal motoneurons. Neuroscience. 2017 Jan 6;340:62-75. doi: 10.1016/j.neuroscience.2016.10.048. Epub 2016 Oct 27. PubMed PMID: 27984184. 5: Stott JB, Barrese V, Greenwood IA. Kv7 Channel Activation Underpins EPAC-Dependent Relaxations of Rat Arteries. Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2404-2411. Epub 2016 Oct 27. PubMed PMID: 27789473; PubMed Central PMCID: PMC5467728. 6: Cox RH, Fromme S. Functional Expression Profile of Voltage-Gated K(+) Channel Subunits in Rat Small Mesenteric Arteries. Cell Biochem Biophys. 2016 Jun;74(2):263-76. doi: 10.1007/s12013-015-0715-4. PubMed PMID: 27286858; PubMed Central PMCID: PMC4905591. 7: Devaux J, Abidi A, Roubertie A, Molinari F, Becq H, Lacoste C, Villard L, Milh M, Aniksztejn L. A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity. Epilepsia. 2016 May;57(5):e87-93. doi: 10.1111/epi.13366. Epub 2016 Mar 31. PubMed PMID: 27030113. 8: Yang JE, Song MS, Shen Y, Ryu PD, Lee SY. The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization. Int J Mol Sci. 2016 Mar 18;17(3):407. doi: 10.3390/ijms17030407. PubMed PMID: 26999128; PubMed Central PMCID: PMC4813262. 9: Hedegaard ER, Johnsen J, Povlsen JA, Jespersen NR, Shanmuganathan JA, Laursen MR, Kristiansen SB, Simonsen U, Bøtker HE. Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury. J Pharmacol Exp Ther. 2016 Apr;357(1):94-102. doi: 10.1124/jpet.115.230409. Epub 2016 Feb 11. PubMed PMID: 26869667. 10: Goodwill AG, Fu L, Noblet JN, Casalini ED, Sassoon D, Berwick ZC, Kassab GS, Tune JD, Dick GM. KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine. Am J Physiol Heart Circ Physiol. 2016 Mar 15;310(6):H693-704. doi: 10.1152/ajpheart.00688.2015. Epub 2016 Jan 29. PubMed PMID: 26825518; PubMed Central PMCID: PMC4865062. 11: Jepps TA, Olesen SP, Greenwood IA, Dalsgaard T. Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats. Br J Pharmacol. 2016 May;173(9):1478-90. doi: 10.1111/bph.13444. Epub 2016 Feb 26. PubMed PMID: 26802314; PubMed Central PMCID: PMC4831315. 12: Greenberg HZ, Shi J, Jahan KS, Martinucci MC, Gilbert SJ, Vanessa Ho WS, Albert AP. Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels. Vascul Pharmacol. 2016 May;80:75-84. doi: 10.1016/j.vph.2016.01.001. Epub 2016 Jan 6. PubMed PMID: 26772767; PubMed Central PMCID: PMC4830458. 13: Engholm M, Pinilla E, Mogensen S, Matchkov V, Hedegaard ER, Chen H, Mulvany MJ, Simonsen U. Involvement of transglutaminase 2 and voltage-gated potassium channels in cystamine vasodilatation in rat mesenteric small arteries. Br J Pharmacol. 2016 Mar;173(5):839-55. doi: 10.1111/bph.13393. Epub 2016 Jan 27. PubMed PMID: 26603619; PubMed Central PMCID: PMC4761098. 14: Sakakibara K, Feng GG, Li J, Akahori T, Yasuda Y, Nakamura E, Hatakeyama N, Fujiwara Y, Kinoshita H. Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K(+) channels. J Pharmacol Sci. 2015 Sep;129(1):31-7. doi: 10.1016/j.jphs.2015.07.042. Epub 2015 Aug 10. PubMed PMID: 26318674. 15: Abd-Elsayed AA, Ikeda R, Jia Z, Ling J, Zuo X, Li M, Gu JG. KCNQ channels in nociceptive cold-sensing trigeminal ganglion neurons as therapeutic targets for treating orofacial cold hyperalgesia. Mol Pain. 2015 Jul 31;11:45. doi: 10.1186/s12990-015-0048-8. PubMed PMID: 26227020; PubMed Central PMCID: PMC4521366. 16: Barrese V, Taglialatela M, Greenwood IA, Davidson C. Protective role of Kv7 channels in oxygen and glucose deprivation-induced damage in rat caudate brain slices. J Cereb Blood Flow Metab. 2015 Oct;35(10):1593-600. doi: 10.1038/jcbfm.2015.83. Epub 2015 May 13. PubMed PMID: 25966943; PubMed Central PMCID: PMC4640310. 17: Stott JB, Povstyan OV, Carr G, Barrese V, Greenwood IA. G-protein βγ subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity. Proc Natl Acad Sci U S A. 2015 May 19;112(20):6497-502. doi: 10.1073/pnas.1418605112. Epub 2015 May 4. PubMed PMID: 25941381; PubMed Central PMCID: PMC4443360. 18: Mills TA, Greenwood SL, Devlin G, Shweikh Y, Robinson M, Cowley E, Hayward CE, Cottrell EC, Tropea T, Brereton MF, Dalby-Brown W, Wareing M. Activation of KV7 channels stimulates vasodilatation of human placental chorionic plate arteries. Placenta. 2015 Jun;36(6):638-44. doi: 10.1016/j.placenta.2015.03.007. Epub 2015 Mar 21. PubMed PMID: 25862611. 19: Morales-Cano D, Moreno L, Barreira B, Pandolfi R, Chamorro V, Jimenez R, Villamor E, Duarte J, Perez-Vizcaino F, Cogolludo A. Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycaemia. Cardiovasc Res. 2015 Apr 1;106(1):98-108. doi: 10.1093/cvr/cvv020. Epub 2015 Jan 23. PubMed PMID: 25616413. 20: Stott JB, Barrese V, Jepps TA, Leighton EV, Greenwood IA. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats. Hypertension. 2015 Mar;65(3):676-82. doi: 10.1161/HYPERTENSIONAHA.114.04373. Epub 2014 Dec 29. PubMed PMID: 25547342.