The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Lemakalim     (3S,4S)-3-hydroxy-2,2- dimethyl-4-(2...

Synonyms: Levanex, Cromakalim, Levcromakalim, Levcromakelim, CHEMBL100, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Levcromakalim


Psychiatry related information on Levcromakalim

  • 2. The hypoxia-induced amnesia was reduced by cromakalim, a K+ channel opener (KCO), given 10 min before or immediately after the hypoxic treatment [5].

High impact information on Levcromakalim

  • Furthermore, exposure to the K+ ionophore valinomycin or the K+-channel opener cromakalim induced apoptosis [6].
  • Catalase, which dismutates H(2)O(2) to form water and oxygen, inhibited EDHF-mediated relaxation and hyperpolarization, but it did not affect endothelium-independent relaxation following treatment with the K(+) channel opener levcromakalim [7].
  • We investigated whether selective activation of ATP-sensitive K (KATP) channels causes net cellular K loss by examining the effects of the KATP channel agonist cromakalim on unidirectional K efflux, total tissue K content, and action potential duration (APD) in isolated arterially perfused rabbit interventricular septa [1].
  • During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone [8].
  • There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%) [9].

Chemical compound and disease context of Levcromakalim


Biological context of Levcromakalim

  • After 60 minutes of reperfusion following 30 minutes of ischemia, recovery of function was similar, with a trend toward better recovery of developed tension (to 58 +/- 9% versus 39 +/- 10% of control; p = 0.18) and tissue ATP levels in cromakalim-treated hearts but no differences in APD or rest tension [14].
  • We have investigated the effect of a potassium channel opener, BRL 38227, on antigen-induced bronchoconstriction and airway microvascular leakage in sensitized guinea pigs by simultaneously measuring pulmonary resistance (Rl) and extravasation of Evans blue dye [15].
  • The third transmembrane domain of SUR is found to be an important determinant of the response to cromakalim, which possibly harbors at least part of its binding site [16].
  • Lemakalim significantly improved the recovery of left ventricular developed pressure from 49(7)% in control hearts to 65(3)%, and left ventricular end diastolic pressure from 41(3) to 21(4) mm Hg [17].
  • 8. The K+ channel openers cromakalim (BRL 34915) and lemakalim (BRL 38227) did not affect the membrane potential of GCECs or BAECs.(ABSTRACT TRUNCATED AT 400 WORDS)[18]

Anatomical context of Levcromakalim


Associations of Levcromakalim with other chemical compounds

  • The therapeutically important K(+) channel openers (e.g. pinacidil, cromakalim, nicorandil) act specifically on the SUR2 muscle isoforms but, except for diazoxide, remain ineffective on the SUR1 neuronal/pancreatic isoform [23].
  • An apparent competition between sulfonylureas and potassium channel openers occurred in bioassays, and outward potassium currents, previously inhibited by glibenclamide, were partially recovered after application of cromakalim [24].
  • Diazoxide shortened ischemic action potential duration significantly less than cromakalim at equicardioprotective concentrations [3].
  • Both effects disappear after removal of the endothelium and are depressed by tetraethylammonium (3 x 10(-3) M), a rather nonspecific blocker of K+ channels, but not by glibenclamide (10(-5) M), a potent blocker of the ATP-regulated K+ channels, which has a marked effect on the relaxation induced by BRL 38227 [25].
  • Pretreatment of these hearts with 60 microM cromakalim significantly decreased indexes of contractile function but caused a significant improvement of postreperfusion function and a significant decrease in release of lactate dehydroxygenase and in end-diastolic pressure [26].

Gene context of Levcromakalim


Analytical, diagnostic and therapeutic context of Levcromakalim

  • In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma [9].
  • The application of cromakalim that was started from the onset of reperfusion also improved the contractile recovery during this phase and this effect was associated with enhanced APD shortening [2].
  • During aerobic perfusion, 5 microM cromakalim shortened action potential duration (APD) from 217 +/- 7 to 201 +/- 10 msec, had no effect on [K+]o, and reduced tension by 17 +/- 3% (n = 11) [14].
  • Activation of the KATP channel by cromakalim inhibited alpha 2D constriction with greater potency than alpha 1D (EC50, 7.0 +/- 0.2 versus 6.3 +/- 0.1) [32].
  • BRL 38227 (200 micrograms/kg) was administered intravenously 1 min before intravenous dye injection (30 mg/kg); OA (3 mg/ml) was inhaled using an ultrasonic nebulizer (for 30 s) 1 min after dye injection [15].


  1. Mechanism of hypoxic K loss in rabbit ventricle. Shivkumar, K., Deutsch, N.A., Lamp, S.T., Khuu, K., Goldhaber, J.I., Weiss, J.N. J. Clin. Invest. (1997) [Pubmed]
  2. Pharmacological evidence for the persistent activation of ATP-sensitive K+ channels in early phase of reperfusion and its protective role against myocardial stunning. Shigematsu, S., Sato, T., Abe, T., Saikawa, T., Sakata, T., Arita, M. Circulation (1995) [Pubmed]
  3. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels. Possible mechanism of cardioprotection. Garlid, K.D., Paucek, P., Yarov-Yarovoy, V., Murray, H.N., Darbenzio, R.B., D'Alonzo, A.J., Lodge, N.J., Smith, M.A., Grover, G.J. Circ. Res. (1997) [Pubmed]
  4. Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia/reperfusion-induced injury. Heart function studies in nonfibrillating isolated hearts. Tosaki, A., Hellegouarch, A. J. Am. Coll. Cardiol. (1994) [Pubmed]
  5. Antiamnesic action of cromakalim, a potassium channel opener, in mice treated with hypoxia- and cerebral ischemia-type stress stimuli. Nakao, K., Tokuyama, S., Takahashi, M., Kaneto, H., Ueda, H. Cell. Mol. Neurobiol. (1998) [Pubmed]
  6. Mediation of neuronal apoptosis by enhancement of outward potassium current. Yu, S.P., Yeh, C.H., Sensi, S.L., Gwag, B.J., Canzoniero, L.M., Farhangrazi, Z.S., Ying, H.S., Tian, M., Dugan, L.L., Choi, D.W. Science (1997) [Pubmed]
  7. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. Matoba, T., Shimokawa, H., Nakashima, M., Hirakawa, Y., Mukai, Y., Hirano, K., Kanaide, H., Takeshita, A. J. Clin. Invest. (2000) [Pubmed]
  8. ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. Wiener, C.M., Dunn, A., Sylvester, J.T. J. Clin. Invest. (1991) [Pubmed]
  9. Attenuation of nocturnal asthma by cromakalim. Williams, A.J., Lee, T.H., Cochrane, G.M., Hopkirk, A., Vyse, T., Chiew, F., Lavender, E., Richards, D.H., Owen, S., Stone, P. Lancet (1990) [Pubmed]
  10. KATP channel modulation in working rat hearts with coronary occlusion: effects of cromakalim, cicletanine, and glibenclamide. Ferdinandy, P., Szilvássy, Z., Droy-Lefaix, M.T., Tarrade, T., Koltai, M. Cardiovasc. Res. (1995) [Pubmed]
  11. Effects of pinacidil and cromakalim (BRL 34915) on bladder function in rats with detrusor instability. Malmgren, A., Andersson, K.E., Sjögren, C., Andersson, P.O. J. Urol. (1989) [Pubmed]
  12. High-calcium diet enhances vasorelaxation in nitric oxide-deficient hypertension. Jolma, P., Kalliovalkama, J., Tolvanen, J.P., Kööbi, P., Kähönen, M., Hutri-Kähönen, N., Wu, X., Pörsti, I. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  13. Effect of levcromakalim on hypoxia-, KCl- and prostaglandin F2 alpha-induced contractions in isolated rat pulmonary artery. Zhang, F., Morice, A.H. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  14. Activation of ATP-sensitive K+ channels by cromakalim. Effects on cellular K+ loss and cardiac function in ischemic and reperfused mammalian ventricle. Venkatesh, N., Stuart, J.S., Lamp, S.T., Alexander, L.D., Weiss, J.N. Circ. Res. (1992) [Pubmed]
  15. Antigen-induced airway responses are inhibited by a potassium channel opener. Ichinose, M., Miura, M., Takahashi, T., Yamauchi, H., Nakajima, N., Igarashi, A., Ishikawa, J., Inoue, H., Maeyama, K., Watanabe, T. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
  16. A transmembrane domain of the sulfonylurea receptor mediates activation of ATP-sensitive K(+) channels by K(+) channel openers. D'hahan, N., Jacquet, H., Moreau, C., Catty, P., Vivaudou, M. Mol. Pharmacol. (1999) [Pubmed]
  17. Effects of potassium channel modulation during global ischaemia in isolated rat heart with and without cardioplegia. Galiñanes, M., Shattock, M.J., Hearse, D.J. Cardiovasc. Res. (1992) [Pubmed]
  18. Effects of vasoactive agonists on the membrane potential of cultured bovine aortic and guinea-pig coronary endothelium. Mehrke, G., Pohl, U., Daut, J. J. Physiol. (Lond.) (1991) [Pubmed]
  19. Beta 2-adrenergic dilation of resistance coronary vessels involves KATP channels and nitric oxide in conscious dogs. Ming, Z., Parent, R., Lavallée, M. Circulation (1997) [Pubmed]
  20. BRL 34915 (cromakalim) activates ATP-sensitive K+ current in cardiac muscle. Sanguinetti, M.C., Scott, A.L., Zingaro, G.J., Siegl, P.K. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  21. Hormone-regulated K+ channels in follicle-enclosed oocytes are activated by vasorelaxing K+ channel openers and blocked by antidiabetic sulfonylureas. Honoré, E., Lazdunski, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  22. Differential sensitivity of venular and arteriolar alpha-adrenergic receptor constriction to inhibition by hypoxia. Role of receptor subtype and coupling heterogeneity. Leech, C.J., Faber, J.E. Circ. Res. (1996) [Pubmed]
  23. The molecular basis of the specificity of action of K(ATP) channel openers. Moreau, C., Jacquet, H., Prost, A.L., D'hahan, N., Vivaudou, M. EMBO J. (2000) [Pubmed]
  24. Evidence for the existence of a sulfonylurea-receptor-like protein in plants: modulation of stomatal movements and guard cell potassium channels by sulfonylureas and potassium channel openers. Leonhardt, N., Marin, E., Vavasseur, A., Forestier, C. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  25. Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats. Van de Voorde, J., Vanheel, B., Leusen, I. Circ. Res. (1992) [Pubmed]
  26. Specific block of the anti-ischemic actions of cromakalim by sodium 5-hydroxydecanoate. McCullough, J.R., Normandin, D.E., Conder, M.L., Sleph, P.G., Dzwonczyk, S., Grover, G.J. Circ. Res. (1991) [Pubmed]
  27. Synthetic peroxisome proliferator-activated receptor-gamma agonists restore impaired vasorelaxation via ATP-sensitive K+ channels by high glucose. Kinoshita, H., Azma, T., Iranami, H., Nakahata, K., Kimoto, Y., Dojo, M., Yuge, O., Hatano, Y. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  28. The potassium channel opener BRL 38227 inhibits binding of [125I]-labelled endothelin-1 to rat cardiac membranes. Waugh, C.J., Dockrell, M.E., Haynes, W.G., Olverman, H.J., Williams, B.C., Webb, D.J. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  29. Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. Sheppard, D.N., Welsh, M.J. J. Gen. Physiol. (1992) [Pubmed]
  30. Differential effects of endothelin-1 on the vasorelaxant properties of benzopyran and non-benzopyran potassium channel openers. Lawson, K., Barras, M., Zazzi-Sudriez, E., Martin, D.J., Armstrong, J.M., Hicks, P.E. Br. J. Pharmacol. (1992) [Pubmed]
  31. Multiple mechanisms in the smooth muscle relaxant action of calcitonin gene-related peptide (CGRP) in the guinea-pig ureter. Maggi, C.A., Giuliani, S., Santicioli, P. Naunyn Schmiedebergs Arch. Pharmacol. (1994) [Pubmed]
  32. ATP-sensitive K+ channels mediate alpha 2D-adrenergic receptor contraction of arteriolar smooth muscle and reversal of contraction by hypoxia. Tateishi, J., Faber, J.E. Circ. Res. (1995) [Pubmed]
WikiGenes - Universities