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

Linopirine     1-phenyl-3,3-bis(pyridin-4- ylmethyl)indol...

Synonyms: AVIVA, Linopirdine, Lopac-L-134, Tocris-1999, L134_ALDRICH, ...
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 C13780


Psychiatry related information on C13780


High impact information on C13780

  • Retigabine-induced currents in CHO-KCNQ2/Q3 cells were inhibited by 60.6 +/- 11% (n = 4) by the KCNQ2/Q3 blocker, linopirdine (10 microM), and 82.7 +/- 5.4% (n = 4) by BaCl(2) (10 mM) [9].
  • In voltage-clamp experiments using large myelinated fibres, the selective KCNQ channel blockers XE991 (IC50 = 2.2 microm) and linopirdine (IC50 = 5.5 microm) completely inhibited I(Ks), as did TEA (IC50 = 0.22 mm) [10].
  • In contrast, in aged rats linopirdine caused widespread expression of Fos throughout neocortex [11].
  • Modulation of spontaneous and stimulation-evoked transmitter release from rat sympathetic neurons by the cognition enhancer linopirdine: insights into its mechanisms of action [12].
  • Furthermore, linopirdine potently targets nAChRs to modulate stimulus-secretion coupling in adrenal chromaffin cells [13].

Biological context of C13780


Anatomical context of C13780

  • The mechanisms by which the cognition enhancer linopirdine may affect transmitter release were investigated in cultures of rat superior cervical ganglion neurons [12].
  • Linopirdine (10 microM) reduced inward currents through the low-voltage-activated K(+) current in type I hair cells, but concentrations up to 200 microM had little effect on steady-state outward K(+) current in these cells [17].
  • The present study examines the possible involvement of channels which mediate the movement of K+, Cl- and Na+, which are important to the polarization state of excitable membranes, in the release-enhancing effects of linopirdine [5].
  • The mechanism involved in the blockade of M-current by linopirdine was studied in cultured rat superior cervical sympathetic ganglia using whole-cell patch clamp recording [18].
  • Effect of the putative cognitive enhancer, linopirdine (DuP 996), on quantal parameters of acetylcholine release at the frog neuromuscular junction [19].

Associations of C13780 with other chemical compounds

  • In this study we have monitored by Fos immunohistochemistry the effect of the acetylcholine release enhancer linopirdine (DUP996) on the immediate early gene c-fos in brains of 3 months and 30 months old rats [11].
  • The M-current blockers, linopirdine (DuP 996; 3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one) and XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone), inhibited the activation of the KCNQ5 channel induced by the BMS-204352 [20].
  • The voltage-independent current reversed at the equilibrium potential for potassium ( E(K)), hence was carried by a K+ conductance, and was blocked by the selective KCNQ channel blockers XE991 and linopirdine [21].
  • Furthermore, apamin and paxilline, specific blockers of Ca(2+)-activated SKand BK-type K(+) channels, respectively; E-4031, a blocker of ether a-go-go K(+) channel; and linopirdine, a blocker of M-type K(+) channel, did not affect the agonist-specific patterns of calcium signaling and PRL secretion [22].

Gene context of C13780

  • The KCNQ4 channels were blocked in a voltage-independent manner by the memory-enhancing M current blockers XE-991 and linopirdine with IC(50) values of 5.5 and 14 microM, respectively [23].
  • Furthermore, the sensitivity of KCNQ5/Q3 channels to linopirdine supports the possibility that potassium channels comprised of KCNQ5 and KCNQ3 may make a contribution to native M-currents [24].
  • This compound demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices, and the inhibition mediated by (S)-2 was reversed by the KCNQ blocker linopirdine [25].
  • Linopirdine, a tool useful in targeting native or heterologous KCNQ channels, was used to study the role of KCNQ channels in the guinea pig cochlea [1].
  • CYP induction increased the metabolism of linopirdine [26].

Analytical, diagnostic and therapeutic context of C13780

  • RESULTS: Bath perfusion of linopirdine induced epileptiform activity only in slices from neonatal rats [27].
  • Our study examines the selectivity of linopirdine for IM by determining its effects on other ionic currents present in rat hippocampal CA1 neurons using patch clamp techniques [28].
  • Inhibitors of M-channels, such as linopirdine and 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE991), enhance depolarization-induced transmitter release and improve learning performance in animal models [29].
  • The subjects who received linopirdine did not experience clinically important changes in vital signs, electrocardiograms (ECGs), electroencephalograms (EEGs), or clinical laboratory evaluations [16].
  • Linopirdine plasma and urine samples were quantified after liquid extraction by a specific HPLC method using UV detection [16].


  1. Degeneration of sensory outer hair cells following pharmacological blockade of cochlear KCNQ channels in the adult guinea pig. Nouvian, R., Ruel, J., Wang, J., Guitton, M.J., Pujol, R., Puel, J.L. Eur. J. Neurosci. (2003) [Pubmed]
  2. Effects of the memory enhancer linopirdine (Dup 996) on cerebral glucose metabolism in naive and hypoxia-exposed rats. Dent, G.W., Rule, B.L., Tam, S.W., De Souza, E.B. Brain Res. (1993) [Pubmed]
  3. General pharmacology of the putative cognition enhancer linopirdine. Flagmeyer, I., Gebert, I., van der Staay, F.J. Arzneimittel-Forschung. (1995) [Pubmed]
  4. The P1 component of the middle latency auditory evoked potential predicts a practice effect during clinical trials in Alzheimer's disease. Green, J.B., Elder, W.W., Freed, D.M. Neurology (1995) [Pubmed]
  5. Studies on the role of K+, Cl- and Na+ ion permeabilities in the acetylcholine release enhancing effects of linopirdine (DuP 996) in rat cortical slices. Maciag, C.M., Logue, A.R., Tinker, W.J., Saydoff, J.A., Tam, S.W., Zaczek, R. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  6. MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice. Murai, S., Saito, H., Abe, E., Masuda, Y., Odashima, J., Itoh, T. J. Neural Transm. Gen. Sect. (1994) [Pubmed]
  7. Linopiridine (DUP 996; AVIVA): its effects in the Morris water escape tank and on retention of an incompletely acquired bar-press response in rodents. Flagmeyer, I., Van Der Staay, F.J. Pharmacol. Biochem. Behav. (1995) [Pubmed]
  8. Sound sequence discrimination learning is dependent on cholinergic inputs to the rat auditory cortex. Kudoh, M., Seki, K., Shibuki, K. Neurosci. Res. (2004) [Pubmed]
  9. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Wickenden, A.D., Yu, W., Zou, A., Jegla, T., Wagoner, P.K. Mol. Pharmacol. (2000) [Pubmed]
  10. KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier. Schwarz, J.R., Glassmeier, G., Cooper, E.C., Kao, T.C., Nodera, H., Tabuena, D., Kaji, R., Bostock, H. J. Physiol. (Lond.) (2006) [Pubmed]
  11. The acetylcholine release enhancer linopirdine induces Fos in neocortex of aged rats. Dent, G.W., Rule, B.L., Zhan, Y., Grzanna, R. Neurobiol. Aging (2001) [Pubmed]
  12. Modulation of spontaneous and stimulation-evoked transmitter release from rat sympathetic neurons by the cognition enhancer linopirdine: insights into its mechanisms of action. Kristufek, D., Koth, G., Motejlek, A., Schwarz, K., Huck, S., Boehm, S. J. Neurochem. (1999) [Pubmed]
  13. Linopirdine modulates calcium signaling and stimulus-secretion coupling in adrenal chromaffin cells by targeting M-type K+ channels and nicotinic acetylcholine receptors. Dzhura, E.V., He, W., Currie, K.P. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  14. Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells. Yeung, S.Y., Greenwood, I.A. Br. J. Pharmacol. (2005) [Pubmed]
  15. [3H]linopirdine binding to rat brain membranes is not relevant for M-channel interaction. Wolff, C., Gillard, M., Fuks, B., Chatelain, P. Eur. J. Pharmacol. (2005) [Pubmed]
  16. Single-dose pharmacokinetics, safety, and tolerance of linopirdine (DuP 996) in healthy young adults and elderly volunteers. Pieniaszek, H.J., Fiske, W.D., Saxton, T.D., Kim, Y.S., Garner, D.M., Xilinas, M., Martz, R. Journal of clinical pharmacology. (1995) [Pubmed]
  17. Effects of KCNQ channel blockers on K(+) currents in vestibular hair cells. Rennie, K.J., Weng, T., Correia, M.J. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  18. Inhibition of M-current in cultured rat superior cervical ganglia by linopirdine: mechanism of action studies. Costa, A.M., Brown, B.S. Neuropharmacology (1997) [Pubmed]
  19. Effect of the putative cognitive enhancer, linopirdine (DuP 996), on quantal parameters of acetylcholine release at the frog neuromuscular junction. Provan, S.D., Miyamoto, M.D. Br. J. Pharmacol. (1994) [Pubmed]
  20. Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. Dupuis, D.S., Schrøder, R.L., Jespersen, T., Christensen, J.K., Christophersen, P., Jensen, B.S., Olesen, S.P. Eur. J. Pharmacol. (2002) [Pubmed]
  21. Voltage-independent KCNQ4 currents induced by (+/-)BMS-204352. Schrøder, R.L., Strøbaek, D., Olesen, S.P., Christophersen, P. Pflugers Arch. (2003) [Pubmed]
  22. Dependence of prolactin release on coupling between Ca(2+) mobilization and voltage-gated Ca(2+) influx pathways in rat lactotrophs. Tomić, M., Andric, S.A., Stojilkovic, S.S. Endocrine (2003) [Pubmed]
  23. KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. Søgaard, R., Ljungstrøm, T., Pedersen, K.A., Olesen, S.P., Jensen, B.S. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  24. Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. Wickenden, A.D., Zou, A., Wagoner, P.K., Jegla, T. Br. J. Pharmacol. (2001) [Pubmed]
  25. (S)-N-[1-(4-cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide is a potent and efficacious KCNQ2 opener which inhibits induced hyperexcitability of rat hippocampal neurons. Wu, Y.J., Boissard, C.G., Chen, J., Fitzpatrick, W., Gao, Q., Gribkoff, V.K., Harden, D.G., He, H., Knox, R.J., Natale, J., Pieschl, R.L., Starrett, J.E., Sun, L.Q., Thompson, M., Weaver, D., Wu, D., Dworetzky, S.I. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
  26. Induction of cytochromes P-450 2B and 3A in mice following the dietary administration of the novel cognitive enhancer linopirdine. Diamond, S., Rakestraw, D., O'Neil, J., Lam, G.N., Christ, D.D. Drug Metab. Dispos. (1994) [Pubmed]
  27. Epileptiform activity induced by pharmacologic reduction of M-current in the developing hippocampus in vitro. Peña, F., Alavez-Pérez, N. Epilepsia (2006) [Pubmed]
  28. Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage-dependent and calcium-activated potassium currents in hippocampal neurons. Schnee, M.E., Brown, B.S. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  29. Newly developed blockers of the M-current do not reduce spike frequency adaptation in cultured mouse sympathetic neurons. Romero, M., Reboreda, A., Sánchez, E., Lamas, J.A. Eur. J. Neurosci. (2004) [Pubmed]
WikiGenes - Universities