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Chemical Compound Review

Alphagen     (E)-N-(cyclopropylmethyl)-N- methyl-3,6...

Synonyms: CHEMBL2104866, SureCN7362635, CI-1019, JO-1784, LS-30437, ...
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Disease relevance of igmesine

  • RESULTS: JO 1784 elicited a potent protection against duodenal ulcers but had a weaker protective effect on any of the gastric ulceration models tested [1].
  • The sigma ligand, igmesine, inhibits cholera toxin and Escherichia coli enterotoxin induced jejunal secretion in the rat [2].
  • BMY 14802 (a sigma receptor antagonist) injected s.c. (1 mg/kg) abolished the antagonistic effects of JO 1784 and NPY on the ES-induced colonic hyperkinesia [3].
  • In the present study, we analyzed the antiamnesic and neuroprotective activities of donepezil in a mouse hypoxia model induced by repetitive CO exposure, comparing donepezil's pharmacological profile with other cholinesterase inhibitors tacrine, rivastigmine, and galanthamine, and the reference sigma1 agonist igmesine [4].
  • Four days after intracerebroventricular administration of pertussis toxin (150 ng/kg), both neuropeptide Y and JO 1784, when administered centrally, were unable to antagonize the stress-induced hyperkinesia [5].

Psychiatry related information on igmesine

  • Similarly, prior administration of d-NANM (100 ng/kg) and JO 1784 (50 ng/kg) abolished the caeco-colonic hypermotility induced by psychological stress and intracerebroventricular injection of CRF [5].
  • In the present study the effects of JO 1784 on experimental induced amnesia were investigated using one trial passive avoidance task in rats [6].
  • In the open field apparatus, the CRF-induced increase in the locomotor activity was also reduced by JO 1784 administration [7].

High impact information on igmesine


Chemical compound and disease context of igmesine

  • Of the drugs investigated JO 1784 (0.25, 1.0, 4.0 and 16.0 mg/kg i.p.), (+)-3-PPP (0.25, 1.0 and 4.0 mg/kg i.p.), DTG (1.0, 4.0 and 8.0 mg/kg) and piracetam significantly reversed scopolamine induced amnesia on day 3 (T3) [6].

Biological context of igmesine


Anatomical context of igmesine

  • Several high affinity sigma (sigma) ligands, such as DTG, JO-1784, (+)-pentazocine, BD-737 and L-687,384, administered at low doses act as agonists by potentiating N-methyl-D-aspartate (NMDA)-induced activation of pyramidal neurons in the CA3 region of the rat dorsal hippocampus [14].
  • In TMT-treated rats, JO 1784 produced a significant increase in M2, receptor density in several brain regions with the most marked effects occurring in the amygdaloid nuclei, basal ganglia, cortex, hippocampus and hypothalamus [15].
  • In control rats, JO 1784 alone decreased M1 receptor density in the amygdaloid nuclei, basal ganglia, cortex and hippocampus and decreased M2 receptor density in the amygdaloid nuclei, basal ganglia, cortex, hippocampus, hypothalamus and septal regions [15].
  • Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin-releasing factor-induced inhibition of gastric acid secretion in rats [16].
  • The sigma ligands (+)-pentazocine, igmesine, and 1,3-di(2-tolyl)guanidine (DTG) all reversibly inhibited voltage-activated K+ currents in both cell lines [17].

Associations of igmesine with other chemical compounds

  • Although application of serosal haloperidol had no effect alone up to concentrations of 1 microM, this compound produced a rightward displacement in both the NPY and JO 1784 concentration-effect curves [18].

Gene context of igmesine


Analytical, diagnostic and therapeutic context of igmesine


  1. Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats. Pascaud, X.B., Chovet, M., Soulard, P., Chevalier, E., Roze, C., Junien, J.L. Gastroenterology (1993) [Pubmed]
  2. The sigma ligand, igmesine, inhibits cholera toxin and Escherichia coli enterotoxin induced jejunal secretion in the rat. Turvill, J.L., Kasapidis, P., Farthing, M.J. Gut (1999) [Pubmed]
  3. Neuropeptide Y and sigma ligand (JO 1784) suppress stress-induced colonic motor disturbances in rats through sigma and cholecystokinin receptors. Gue, M., Junien, J.L., Del Rio, C., Bueno, L. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  4. Antiamnesic and neuroprotective effects of donepezil against learning impairments induced in mice by exposure to carbon monoxide gas. Meunier, J., Ieni, J., Maurice, T. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  5. Neuropeptide Y and sigma ligand (JO 1784) act through a Gi protein to block the psychological stress and corticotropin-releasing factor-induced colonic motor activation in rats. Junien, J.L., Gue, M., Bueno, L. Neuropharmacology (1991) [Pubmed]
  6. Evidence for an anti-amnesic effect of JO 1784 in the rat: a potent and selective ligand for the sigma receptor. Earley, B., Burke, M., Leonard, B.E., Gouret, C.J., Junien, J.L. Brain Res. (1991) [Pubmed]
  7. Effect of chronic pretreatment with the sigma ligand JO 1784 on CRF-induced changes in behaviour, neurotransmitter and immunological function in the rat. Song, C., Earley, B., Leonard, B.E. Neuropsychobiology (1997) [Pubmed]
  8. Inhibition of prostaglandin-induced intestinal secretion by igmesine in healthy volunteers. Rozé, C., Bruley Des Varannes, S., Shi, G., Genéve, J., Galmiche, J.P. Gastroenterology (1998) [Pubmed]
  9. Selective stimulation of colonic motor response to a meal by sigma ligands in dogs. Junien, J.L., Gue, M., Pascaud, X., Fioramonti, J., Bueno, L. Gastroenterology (1990) [Pubmed]
  10. The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia. O'Neill, M., Caldwell, M., Earley, B., Canney, M., O'Halloran, A., Kelly, J., Leonard, B.E., Junien, J.L. Eur. J. Pharmacol. (1995) [Pubmed]
  11. Central action of sigma receptor ligand, JO 1784, to suppress CRF-induced inhibition of gastric function in conscious rats. Yoneda, M., Junien, J.L., Taché, Y. Eur. J. Pharmacol. (1992) [Pubmed]
  12. Neuropeptide Y and JO 1784, a selective sigma ligand, alter intestinal ion transport through a common, haloperidol-sensitive site. Rivière, P.J., Pascaud, X., Junien, J.L., Porreca, F. Eur. J. Pharmacol. (1990) [Pubmed]
  13. The sigma ligand JO 1784 prevents trimethyltin-induced behavioural and sigma-receptor dysfunction in the rat. O'Connell, A.W., Earley, B., Leonard, B.E. Pharmacol. Toxicol. (1996) [Pubmed]
  14. Effects of low and high doses of selective sigma ligands: further evidence suggesting the existence of different subtypes of sigma receptors. Bergeron, R., Debonnel, G. Psychopharmacology (Berl.) (1997) [Pubmed]
  15. Effects of JO 1784, a selective sigma ligand, on the autoradiographic localization of M1 and M2 muscarinic receptor subtypes in trimethyltin treated rats. Earley, B., Glennon, M., Leonard, B.E., Junien, J.L. Neurochem. Int. (1995) [Pubmed]
  16. Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin-releasing factor-induced inhibition of gastric acid secretion in rats. Gué, M., Yoneda, M., Mönnikes, H., Junien, J.L., Taché, Y. Br. J. Pharmacol. (1992) [Pubmed]
  17. Inhibition of tumor cell proliferation by sigma ligands is associated with K+ Channel inhibition and p27kip1 accumulation. Renaudo, A., Watry, V., Chassot, A.A., Ponzio, G., Ehrenfeld, J., Soriani, O. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  18. Effects of neuropeptide Y, peptide YY and sigma ligands on ion transport in mouse jejunum. Riviere, P.J., Rao, R.K., Pascaud, X., Junien, J.L., Porreca, F. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  19. Neuropharmacological profile of a selective sigma ligand, igmesine: a potential antidepressant. Akunne, H.C., Zoski, K.T., Whetzel, S.Z., Cordon, J.J., Brandon, R.M., Roman, F., Pugsley, T.A. Neuropharmacology (2001) [Pubmed]
  20. Effects of sigma ligands on NMDA receptor function in the bulbectomy model of depression: a behavioural study in the rat. Bermack, J., Lavoie, N., Dryver, E., Debonnel, G. Int. J. Neuropsychopharmacol. (2002) [Pubmed]
  21. Enhanced antidepressant effect of sigma(1) (sigma(1)) receptor agonists in beta(25-35)-amyloid peptide-treated mice. Urani, A., Romieu, P., Roman, F.J., Maurice, T. Behav. Brain Res. (2002) [Pubmed]
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