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

• Inhibition of prostaglandin-induced intestinal secretion by igmesine in healthy volunteers [8].
• CONCLUSIONS: Igmesine, a final sigma ligand, inhibits PGE2-induced intestinal secretion in normal humans [8].
• CONCLUSION: These results show that JO 1784, a selective sigma ligand, is a potent protector of the duodenal mucosa [1].
• The influence of central vs. peripheral administration of sigma ligands (dl- and l-N-allylnormetazocine, 1-3-di-o-tolylguanidine, (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene and phencyclidine on colonic motility was investigated in fasted and fed dogs equipped with strain-guage transducers implanted on proximal and transverse colon [9].
• AIMS: To assess the antisecretory potential of igmesine in cholera toxin, LT, and STa induced water and electrolyte secretion using an in vivo rat model of jejunal perfusion [2].

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

• JO 1784 (50, 75 and 100 mg/kg) provided significant protection against this ischaemia-induced cell death (P < 0.03-0.005) [10].
• CRF (0.6 micrograms i.c.)-induced 83% inhibition of gastric emptying was reversed by 45% by JO 1784 (5 micrograms i.c.). JO 1784 (5-50 micrograms i.c.) did not influence basal gastric function [11].
• Neuropeptide Y and JO 1784, a selective sigma ligand, alter intestinal ion transport through a common, haloperidol-sensitive site [12].
• JO 1784 (3 mg/kg subcutaneously) successfully attenuated this loss of [3H] (+)-pentazocine binding sites in the hippocampus (CA1, CA3 and CA4 regions) and in the substantia innominata [13].

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

• Neuropeptide Y and sigma ligand (JO 1784) suppress stress-induced colonic motor disturbances in rats through sigma and cholecystokinin receptors [3].
• 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 [5].
• The effects of JO 1784 and NPY were evaluated using antagonists of several receptor types [18].
• N-methyl-D-aspartate (NMDA)-induced increases in cGMP was blocked by igmesine indicating that igmesine may interfere with the NMDA receptor/nitric oxide synthase/cGMP pathway [19].
• In the present study we used the olfactory bulbectomy (OBX) animal model of depression to assess the effects of the sigma1 ligand igmesine on OBX-induced behaviour [20].

Analytical, diagnostic and therapeutic context of igmesine

• BACKGROUND & AIMS: Igmesine, a final sigma ligand, has been shown to inhibit intestinal secretion and diarrhea in animal models [8].
• A double-blind crossover study was performed involving intraluminal infusion of PGE2 after oral administration of placebo or igmesine at two doses [8].
• Igmesine reduced immobility duration at 30 versus 60 mg/kg in control groups [21].

References