(+)-Igmesine hydrochloride (JO1784) is an orally active and selective σ 1 receptor ligand with an IC50 of 39 nM. (+)-Igmesine hydrochloride binds σ 1 receptors to activate G-proteins and modulate Ca 2+ uptake. (+)-Igmesine (hydrochloride) attenuates ischaemia-induced nitric oxide synthase activity and hyperactivity. (+)-Igmesine hydrochloride can be used for the research of duodenal ulcers, gastric ulcers, and cerebral ischaemia [1] [2] [3] [4].
In Vivo, (+)-Igmesine (1-10 mg/kg; p.o.; single dose) hydrochloride potently protects rats from cysteamine-induced duodenal ulcers, with an ED50 of 4.14 mg/kg p.o. and a 71% reduction in ulcer index at 10 mg/kg p.o[1]. (+)-Igmesine (p.o.; single dose) hydrochloride weakly protects rats from multiple models of gastric mucosal damage, with ED50 values ranging from 25.2 to 55.4 mg/kg p.o[1]. (+)-Igmesine (1-30 mg/kg; i.d.; single dose) hydrochloride does not exhibit gastric antisecretory activity in pylorus-ligated rats[1]. (+)-Igmesine (0.25-2 mg/kg; i.v.; single bolus) hydrochloride dose-dependently stimulates duodenal bicarbonate secretion in anesthetized rat[1]. (+)-Igmesine (25-100 mg/kg; p.o.; at 1, 24, and 48 hours post-surgery) hydrochloride provides statistically significant neuroprotection against ischaemia-induced hippocampal CA1 neuronal death in gerbils[2]. (+)-Igmesine (100 mg/kg; i.p.; at 30 minutes, 6, 24, and 48 hours post-surgery) hydrochloride significantly attenuates ischaemia-induced hyperactivity and increases in NO synthase activity in the hippocampus and brain stem of gerbils[2].
In Vitro, (+)-Igmesine (1 nM-10 μM; 52 h) hydrochloride potently suppresses Phytohemagglutinin-P -, Concanavalin A -, and pokeweed mitogen-stimulated proliferation of rat lymphocytes with reductions in tritiated thymidine uptake[4]. (+)-Igmesine (1 nM-10 μM; 40 min-52 h) hydrochloride exhibits dose-dependent suppression of rat neutrophil phagocytosis and mitogen-stimulated rat lymphocyte proliferation[4].
References:
[1]. Pascaud XB, et al. Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats. Gastroenterology. 1993;104(2):427-434.
[2]. O'Neill M, et al. The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia. Eur J Pharmacol. 1995;283(1-3):217-225.
[3]. Yoneda M, et al. Central action of sigma receptor ligand, JO 1784, to suppress CRF-induced inhibition of gastric function in conscious rats. Eur J Pharmacol. 1992;223(2-3):197-199.
[4]. Song C, et al. Comparison between the effects of sigma receptor ligand JO 1784 and neuropeptide Y on immune functions. Eur J Pharmacol. 1998;345(1):79-87.
In Vivo, (+)-Igmesine (1-10 mg/kg; p.o.; single dose) hydrochloride potently protects rats from cysteamine-induced duodenal ulcers, with an ED50 of 4.14 mg/kg p.o. and a 71% reduction in ulcer index at 10 mg/kg p.o[1]. (+)-Igmesine (p.o.; single dose) hydrochloride weakly protects rats from multiple models of gastric mucosal damage, with ED50 values ranging from 25.2 to 55.4 mg/kg p.o[1]. (+)-Igmesine (1-30 mg/kg; i.d.; single dose) hydrochloride does not exhibit gastric antisecretory activity in pylorus-ligated rats[1]. (+)-Igmesine (0.25-2 mg/kg; i.v.; single bolus) hydrochloride dose-dependently stimulates duodenal bicarbonate secretion in anesthetized rat[1]. (+)-Igmesine (25-100 mg/kg; p.o.; at 1, 24, and 48 hours post-surgery) hydrochloride provides statistically significant neuroprotection against ischaemia-induced hippocampal CA1 neuronal death in gerbils[2]. (+)-Igmesine (100 mg/kg; i.p.; at 30 minutes, 6, 24, and 48 hours post-surgery) hydrochloride significantly attenuates ischaemia-induced hyperactivity and increases in NO synthase activity in the hippocampus and brain stem of gerbils[2].
In Vitro, (+)-Igmesine (1 nM-10 μM; 52 h) hydrochloride potently suppresses Phytohemagglutinin-P -, Concanavalin A -, and pokeweed mitogen-stimulated proliferation of rat lymphocytes with reductions in tritiated thymidine uptake[4]. (+)-Igmesine (1 nM-10 μM; 40 min-52 h) hydrochloride exhibits dose-dependent suppression of rat neutrophil phagocytosis and mitogen-stimulated rat lymphocyte proliferation[4].
References:
[1]. Pascaud XB, et al. Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats. Gastroenterology. 1993;104(2):427-434.
[2]. O'Neill M, et al. The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia. Eur J Pharmacol. 1995;283(1-3):217-225.
[3]. Yoneda M, et al. Central action of sigma receptor ligand, JO 1784, to suppress CRF-induced inhibition of gastric function in conscious rats. Eur J Pharmacol. 1992;223(2-3):197-199.
[4]. Song C, et al. Comparison between the effects of sigma receptor ligand JO 1784 and neuropeptide Y on immune functions. Eur J Pharmacol. 1998;345(1):79-87.