Cat. No.: HY-169914A

Igmesine

Name: Igmesine
Brand: MedChemExpress
SKU: HY-169914A
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(Synonyms: JO 1784)

Igmesine (JO 1784) is a selective σ-1 receptor agonist (IC₅₀ = 39 nM) with oral activity and blood-brain barrier penetration. Igmesine stimulates duodenal bicarbonate secretion in rats via a σ1/vagal/CCK-A-dependent pathway, without antisecretory activity. Igmesine centrally blocks CRF-mediated gastrin-inhibitory effects, and in TMT toxicity and MCAO focal ischemia models, it downregulates PTBBS, reduces NOS, and modulates M1/M2 density. Igmesine is used in research on duodenal ulcers, Alzheimer's disease, and related diseases.

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CAS No.: 140850-73-3
화학식: C₂₃H₂₉N
분자량:319.49

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Igmesine Chemical Structure

CAS No.: 140850-73-3

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Biological Activity
- 제품 설명
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
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References
Calculators
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Classifications
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Biological Activity

제품 설명

IC₅₀ & Target

^[1]

σ1

39 nM (IC₅₀)

All Sigma Receptor Isoforms :

In Vitro

Igmesine is a highly selective σ receptor ligand with strong in vitro binding affinity for σ sites, whereas its enantiomer JO 1783 shows negligible σ receptor binding activity^[2].
Igmesine binds potently and selectively to σ sites in rat brain membrane preparations with an IC₅₀ of 39 nM; it shows extremely low affinity for the phencyclidine binding site of the NMDA receptor and exhibits no significant affinity for the other 23 receptor sites tested^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Aβ/Tau/α-Synuclein AggregationOxidative StressOthers

Aβ/Tau/α-Synuclein Aggregation

Igmesine (0.03 mg/kg i.p.; once daily; for 7 consecutive days) acts synergistically with FENM to alleviate Aβ_25-35-induced learning impairment in mice in both short-term and long-term memory tests^[3].

Oxidative Stress

Igmesine (2.5-10 mg/kg; i.p.; multiple injections at 5-45 min and 3-54 h after occlusion) exerts neuroprotective effects in a mouse model of focal cerebral ischemia, and at all tested doses, it significantly inhibits ischemia-induced increases in ω₃ site density and significantly suppresses ischemia-induced increases in NOS activity^[5].

Others

Igmesine (0.01-0.5 μg; intracerebroventricular injection; single dose; 10 min before intracisternal injection of CRF, Bombesin (HY-P0195), or hIL-1β) dose-dependently blocks the inhibitory effect of CRF on pentagastrin-stimulated gastric acid secretion, and this effect is CRF-specific and is blocked by pretreatment with BMY 14802 (HY-153091)^[1].
Igmesine (0.03 μg; microinjected into the paraventricular nucleus (PVN) or lateral hypothalamus (LH); single dose; 10 min before microinjection of corticotropin-releasing factor (CRF) into the same nucleus) microinjected into the PVN completely blocks the inhibitory effect of CRF on pentagastrin-stimulated gastric acid secretion, whereas microinjection into the LH has no such effect^[1].
Igmesine (1-10 mg/kg; p.o.; administered orally 1 h before cysteamine; single dose) potently protects rats against cysteamine-induced duodenal ulcers with an oral ED₅₀ of 4.14 mg/kg, and this activity is blocked by σ receptor antagonists and peripheral cholecystokinin A receptor antagonists^[2].
Igmesine (p.o.) mildly protects rat gastric mucosa from injury, with oral ED₅₀ values ranging from 25.2 to 55.4 mg/kg depending on the ulcerogenic stimulus^[2].
Igmesine (1-30 mg/kg; intradermal injection; single dose) does not inhibit gastric acid secretion in pylorus-ligated rats at high doses^[2].
Igmesine (0.25-2 mg/kg; intravenous injection; single bolus) stimulates duodenal bicarbonate secretion in Rattus norvegicus in vivo in a dose-dependent manner, and this activity is mediated by σ receptors, vagal pathways, and peripheral cholecystokinin A receptors^[2].
Igmesine (1.2-3.5 mg/kg; i.p., p.o.; single dose; 30 min before radiotracer injection) is a highly potent, selective, and well-tolerated σ-site ligand in mice, with ID₅₀ values for in vivo displacement of (+)-[³H]SKF 10,047 binding to σ sites of 1.2 mg/kg for i.p. administration and 3.5 mg/kg for p.o. administration^[4].
Igmesine (1-16 mg/kg; i.p.; once daily; for 40 days) exerts neuroprotective effects against trimethyltin-induced muscarinic receptor loss in male Sprague-Dawley rats, attenuating the reduction in M₁ and M₂ receptor density in multiple brain regions, with the most pronounced effects in the cortex, hippocampus, amygdala, and hypothalamus^[6].
Igmesine (1-16 mg/kg; i.p.; once daily; for 40 days) decreases M₁ and M₂ muscarinic receptor density in multiple brain regions of healthy male Sprague-Dawley rats^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Sprague-Dawley albino (male, 250-350 g, fasted 18 h before study, anaesthetized with urethane)^[1]
Dosage:

0.01 μg; 0.1 μg; 0.5 μg
Administration:

i.c.; single dose; 10 minutes prior to intracisternal injection of CRF, bombesin, or hIL-1β
Result:

Did not modify pentagastrin-stimulated gastric acid secretion.
Dose-dependently prevented CRF-induced 72% inhibition of pentagastrin-stimulated gastric acid secretion.
Completely abolished the CRF effect at the 0.5 μg dose.
Did not alter the 56% inhibition induced by bombesin or the 62% inhibition induced by hIL-1β at the 0.5 μg dose.
Lost the ability to block CRF-induced inhibition of gastric acid secretion when rats were pretreated subcutaneously with BMY 14802.

Animal Model:

Sprague-Dawley albino (male, 250-350 g, fasted 18 h before study, anaesthetized with urethane, guide cannulae implanted 7 days prior using dissociative anaesthetic/sedative analgesic anaesthesia)^[1]
Dosage:

0.03 μg
Administration:

microinjection into PVN or LH; single dose; 10 minutes prior to microinjection of CRF into the same nucleus
Result:

Did not modify pentagastrin-stimulated gastric acid secretion when microinjected into the PVN.
Completely prevented the 61% inhibition of pentagastrin-stimulated gastric acid secretion induced by CRF microinjected into the PVN, with gastric acid output reaching 184 μmol/90 min compared to 76 μmol/90 min in the CRF-only group.
Did not alter the 51% inhibition of pentagastrin-stimulated gastric acid secretion induced by CRF microinjected into the LH when microinjected into the LH.

Animal Model:

Sprague-Dawley (male, 180-220 g, cysteamine-induced duodenal ulcers)^[2]
Dosage:

1-10 mg/kg
Administration:

p.o.; single dose 1 hour before cysteamine
Result:

Induced 15% inhibition of the ulcer index.
Induced 48% inhibition of the ulcer index.
Induced 71% inhibition of the ulcer index, reducing mean ulcer index from 33.2 mm² to 9.7 mm².
Exhibited an ED₅₀ of 4.14 mg/kg p.o. for ulcer protection.
Lost ulceroprotective effect when pretreated with haloperidol, BMY 14,802, or devazepide.

Animal Model:

Sprague-Dawley (male, 250-400 g, pylorus-ligated Shay rat preparation)^[2]
Dosage:

1-30 mg/kg
Administration:

i.d.; single dose immediately after pylorus ligation
Result:

Did not significantly modify gastric acid volume, free acid concentration or output, or total acid concentration or output at any tested dose.

Animal Model:

Sprague-Dawley (male, 250-400 g, in situ cannulated duodenum preparation under Inactin anesthesia)^[2]
Dosage:

0.25 mg/kg; 0.5 mg/kg; 1 mg/kg; 2 mg/kg
Administration:

i.v.; single bolus
Result:

Induced a dose-dependent increase in duodenal bicarbonate output, with a threshold dose of 0.25 mg/kg i.v.
Increased bicarbonate output from a basal 7.60 μEq·cm^-1·h^-1 to a plateau of 14.8 μEq·cm^-1·h^-1 at 1 mg/kg i.v., which persisted for 2 hours.
Did not further increase bicarbonate secretion at 2 mg/kg i.v.
Lost stimulatory effect when pretreated with bilateral vagotomy, tetrodotoxin, hexamethonium, haloperidol, BMY 14,802, or devazepide.
Retained stimulatory effect when pretreated with atropine, SCH 23,390, sulpiride, prazosin, yohimbine, naloxone, or indomethacin.
Retained stimulatory effect after intracerebroventricular administration of devazepide.

Animal Model:

Swiss OF-1 (male, 7-9 weeks old, weight 32 g)^[3]
Dosage:

0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 0.03 mg/kg (combined with 0.01 mg/kg FENM)
Administration:

i.p.; daily; 7 days
Result:

Prevented Aβ_25-35-induced spontaneous alternation deficits.
Showed less effectiveness on passive avoidance deficits.
Produced synergistic protection (combination index < 1) in both Y-maze spontaneous alternation test and passive avoidance test when combined with 0.01 mg/kg FENM.

Animal Model:

Swiss mice (male, 20-22 g)^[4]
Dosage:

1.2 mg/kg (i.p.); 3.5 mg/kg (p.o.); up to 600 mg/kg (p.o., toxicity); >1000 mg/kg (p.o., LD₅₀)
Administration:

i.p.; single dose; 30 minutes prior to radiotracer injection; p.o.; single dose; 30 minutes prior to radiotracer injection
Result:

Displaced (+)-[³H]SKF 10,047 from brain σ-sites with an ID₅₀ of 1.2 mg/kg (i.p.).
Displaced (+)-[³H]SKF 10,047 from brain σ-sites with an ID₅₀ of 3.5 mg/kg (p.o.).
Inhibited σ-site binding by at least 60% four hours after i.p. administration.
Inhibited σ-site binding by 30% four hours after p.o. administration.
Showed no toxic effects at oral doses up to 600 mg/kg.
Had an LD₅₀ > 1000 mg/kg orally.

Animal Model:

Swiss mice (4-week-old male, 20-25 g, OF-1 Iffa Credo, France)^[5]
Dosage:

2.5 mg/kg; 5.0 mg/kg; 10.0 mg/kg
Administration:

i.p.; multiple doses at 5, 15, 45 min and 3, 6, 18, 24, 36, 48, 54 h post-occlusion
Result:

Reduced ipsilateral cortical ω₃ site densities to 74.89 pmol/mg protein at 2.5 mg/kg, 126.22 pmol/mg protein at 5.0 mg/kg, and 116.16 pmol/mg protein at 10.0 mg/kg.
Caused no changes in contralateral cortical ω₃ site densities at any dose.
Reduced cerebellar NOS activity to 0.1622 pmol/μg protein/h and brain-stem NOS activity to 0.1502 pmol/μg protein/h at 2.5 mg/kg.
Reduced cerebellar NOS activity to 0.2168 pmol/μg protein/h and brain-stem NOS activity to 0.0894 pmol/μg protein/h at 5.0 mg/kg.
Reduced cerebellar NOS activity to 0.1280 pmol/μg protein/h and brain-stem NOS activity to 0.0914 pmol/μg protein/h at 10.0 mg/kg.
Reduced infarct volume to 16.355 mm³ at 2.5 mg/kg, 13.484 mm³ at 5.0 mg/kg, and 16.320 mm³ at 10.0 mg/kg.

Animal Model:

Sprague-Dawley (male, mean body weight 280-320 g, neurotoxicity model via single i.p. injection of trimethyltin chloride)^[6]
Dosage:

1 mg/kg; 4 mg/kg; 16 mg/kg
Administration:

i.p.; daily; 40 days
Result:

Produced significant increases in M₁ receptor density in the cortex, olfactory regions, septum, thalamus, and basal forebrain nuclei.
Prevented 65-67% of trimethyltin-induced M₁ receptor loss in the septum at 1 and 4 mg/kg, and 22% at 16 mg/kg, with additional protection in the substantia innominata and ventral pallidum across all doses.
Caused a small 1-3% decrease in M₁ receptor density in the hippocampal CA₂ and CA₃ regions.
Attenuated trimethyltin-induced M₂ receptor loss with significant increases in the amygdaloid nuclei (5-12% increase), basal ganglia (5-8% increase), frontal-parietal motor cortex layers III-IV (17-27% increase), hippocampal CA₁ (9-10% increase), CA₂ (13-16% increase), CA₃ (11-12% increase), and hypothalamus (22-31% increase).

Animal Model:

Sprague-Dawley (male, mean body weight 280-320 g)^[6]
Dosage:

1 mg/kg; 4 mg/kg; 16 mg/kg
Administration:

i.p.; daily; 40 days
Result:

Decreased M₁ receptor density in the amygdaloid nuclei, basal ganglia, cortex, and hippocampus, with the greatest decrease (33%) in the hippocampal CA₁ field at 1 mg/kg, and a 17% decrease in the nucleus accumbens at 1 mg/kg.
Decreased M₂ receptor density in the amygdaloid nuclei, basal ganglia, cortex, hippocampus, hypothalamus, and septal regions, with significant reductions observed across multiple subregions of these areas at various doses.

Related Protocols :

Alzheimer’s Disease Modeling

Chemical Information

CAS No. 140850-73-3
분자량 319.49
화학식 C₂₃H₂₉N
SMILES

C(N(CC1CC1)C)(C/C=C/C2=CC=CC=C2)(CC)C3=CC=CC=C3
Synonyms

JO 1784
선적

Room temperature in continental US; may vary elsewhere.
보관

Please store the product under the recommended conditions in the Certificate of Analysis.

순도&문서

Handling Instructions (2659 KB)

References

[1]. Gué M, et al. Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin-releasing factor-induced inhibition of gastric acid secretion in rats. British journal of pharmacology. 1992 Nov;107(3):642-7.

[2]. Pascaud XB, et al. Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats. Gastroenterology. 1993 Feb;104(2):427-34. [Content Brief]

[3]. Freyssin A, et al. Fluoroethylnormemantine (FENM) shows synergistic protection in combination with a sigma-1 receptor agonist in a mouse model of Alzheimer's disease. Neuropharmacology. 2024 Jan 01;242:109733.

[4]. Roman FJ, et al. JO 1784, a potent and selective ligand for rat and mouse brain sigma-sites. The Journal of pharmacy and pharmacology. 1990 Jun;42(6):439-40. [Content Brief]

[5]. Earley B, et al. The effects of MK-801, ifenprodil, JO 1784, JO 1994 and JO 1997 on PK 11195 receptor binding, nitric oxide synthase (NO synthase) activity and infarct volume in a mouse model of focal cerebral ischaemia. Neurochem Int. 1996 May-Jun;28(5-6):509-21.

[6]. Earley B, et al. Effects of JO 1784, a selective sigma ligand, on the autoradiographic localization of M1 and M2 muscarinic receptor subtypes in trimethyltin treated rats. Neurochem Int. 1995 Jun;26(6):559-70.

Calculators

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Igmesine

All Sigma Receptor Isoforms