| Identification | Back Directory | [Name]
A 582941 | [CAS]
848591-90-2 | [Synonyms]
A 582941
A 582941; A582941
A-582941 dihydrochloride
Octahydro-2-methyl-5-(6-phenyl-3-pyridazinyl)-pyrrolo[3,4-c]pyrrole
Pyrrolo[3,4-c]pyrrole, octahydro-2-Methyl-5-(6-phenyl-3-pyridazinyl)-, dihydrochloride
Pyrrolo[3,4-c]pyrrole, octahydro-2-methyl-5-(6-phenyl-3-pyridazinyl)-, hydrochloride (1:2)
(3aR,6aS)-2-methyl-5-(6-phenylpyridazin-3-yl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole
2-methyl-5-(6-phenylpyridazin-3-yl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole:dihydrochloride | [Molecular Formula]
C17H21ClN4 | [MOL File]
848591-90-2.mol | [Molecular Weight]
316.83 |
| Hazard Information | Back Directory | [Uses]
A 582941 has been shown to provide glycogen synthase kinase-3β activation and α7 nicotinic receptors in Aβ1-42-induced tau phosphorylation in PC12 cells, which is useful in neurodegeneration associated with Alzheimer''s disease research. | [Biological Activity]
a 582941 is a highly selective partial agonist of α7 nicotinic acetylcholine receptors (nachrs), with an ec50 value of 4260 nm to human α7 nachrs [1].nachrs are a family of pentameric ligand-gated ion channels. they are derived from multiple α (α2-α10) and β (β2-β4) subunit genes. α7 nachr receptor exhibits higher ca2+ permeability than other nachr combinations. these receptors modulate the release of multiple neurotransmitters, including acetylcholine (ach), glutamate, and gaba [1].in flipr, a 582941 did not activate recombinant heteromeric nachrs (α4β2, α3β2, α3β4, or α4β4) according to ca2+ dynamics results. in imr-32 cells expressing native human α3β4 nachrs, a 582941 did not produce an agonist effect (with an efficacy less than 20% at concentrations up to 100,000 nm). in xenopus oocytes expressing an α9α10 nachr construct, a 582941 at concentrations up to 100,000 nm did not evoke currents. with respect to nachrs, a 582941 activated only the homomeric α7 subtype [1].in a rat model of short-term memory based on olfactory cues, saline-treated adults used investigation times during the second session nearly equal to the first session, exhibiting little recognition of the juvenile. treatment with a 582941 in adult rats resulted in a dose-related reduction in the exploration time during the second session compared with the first session, exhibiting improved recognition of the juvenile [1]. | [in vivo]
A-582941 (3 μM/kg, i.p. once daily for 3 d) induces a moderate increase in ACh release in the medial prefrontal cortex (mPFCx) of freely moving rats[2].
A-582941 (0.01-1.00 μM/kg, i.p.) produces a dose-dependent increase in ERK1/2 phosphorylation in the cingulate cortex and hippocampus, and increases cAMP response element-binding protein (CREB) phosphorylation in the cingulate cortex in mice[2].
A-582941 (0.1-1.0 μM/kg, i.p.) evokes dose-dependent increases in Ser-9 GSK-3β phosphorylation in the mouse cingulate cortex[2].
A-582941 shows high oral bioavailability (mouse ~100%, rat 90%, dog 22%, monkey 50%) and Cmax (mouse 18, rat 114, dog 79, monkey 39 ng/mL) following oral administration (mouse 1.0, rat 6.2, dog 3.0, monkey 3.0 μM/kg)[2].
A-582941 shows terminal elimination half-lives (mouse 1.4, rat 1.5, dog 1.4, monkey 2.0 h), plasma clearance (mouse 7.9, rat 4.7, dog 5.3, monkey 1.6 L/h/kg) and volumes of distribution (mouse 11.4, rat 9.2, dog 7.9, monkey 3.9 L/kg) following intravenous administration (mouse 1.0, rat 6.2, dog 0.5, monkey 0.5 μM/kg)[2]. | Animal Model: | Male Sprague-Dawley CD rats (250-275 g)[2] | | Dosage: | 3 μM/kg | | Administration: | I.p. once daily for 3 days | | Result: | Increased the releases of Ach.
The effect remained stable after the second and third administration.
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| [IC 50]
α7 nAChR: 10.8 nM (Ki, for rat α7 receptors); α7 nAChR: 16.7 nM (Ki, for human α7 receptors); 5-HT3 Receptor: 150 nM (Ki) | [storage]
Desiccate at RT | [References]
[1]. tietje kr, anderson dj, bitner rs, et al. preclinical characterization of a-582941: a novel α7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties. cns neuroscience & therapeutics, 2008, 14(1): 65-82. |
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