Asimadoline hydrochloride

• CAT Number: R024641
• CAS Number: 185951-07-9
• Molecular Formula: C27H31ClN2O2
• Molecular Weight: 451.00
• Purity: ≥95%
• Synonyms: N-[(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-N-methyl-2,2-diphenylacetamide;hydrochloride
• InChI: InChI=1S/C27H30N2O2.ClH/c1-28(25(21-11-5-2-6-12-21)20-29-18-17-24(30)19-29)27(31)26(22-13-7-3-8-14-22)23-15-9-4-10-16-23;/h2-16,24-26,30H,17-20H2,1H3;1H/t24-,25+;/m0./s1
• InChIKey: GMJSLABTEURMBF-CLSOAGJSSA-N
• SMILES: CN(C(CN1CCC(C1)O)C2=CC=CC=C2)C(=O)C(C3=CC=CC=C3)C4=CC=CC=C4.Cl

Asimadoline (EMD-61753) hydrochloride is an orally active, selective and peripherally active κ-opioid agonist with IC50s of 5.6 nM (guinea pig) and 1.2 nM (human recombinant). Asimadoline hydrochloride has low permeability across the blood brain barrier and has peripheral anti-inflammatory actions. Asimadoline hydrochloride ameliorates allodynia in diabetic rats and has the potential for irritable bowel syndrome (IBS)[1][2][3].
Asimadoline (EMD-61753) hydrochloride has high selectively in κ: μ: δ opioid binding ratios of 1:501:498 in human recombinant receptors. The IC50 for Asimadoline hydrochloride binding to μ-opioid receptors is 3 µM and to δ-opioid receptors is 0.7 µM. The IC50 values for D1, D2, kainate, σ, PCP/NMDA, H1, α1, α2, M1/M2, glycine, 5HT1A, 5HT1C, 5HT1D, 5HT2, 5HT3, AMPA and kainate/AMPA receptors are all >10 µM[1].
Asimadoline hydrochloride has affinity to sodium and L type Ca2+ ion channels at IC50 concentrations 150 to 800 fold the IC50 for the κ receptors[1].
At high concentrations, Asimadoline hydrochloride demonstrates spasmolytic action against 400 µM barium chloride in the rat duodenum (IC50=4.2 µM), suggesting that Asimadoline hydrochloride may block the direct stimulant effects of barium on smooth muscle through mechanisms that are not identified[1].
Asimadoline (EMD-61753 hydrochloride; 1, 5, 15 mg/kg; s.c.) acutely ameliorates both formalin-evoked hyperalgesia and tactile allodynia in diabetic rats[3].
The absorption rate following oral administration is 80% in rats and >90% in dogs and monkeys. The metabolism of Asimadoline hydrochloride is rapid and appears similar in animals and man. Asimadoline hydrochloride has peripheral anti-inflammatory actions that are partly mediated through increase in joint fluid substance P levels[1].
Treatment with Asimadoline hydrochloride (5 mg/kg/day; i.p.) produces marked (and sustained) attenuation of the disease with all three time regimes[2].

Reference

[1]. Camilleri M, et al. Asimadoline, a κ-Opioid Agonist, and Visceral Sensation. Neurogastroenterol Motil. 2008 Sep; 20(9): 971–979.
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[2]. Binder W, et al. Involvement of substance P in the anti-inflammatory effects of the peripherally selective kappa-opioid asimadoline and the NK1 antagonist GR205171. Eur J Neurosci. 1999 Jun;11(6):2065-72.
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[3]. C G Jolivalt, et al. Dynorphin A, kappa opioid receptors and the antinociceptive efficacy of asimadoline in streptozotocin-induced diabetic rats. Diabetologia. 2006 Nov;49(11):2775-85.
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