Asimadoline (EMD-61753) hydrochloride is an orally active, selective and peripherally active κ-opioid agonist with IC 50 s 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)
In Vitro
Asimadoline (EMD-61753) hydrochloride has high selectively in κ: μ: δ opioid binding ratios of 1:501:498 in human recombinant receptors. The IC 50 for Asimadoline hydrochloride binding to μ-opioid receptors is 3 µM and to δ-opioid receptors is 0.7 µM. The IC 50 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. Asimadoline hydrochloride has affinity to sodium and L type Ca 2+ ion channels at IC 50 concentrations 150 to 800 fold the IC 50 for the κ receptors. At high concentrations, Asimadoline hydrochloride demonstrates spasmolytic action against 400 µM barium chloride in the rat duodenum (IC 50 =4.2 µM), suggesting that Asimadoline hydrochloride may block the direct stimulant effects of barium on smooth muscle through mechanisms that are not identified. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Asimadoline (EMD-61753 hydrochloride; 1, 5, 15 mg/kg; s.c.) acutely ameliorates both formalin-evoked hyperalgesia and tactile allodynia in diabetic rats. 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 . Treatment with Asimadoline hydrochloride (5 mg/kg/day; i.p.) produces marked (and sustained) attenuation of the disease with all three time regimes. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Adult female Sprague-Dawley ratsDosage: 1, 5, 15 mg/kg Administration: SC; single dose Result: Acutely ameliorated both formalin-evoked hyperalgesia and tactile allodynia in diabetic rats.
Form:Solid
IC50& Target:IC50: 5.6 nM (guinea pig κ opioid), 1.2 nM (human recombinant κ opioid)
