Asimadoline

Asimadoline (EMD-61753) 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 has low permeability across the blood brain barrier and has peripheral anti-inflammatory actions. Asimadoline ameliorates allodynia in diabetic rats and has the potential for irritable bowel syndrome (IBS)^[1][2][3]. IC50 & Target: IC50: 5.6 nM (guinea pig κ opioid), 1.2 nM (human recombinant κ opioid)^[1] In Vitro: Asimadoline (EMD-61753) has high selectively in κ: μ: δ opioid binding ratios of 1:501:498 in human recombinant receptors. The IC₅₀ for Asimadoline 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 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 demonstrates spasmolytic action against 400 µM barium chloride in the rat duodenum (IC₅₀=4.2 µM), suggesting that Asimadoline may block the direct stimulant effects of barium on smooth muscle through mechanisms that are not identified^[1].
In Vivo: Asimadoline (EMD-61753; 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 is rapid and appears similar in animals and man. Asimadoline has peripheral anti-inflammatory actions that are partly mediated through increase in joint fluid substance P levels^[1].
Treatment with Asimadoline (5 mg/kg/day; i.p.) produces marked (and sustained) attenuation of the disease with all three time regimes^[2].