ASIMADOLINE

Asimadoline (EMD-61753) has high selectively in κ: μ: δ opioid binding ratios of 1:501:498 in human recombinant receptors. The IC ₅₀ for Asimadoline 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.
It 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 demonstrates spasmolytic action against 400 μM barium chloride in the rat duodenum (IC ₅₀ =4.2 μM), suggesting that Asimadoline may block the direct stimulant effects of barium on smooth muscle through mechanisms that are not identified.

Asimadoline (EMD-61753; 1, 5, 15 mg/kg; sc) 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 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.

IC50: 5.6 nM (guinea pig κ opioid), 1.2 nM (human recombinant κ opioid)