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Nishiyama, T. et al.

Nishiyama, Gyermek, Trudell, Hanaoka,

Spinally mediated analgesia and receptor binding affinity of epibatidine analogs.

Two epibatidine derivatives, (1R, 2R, 5S)-A-(2-chloropyridinyl) azabicyclo [3.2.1] octane; A=2 beta: analog 1, 2 alpha: analog 2, were investigated for their spinally mediated analgesic effects and binding affinity to nicotinic acetylcholine receptors. The tail flick response and behavioral side effects were studied after intrathecal agents in rats. The membrane preparations of the Torpedo Californica and rat cerebral cortices were used for radioligand binding utilizing [3H] epibatidine displacement. Their affinity to muscular and neuronal nicotinic acetylcholine receptors and spinally mediated analgesic potencies were 15, 20, and 3.8 times (analog 1) and 2000, 30,000, and 3.3 times (analog 2) less than epibatidine, respectively. Two times the analgesic 50% effective doses (ED(50)s) of the analogs did not induce side effects, while one-third of that of epibatidine induced motor disturbance. In summary, the two epibatidine analogs have higher potency ratio of spinally mediated analgesia/side effects than epibatidine.[1]

References

Spinally mediated analgesia and receptor binding affinity of epibatidine analogs. Nishiyama, T., Gyermek, L., Trudell, M.L., Hanaoka, K. Eur. J. Pharmacol. (2003) [Pubmed]

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