(±)-Epibatidine dihydrochloride

Epibatidine dihydrochloride（CAS 162885-01-0）is a highly selective nicotinic acetylcholine receptor (nAChR) agonist. Its biological effects are mediated via nAChR activation and do not directly cross-interact with opioid receptor pathways. In a peripheral immunomodulation model, subcutaneous administration of Epibatidine reduced the proliferative response of rat peripheral blood lymphocytes to a T-cell mitogen. This effect was completely blocked by the peripheral ganglionic nicotinic receptor antagonist chlorisondamine, was not affected by the opioid receptor antagonist naltrexone, and was not observed with central administration, suggesting that its immunomodulatory effect mainly depends on peripheral nAChRs and does not rely on elevated corticosterone levels.

In studies of central nociceptive modulation, Epibatidine can inhibit capsaicin-induced orofacial nociception and hyperalgesia by activating nAChRs in the rat ventrolateral orbital cortex (VLOC). This effect can be blocked by pretreatment with the nicotinic receptor antagonist mecamylamine, indicating that it can participate in nociceptive signal regulation via nAChRs in specific central brain regions, exhibiting nAChR-dependent functions at both peripheral and central sites.

References:

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[2] Tamaddonfard E, Erfanparast A, Abbas Farshid A, Delkhosh-Kasmaie F. Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats. Eur J Pharmacol. 2017 Nov 15;815:399-404. doi: 10.1016/j.ejphar.2017.09.048. Epub 2017 Sep 29. PMID: 28970017.