Acta Pharmacologica Sinica (2009) 30: 1227–1236; doi: 10.1038/aps.2009.129

Aim: To assess whether epinephrine, phenylephrine, and methoxamine act via certain subtypes of adrenoceptors to exert their local anesthetic activity. 

Methods: We investigated cutaneous anesthesia from adrenoceptor agonists and/or antagonists in conscious, unanesthetized Sprague-Dawley male rats (weight 200− 250 g ).  Cutaneous anesthesia was evidenced by a block of the cutaneous trunci muscle reflex, which is characterized by reflex movement of the skin over the back produced by twitches of lateral thoracispinal muscles in response to local dorsal cutaneous noxious pinprick.

Results: Local infiltration of epinephrine, L-phenylephrine, or methoxamine alone induces cutaneous anesthesia in rats in a dose-dependent way.  Epinephrine is found to be 19 and 29 times more potent than those of methoxamine and L-phenylephrine, respectively.  The cutaneous anesthesia induced by epinephrine, phenylephrine, or methoxamine can be significantly reduced by α₁-adrenoceptor antagonists (eg, prazosin), α1, α2-adrenoceptor antagonist, α _1A -adrenoceptor antagonist (eg, 5-methylurapdil), α_1B-adrenoceptor antagonist (eg, chloroethylclonidine), or α_1D-adrenoceptor antagonist (eg, BMY7873). 

Conclusion: Our results indicate that epinephrine, phenylephrine and methoxamine all act mainly via mixed subtypes of α₁-adrenoceptors to induce cutaneous anesthesia in the rat. 

Keywords: anesthesia; epinephrine; vasoconstriction; phenylephrine; methoxamine