Dexmedetomidine enhances the local anesthetic action of lidocaine via an alpha-2A adrenoceptor.
BACKGROUND
Clonidine, an alpha-2 adrenoceptor agonist, is a common adjunct in both central and peripheral blocks. Dexmedetomidine, a more selective alpha-2 adrenoceptor agonist, is also known to enhance central neural blockades. Its peripheral effect, however, has not been fully elucidated. Thus, we evaluated the effect of dexmedetomidine and other alpha-2 adrenoceptor agonists on the local anesthetic action of lidocaine at the periphery and explored the mechanism involved.


METHODS
alpha-2 Adrenoceptor agonists, including dexmedetomidine, clonidine, and oxymetazoline, combined with lidocaine were intracutaneously injected into the back of male guinea pigs. The test of six pinpricks was applied every 5 min until 60 min after the injection. The number of times which the prick failed to elicit a response during the 60-min period was added and the sum served as an anesthetic score indicating the degree of local anesthesia. Differences from the control value within the group were analyzed using an analysis of variance followed by a post hoc Dunnett's test. Furthermore, we evaluated the antagonism of the effect of dexmedetomidine by yohimbine, an alpha-2A, 2B, and 2C adrenoceptor antagonist, or prazosin, an alpha-1, alpha-2B, and 2C adrenoceptor antagonist, analyzed using a two-way analysis of variance.


RESULTS
All alpha-2 adrenoceptor agonists enhanced the degree of local anesthesia of lidocaine in a dose-dependent manner. Furthermore, yohimbine inhibited the effect of dexmedetomidine, whereas prazosin did not.


CONCLUSIONS
We demonstrated that alpha-2 adrenoceptor agonists enhanced the local anesthetic action of lidocaine, and suggest that dexmedetomidine acts via alpha-2A adrenoceptors.
Yoshitomi
Tatsushi
T
Department of Dental Anesthesiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Kohjitani
Atsushi
A
Maeda
Shigeru
S
Higuchi
Hitoshi
H
Shimada
Masahiko
M
Miyawaki
Takuya
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D020927:Dexmedetomidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000779:Anesthetics, Local; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D020927:Dexmedetomidine; D010109:Oxymetazoline; D008012:Lidocaine; D003000:Clonidine; D011224:Prazosin