Effects of the I-1 imidazoline/alpha(2)-adrenergic receptor agonist moxonidine in comparison with clonidine in the formalin test in rats

Moxonidine is a mixed I-1 imidazoline/alpha(2)-adrenergic receptor agonist structurally related to clonidine. In the present studies, moxonidine, like clonidine, produced a dose- and time-related inhibition of formalin-induce d behaviors after subcutaneous administration. Moxonidine was equiefficacio us to both clonidine and morphine in inhibiting formalin-induced behaviors. The order of potencies of these analgesics was clonidine > moxonidine = mo rphine. The I-1 imidazoline preferring antagonist efaroxan produced a dose- dependent antagonism of both moxonidine (5.0 mg/kg) and clonidine (0.5 mg/k g). In addition, the alpha(2)-adrenergic receptor antagonist yohimbine prod uced a dose-related antagonism of moxonidine, but only partially antagonize d clonidine. Prazosin failed to block the effects of either moxonidine or c lonidine, indicating a lack of involvement of alpha(1) as well as alpha(2B) and alpha(2C) receptors. The present results suggest that alpha(2)-adrener gic receptors play an important role in mediating the effects of moxonidine in producing antinociception in the formalin test. Further, the present re sults demonstrate that the mechanism of action of moxonidine and clonidine differ in that clonidine, but not moxonidine, produces an antinociceptive e ffect through a yohimbine-insensitive mechanism in the formalin test. (C) 2 000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.