Effects of the I1 imidazoline/ α 2-adrenergic receptor agonist moxonidine in comparison with clonidine in the formalin test in rats

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Abstract
Moxonidine is a mixed I(1) imidazoline/alpha(2)moxonidine=morphine. The I(1) imidazoline preferring antagonist efaroxan produced a dose-dependent antagonism of both moxonidine (5.0 mg/kg) and clonidine (0.5 mg/kg). In addition, the alpha(2)-adrenergic receptor antagonist yohimbine produced a dose-related antagonism of moxonidine, but only partially antagonized clonidine. Prazosin failed to block the effects of either moxonidine or clonidine, indicating a lack of involvement of alpha(1) as well as alpha(2B) and alpha(2C) receptors. The present results suggest that alpha(2)-adrenergic receptors play an important role in mediating the effects of moxonidine in producing antinociception in the formalin test. Further, the present results demonstrate that the mechanism of action of moxonidine and clonidine differ in that clonidine, but not moxonidine, produces an antinociceptive effect through a yohimbine-insensitive mechanism in the formalin test.