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

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.

Characterization of the hypothermic effects of imidazoline I2 receptor agonists in rats

“…Activation of I 1 receptors has also been shown to decrease body temperature (Cambridge and Robinson, 2005). However the hypothermic effects observed in this study are unlikely to be due to I 1 receptor agonism both because most I 2 receptor ligands have low affinity at I 1 receptors (nM vs. µM, Table 1) and because the I 1 receptor antagonist/α 2 adrenoceptor antagonist efaroxan, at a dose that significantly blocks the antinociceptive effects of a selective I 1 receptor agonist moxonidine (Shannon and Lutz, 2000), did not attenuate the hypothermic effects of I 2 receptor agonists (Figure 4). In fact, efaroxan slightly potentiated the hypothermic effects, which could be due to its 5‐HT 1A receptor partial agonist property (Kleven et al ., 2005).…”

α2‐Agonists as analgesic agents

“…149,150 When administered s.c. moxonidine produced a dose and time-dependent analgesic effect in the formalin test, reducing formalin-induced behaviors both in phase I and in phase II. 151 The use of specific antagonists like efaroxan, yohimbine and prazosine in the above test evidenced that the antinociceptive effect of moxonidine, in the formalin test, is primarily mediated by a 2 -adrenoceptors rather than I 1 receptors. The analgesic properties of moxonidine were extensively studied by researchers of the University of Minnesota who demonstrated that moxonidine produces antinociception in mice in tail flick test and substance P nociceptive test after intrathecal administration.…”

Pharmacological profiles of alpha 2 adrenergic receptor agonists identified using genetically altered mice and isobolographic analysis

“…Systemically administered moxonidine was also shown to inhibit Phase I and Phase II of the formalin response in rat with potency comparable to that of morphine (Shannon & Lutz, 2000). Like the aforementioned agonists, the binding affinity for moxonidine does not differ between the three receptor subtypes (A, B, C) (Piletz et al, 1996), lacking even a minor preference for one over the other two.…”