Effects of moxonidine, an imidazoline antihypertensive agent, on second messenger systems in rat brain

Moxonidine, an imidazoline, binds to alpha 2-adrenoceptors and imidazoline receptors. We sought to determine the effects of moxonidine on accumulation of cAMP, cGMP, and phosphoinositide turnover in minislices of cerebral cortex and brainstem. In cerebral cortex, but not in brainstem, moxonidine inhibited the stimulated production of cAMP, an effect blocked by alpha 2-adrenergic antagonist rauwolscine. It also increased the hydrolysis of phosphoinositide above 100 microM in cerebral cortex and failed to alter accumulation of cGMP in both regions. We conclude that moxonidine is a typical alpha 2-adrenergic agonist inhibiting cAMP production in cerebral cortex, but not in brainstem, its interaction with I1 imidazoline sites in brainstem did not regulate second messenger systems, and moxonidine increased phosphoinositide turnover in cerebral cortex by unknown mechanisms.