Clonidine hydrochloride (Catapres) is a centrally active α-adrenergic agonist used predominantly as an antihypertensive agent.

Clonidine, at concentrations of 0.01, 0.1, or 1 μM, significantly elevates CGRP (α and β) mRNA expression in endothelial cells in a dose-dependent manner. Additionally, a 24-hour treatment with 1 μM clonidine notably augments NO levels in these cells. This indicates that the NO pathway plays a crucial role in modulating the clonidine-induced CGRP production[2].

Administered intraperitoneally at a dose of 50 μg/kg, clonidine markedly reduces rat body temperature, peaking at 1 hour and persisting for 3 hours; this effect is notably counteracted by a pre-administration of phentolamine into the cerebral ventricles[1]. Additionally, clonidine (0.003-0.05 mg/kg, i.p.) effectively inhibits PCP-induced dopamine release in the prefrontal cortex, an effect that is blocked by the alpha-2A receptor antagonist BRL-44408[3]. In normotensive rats treated with DMSO, clonidine (0.6 μg intracisternally) does not alter blood pressure, but following central adenosine A1R inhibition with DPCPX, it significantly lowers blood pressure. Conversely, in DMSO-treated aortic-banded rats, clonidine prominently decreases blood pressure, a response that remains unchanged after DPCPX pretreatment. Additionally, in SO rats with central A1R blockage, clonidine not only reduces blood pressure but also significantly elevates pERK1/2 levels in the RVLM, an effect not observed in DMSO-pretreated SO rats. Similarly, clonidine boosts RVLM pERK1/2 levels in vehicle-treated aortic-banded rats, unaffected by DPCPX[4].