Mechanism of Action

The antihypertensive activity of clonidine can be ascribed solely to a decrease in the sympathetic activity transmitted from the brain to the peripheral vasculature. After clonidine administration, direct measurements of sympathetic nerve activity show that electrical discharge is reduced in a number of sympathetic nerves, including the cardiac, splanchnic, and cervical nerves.

It is generally agreed that clonidine acts in the same general area in the brain as does a-methyldopa, that is, somewhere in the medulla oblongata. The principal difference between clonidine and a-methyldopa is that clonidine acts directly on a2-receptors, whereas a-methyldopa first must be converted by synthetic enzymes to a-methylnorepinephrine.

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