• Central sympatholytic drugs reduce blood pressure mainly by stimulating central α(2) -adrenergic receptors in the brainstem centers, thereby reducing sympathetic nerve activity and neuronal release of norepinephrine to the heart and peripheral circulation. • This class of drugs, however, is currently used mainly as fourth-line (or beyond) drug therapy for hypertension because of side effects of drowsiness, fatigue, and dry mouth. • Rebound hypertension is also another major concern in certain drugs with a short half-life, particularly in patients who are nonadherent to the regimen. Therefore, their use on a "PRN" basis for treatment of blood pressure surge in the absence of symptoms or acute target complications should also be avoided.