Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Clonidine, guanfacine, guanabenz and alpha-methyl-dioxyphenylalanine (DOPA), the prototypes of centrally acting antihypertensives, are assumed to induce peripheral sympathoinhibition and a reduction in blood pressure via the stimulation of alpha2-adrenoceptors in the brain stem. More recently, central imidazoline (I1)-receptors have been recognized to be another target of centrally acting antihypertensive drugs. Clonidine is considered to be a mixed agonist that stimulates both alpha2- and I1-receptors. Moxonidine and rilmenidine are considered to be moderately selective I1-receptor stimulants, although it still remains unknown whether these agents act directly on the receptor as genuine agonists. A survey is given on the location, characteristics and functional aspects of imidazoline I1-receptors as targets of centrally acting antihypertensives. Furthermore, the pharmacology and clinical potential of selective I1-receptor agonists such as moxonidine and rilmenidine are discussed. Although far from perfect, these compounds have shown that it may potentially be possible to develop agents with which the well-known side effects caused by alpha2-receptor agonists can be separated from the central antihypertensive mechanism.