title: Centrally acting antihypertensive drugs. Present and future.
abstract: The classic centrally acting antihypertensives such as clonidine, guanfacine and alpha-methyl-DOPA (via its active metabolite alpha-methyl-noradrenaline) induce peripheral sympathoinhibition and a fall in blood pressure as a result of alpha2-adrenoceptor stimulation in the brain stem. These drugs have lost much of their clinical importance because of their unfavourable side-effects (sedation, dry mouth, impotence), which are also mediated by alpha2-adrenoceptors, although in other anatomical regions. Moxonidine and rilmenidine are the examples of a new class of centrally acting antihypertensives, which cause peripheral sympathoinhibition mediated by imidazoline (I1)-receptors in the rostral ventromedulla (RVLM). Their side-effect profile appears to be better than that of clonidine and alpha-methyl-DOPA, probably because of a weaker affinity for alpha2-adrenoceptors. The mode of action, haemodynamic profile, antihypertensive efficacy and adverse reactions of the classic and newer centrally acting antihypertensives are the subject of the present survey. Attention is also paid to other therapeutic applications of centrally acting antihypertensives, such as congestive heart failure and the metabolic syndrome.
authors.affiliation: Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012469:Salivary Glands / Q000187:drug effects; D013997:Time Factors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000959:Antihypertensive Agents; D007093:Imidazoles; C043482:moxonidine