Document Detail


Moxonidine: a new antiadrenergic antihypertensive agent.
MedLine Citation:
PMID:  10489098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Moxonidine is a centrally acting antihypertensive. Its action is mediated by imidazoline I1 receptors located in the rostral ventro-lateral medulla (RVLM). Animal experiments show that much smaller amounts are required to reduce blood pressure (BP) when it is given intracisternally, or injected directly into the RVLM, compared to intravenous dose. Pretreatment with imidazoline I1 blockade from efaroxan abolishes the antihypertensive action of microinjection of moxonidine into the RVLM in the spontaneously hypertensive rat (SHR), while alpha2 blockade from SKF 86466 is much less effective. Microinjection of efaroxan into the RVLM prevents the fall of BP in the SHR from intravenous moxonidine. Moxonidine binds with an affinity for the imidazoline I1 receptor that is 33 times more effective than is alpha2-receptor binding. There is only a few fold preference for binding at the imidazoline I1-receptor for clonidine. Moxonidine results in a fall in adrenaline, noradrenaline and renin levels in humans, as might be expected from central inhibition of sympathetic tone. Moxonidine gives a fall of BP due to a decline in systemic vascular resistance, while the heart rate, cardiac output, stroke volume and pulmonary artery pressures are not affected. There is a reduction in left-ventricular end systolic and diastolic volumes. There is a regression of left-ventricular hypertrophy after moxonidine was given for 6 months. Following oral administration the half-life (Tmax) is about 1 h. Moxonidine is highly bioavailable, approaching 90%. Moxonidine is largely excreted unchanged, biotransformation is unimportant. It has a T(1/2) of 2.5 h, renal insufficiency prolongs the T(1/2). However, suggesting possible retention in the central nervous system (CNS) the antihypertensive effect lasts longer than would be expected from the half-life. Moxonidine has been shown to be suitable for administration once daily. Moxonidine is an effective antihypertensive drug. In the course of its evaluation it has been compared with representatives from each important class of antihypertensive drugs, with diuretics, both alpha- and beta-blocking drugs, clonidine, calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors. These studies have shown that BP control is overall similar with moxonidine and these other agents. Moxonidine has a favourable side-effect profile, at least in part due to its lack of effect on central alpha2 receptors.
Authors:
B N Prichard; B R Graham; C W Owens
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of hypertension. Supplement : official journal of the International Society of Hypertension     Volume:  17     ISSN:  0952-1178     ISO Abbreviation:  J Hypertens Suppl     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-11-02     Completed Date:  1999-11-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8501422     Medline TA:  J Hypertens Suppl     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  S41-54     Citation Subset:  IM    
Affiliation:
Centre of Clinical Pharmacology, University College London, UK.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Antagonists / therapeutic use*
Animals
Antihypertensive Agents / therapeutic use*
Blood Pressure / drug effects
Humans
Hypertension / drug therapy*,  metabolism,  physiopathology
Imidazoles / therapeutic use*
Imidazoline Receptors
Receptors, Adrenergic, alpha-2 / antagonists & inhibitors*,  metabolism
Receptors, Drug / agonists
Sympathetic Nervous System / drug effects,  metabolism
Treatment Outcome
Chemical
Reg. No./Substance:
0/Adrenergic Antagonists; 0/Antihypertensive Agents; 0/Imidazoles; 0/Imidazoline Receptors; 0/Receptors, Adrenergic, alpha-2; 0/Receptors, Drug; 75438-57-2/moxonidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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