Document Detail


Neurohumoral response to carmoxirole, a selective dopamine (D2) receptor agonist, in patients with chronic moderate heart failure.
MedLine Citation:
PMID:  9825185     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neurohormonal activation and elevated ventricular filling pressures are prominent features in heart failure. Carmoxirole is a DA2 receptor agonist with limited central activity that modulates sympathetic activation and subsequently reduces pre-load and afterload in animals. The effect of carmoxirole on neurohormones and hemodynamics in humans was evaluated in 12 normotensive patients with NYHA class III-IV heart failure on stable ACE 1 and diuretic therapy. Carmoxirole (0.25-1.00 mg) was administered on 2 consecutive days, and hemodynamic and neurohormonal measurements were carried out. Values given are maximal percent changes from prestudy baseline (significance level P < 0.05). The lower dose on day 1 (0.25-0.50 mg) reduced circulating norepinephrine, vasopressin, and ANP by 40%, 19%, and 25%, respectively. In addition, on day 2, at a dose level of 0.75-1.00 mg, plasma renin activity decreased by 30%. Mean arterial pressure and systemic vascular resistance were reduced by 10% and 18%, and pulmonary wedge and right atrial pressure by 38% and 39%, respectively. Cardiac index improved by 20%. Despite a concomitant 12% reduction in heart rate, both stroke volume and stroke work index increased by 32% and 31%, respectively. Mean pulmonary artery pressure decreased by 21%, whereas pulmonary resistance was not affected. Thus, carmoxirole modulates sympathetic activation, accompanied by changes in vasopressin and ANP, and the renin-angiotensin system at higher dosages. These effects lead to a reduction in systemic resistance and heart rate, and an improvement in cardiac pump function and left and right ventricular filling pressures. It is concluded that carmoxirole induces beneficial effects on hemodynamic and neurohumoral parameters in heart failure.
Authors:
M van der Ent; A F van den Heuvel; W J Remme
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  12     ISSN:  0920-3206     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1999-03-02     Completed Date:  1999-03-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  387-94     Citation Subset:  IM    
Affiliation:
Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Aged
Atrial Natriuretic Factor / drug effects
Blood Pressure / drug effects
Cardiac Output / drug effects
Chronic Disease
Dopamine Agonists / pharmacology*
Electrocardiography
Female
Heart Failure / physiopathology*
Heart Rate / drug effects
Humans
Indoles / pharmacology*
Male
Neurotransmitter Agents / physiology*
Norepinephrine / metabolism
Pulmonary Wedge Pressure / drug effects
Pyridines / pharmacology*
Receptors, Dopamine D2 / agonists*
Vasopressins / drug effects
Chemical
Reg. No./Substance:
0/Dopamine Agonists; 0/Indoles; 0/Neurotransmitter Agents; 0/Pyridines; 0/Receptors, Dopamine D2; 11000-17-2/Vasopressins; 51-41-2/Norepinephrine; 85637-73-6/Atrial Natriuretic Factor; 98323-83-2/carmoxirole

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


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