Document Detail


Development and therapeutic indications of orally-active non-peptide vasopressin receptor antagonists.
MedLine Citation:
PMID:  11322860     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vasopressin (AVP) is a cyclic nonapeptide hormone that exhibits many physiological effects including free water reabsorption, vasoconstriction, cellular proliferation and adrenocorticotrophic hormone (ACTH) secretion. In a healthy organism, AVP plays an important role in the homeostasis of fluid osmolality and volume status. However, in several diseases or conditions such as the syndrome of inappropriate secretion of AVP (SIADH), congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome, dysmenorrhoea and ocular hypertension, AVP may play an important role in their pathophysiology. Recently, orally-active non-peptide AVP receptor antagonists were developed by random screening of chemical entities and optimisation of lead compounds. These include agents specific for the V(1)-vascular and V(2)-renal AVP receptor subtypes. Dual V(1)/V(2) AVP receptor antagonists are also being studied. Some of these non-peptide receptor antagonists have been studied extensively, while others are currently under investigation. Potential therapeutic indications for AVP receptor antagonists comprise: 1) The blockade of V(1)-vascular AVP receptors in arterial hypertension, congestive heart failure, Raynaud's syndrome, peripheral vascular disease and dysmenorrhea. 2) The blockade of V(2)-renal AVP receptors in the syndrome of inappropriate secretion of vasopressin, congestive hart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatraemia. 3) The blockade of V(3)-pituitary AVP receptors in ACTH-secreting tumours. This review examines the pharmacology of orally-active non-peptide AVP receptor antagonists and their clinical applications.
Authors:
S B Paranjape; M Thibonnier
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  10     ISSN:  1354-3784     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-04-27     Completed Date:  2001-08-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  825-34     Citation Subset:  IM    
Affiliation:
Case Western Reserve University School of Medicine and University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, Ohio 44106-4951, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Diabetes Insipidus / drug therapy
Dysmenorrhea / drug therapy
Female
Heart Failure / drug therapy
Humans
Hypertension / drug therapy
Hyponatremia / drug therapy
Receptors, Vasopressin / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Receptors, Vasopressin

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


Previous Document:  Novel therapeutics for the treatment of paediatric pulmonary arterial hypertension.
Next Document:  Therapeutic potential of Na-H exchange inhibitors for the treatment of heart failure.