Document Detail

RWJ 26629, a new potassium channel opener and vascular smooth muscle relaxant: a potential antihypertensive and antianginal agent.
MedLine Citation:
PMID:  8246137     Owner:  NLM     Status:  MEDLINE    
The effects of trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-7-(2-oxopiperidin -1-yl)-7H- thieno[3,2-b]pyran (RWJ 26629) were compared with those of the standard potassium channel opener cromakalim and several standard calcium channel blockers. RWJ 26629 lowered the mean arterial blood pressure in conscious spontaneously hypertensive (ED30 = 10 micrograms/kg p.o. or 8 micrograms/kg i.v.) and renal hypertensive (15 micrograms/kg p.o.) rats, conscious renal hypertensive (ED20 = 4 micrograms/kg p.o.) and normotensive (ED20 = 5 micrograms/kg p.o. or 2 micrograms/kg i.v.) dogs and anesthetized rhesus monkeys (ED20 = 6 micrograms/kg i.v.). RWJ 26629 was more potent than cromakalim and had a maximal activity greater than the calcium channel blockers. At antihypertensive doses, RWJ 26629 had no significant effect on cardiac force, cardiac output, stroke volume or stroke work in dogs and had little or no effect on renal, carotid or femoral blood flow or vascular resistance. RWJ 26629 was also selective for antihypertensive activity in rats compared with its ability to inhibit intestinal motility. However, RWJ 26629 did relax contracted pulmonary smooth muscle in vivo at antihypertensive doses. All compounds tested caused reflex tachycardia in conscious dogs, although this effect was lowest for RWJ 26629. Most importantly, RWJ 26629 potently and selectively increased coronary blood flow with a potency and duration of action greater than that of cromakalim or nifedipine without affecting contractile force. In vitro, RWJ 26629 selectively relaxed precontracted coronary arteries compared with its effect on femoral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
L B Katz; E C Giardino; J J Salata; J B Moore; R Falotico
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  267     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1994-01-06     Completed Date:  1994-01-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  648-56     Citation Subset:  IM    
Research Laboratories, R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey.
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MeSH Terms
Angina Pectoris / drug therapy
Antihypertensive Agents / pharmacology*
Benzopyrans / pharmacology
Bronchoconstriction / drug effects
Calcium Channel Blockers / pharmacology
Dose-Response Relationship, Drug
Gastrointestinal Motility / drug effects
Guinea Pigs
Heart Atria / drug effects
Macaca mulatta
Mice, Inbred Strains
Muscle Relaxation / drug effects*
Muscle, Smooth, Vascular / drug effects*,  physiology
Nitrendipine / metabolism
Papillary Muscles / drug effects
Pilocarpine / pharmacology
Potassium Channels / drug effects*
Pyrans / pharmacology*
Pyrroles / pharmacology
Rats, Inbred SHR
Rats, Sprague-Dawley
Rubidium / pharmacokinetics
Rubidium Radioisotopes / diagnostic use
Thiophenes / pharmacology*
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Antihypertensive Agents; 0/Benzopyrans; 0/Calcium Channel Blockers; 0/Potassium Channels; 0/Pyrans; 0/Pyrroles; 0/Rubidium Radioisotopes; 0/Thiophenes; 0/Vasodilator Agents; 144319-31-3/RWJ 26629; 39562-70-4/Nitrendipine; 7440-17-7/Rubidium; 92-13-7/Pilocarpine; 94470-67-4/Cromakalim

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

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