Linked Life Data

17204748

Source:http://linkedlifedata.com/resource/pubmed/id/17204748

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-3-19
pubmed:abstractText
Elevated lipolysis and circulating free fatty acid (FFA) levels have been linked to the pathogenesis of insulin resistance. A1 adenosine receptor agonists are potent inhibitors of lipolysis. Several A1 agonists have been tested as potential antilipolytic agents; however, their effect on the cardiovascular system remains a potential problem for development of these agents as drugs. In the present study, we report that CVT-3619 [(2-{6-[((1R,2R)-2-hydroxycyclopentyl) amino] purin9-yl} (4S,5 S,2R,3R)5-[(2fluorophenylthio) methyl] oxolane-3,4-diol)], a novel partial A1 receptor agonist, significantly reduces circulating FFA levels without any effect on heart rate and blood pressure in awake rats. Rats were implanted with indwelling arterial and venous cannulas to obtain serial blood samples, record arterial pressure, and administer drug. CVT-3619 decreased FFA levels in a dose-dependent manner at doses from 1 up to 10 mg/kg. The FFA-lowering effect was blocked by the A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine. Triglyceride (TG) levels were also significantly reduced by CVT-3619 treatment in the absence and presence of Triton. Tachyphylaxis of the antilipolytic effect of CVT-3619 (1 mg/kg i.v. bolus) was not observed with three consecutive treatments. An acute reduction of FFA by CVT-3619 was not followed by a rebound increase of FFA as seen with nicotinic acid. The potency of insulin to decrease lipolysis was increased 4-fold (p < 0.01) in the presence of CVT-3619 (0.5 mg/kg). In summary, CVT-3619 is an orally bioavailable A1 agonist that lowers circulating FFA and TG levels by inhibiting lipolysis. CVT-3619 has antilipolytic effects at doses that do not elicit cardiovascular effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
321
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-33
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17204748-Adenosine, pubmed-meshheading:17204748-Adenosine A1 Receptor Agonists, pubmed-meshheading:17204748-Adipocytes, pubmed-meshheading:17204748-Animals, pubmed-meshheading:17204748-Blood Pressure, pubmed-meshheading:17204748-Cell Separation, pubmed-meshheading:17204748-Dose-Response Relationship, Drug, pubmed-meshheading:17204748-Fatty Acids, Nonesterified, pubmed-meshheading:17204748-Heart Rate, pubmed-meshheading:17204748-Hypoglycemic Agents, pubmed-meshheading:17204748-Insulin, pubmed-meshheading:17204748-Insulin Resistance, pubmed-meshheading:17204748-Lipolysis, pubmed-meshheading:17204748-Male, pubmed-meshheading:17204748-Niacin, pubmed-meshheading:17204748-Polyethylene Glycols, pubmed-meshheading:17204748-Rats, pubmed-meshheading:17204748-Rats, Sprague-Dawley, pubmed-meshheading:17204748-Triglycerides
pubmed:year
2007
pubmed:articleTitle
Antilipolytic activity of a novel partial A1 adenosine receptor agonist devoid of cardiovascular effects: comparison with nicotinic acid.
pubmed:affiliation
Department of Pharmacology, CV Therapeutics, Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA. arvinder.dhalla@cvt.com
pubmed:publicationType
Journal Article, Comparative Study, In Vitro