Cardiovascular drug reviews最新文献

{"title":"Pharmacology of the thromboxane receptor antagonist and thromboxane synthase inhibitor BM-531.","authors":"J. Dogné, S. Rolin, X. de Leval, P. Benoit, P. Neven, J. Delarge, P. Kolh, J. Damas, J. David, B. Masereel","doi":"10.1111/J.1527-3466.2001.TB00057.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00057.X","url":null,"abstract":"BM-531 (N-tert-butyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea), a torasemide derivative, is a novel noncarboxylic thromboxane receptor antagonist and thromboxane synthase inhibitor. Indeed, its affinity for human washed platelet TXA2 receptors labeled with [3H]SQ-29548 (IC50 = 0.0078 microM) is higher than sulotroban (IC50 = 0.93 microM) and SQ-29548 (IC50 = 0.021 microM). Moreover, BM-531 is characterized by a potent antiaggregatory property. Indeed, on one hand, in human citrated platelet-rich plasma BM-531 prevents platelet aggregation induced by arachidonic acid (600 microM) (ED100 = 0.125 microM), U-46619, a stable TXA2 agonist (1 microM) (ED50 = 0.482 microM) or collagen (1 microgram/mL) (percentage of inhibition: 42.9% at 10 microM) and inhibits the second wave of ADP (2 microM)-induced aggregation. On the other hand, when BM-531 is incubated in whole blood from healthy donors, the closure time measured by the recently developed platelet function analyser (PFA-100) is significantly prolonged. In addition, at the concentrations of 10 and 1 microM, BM-531 totally prevents the production of TXB2 by human platelets activated by arachidonic acid. Finally, at 10 microM, BM-531 significantly prevents rat fundus contractions induced by U-46619 but not by prostacyclin. These results suggest that BM-531, which is devoid of the diuretic property of torasemide, can be regarded as a promising antiplatelet agent.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79172190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ifetroban sodium: an effective TxA2/PGH2 receptor antagonist.","authors":"L. Rosenfeld, G. Grover, C. Stier","doi":"10.1111/J.1527-3466.2001.TB00058.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00058.X","url":null,"abstract":"This review presents a comprehensive discussion on the chemistry, pharmacokinetics, and pharmacodynamics of ifetroban sodium, a new thomboxane A2/prostaglandin H2 receptor antagonist. Thromboxane A2 is an arachidonic acid product, formed by the enzyme cyclooxygenase. In contrast to other cyclooxygenase products, thromboxane A2 has been shown to be involved in vascular contraction and has been implicated in platelet activation. In general, results of clinical studies and animal experiments indicate that hypertension is associated with hyperaggregability of platelets and increased thomboxane A2 levels in blood, urine, and tissues. The precursors to thromboxane A2, prostaglandin G2, and prostaglandin H2, also bind and activate the same receptors. Thus, a receptor antagonist was thought to be an improved strategy for reversing the actions of thromboxane A2/prostaglandin H2, rather than a thromboxane synthesis inhibitor. This review describes new methods for the synthesis and analysis of ifetroban, its tissue distribution, and its actions in a variety of animal models and disease states. We describe studies on the mechanisms of how ifetroban relaxes experimentally contracted isolated vascular tissue, and on the effects of ifetroban on myocardial ischemia, hypertension, stroke, thrombosis, and its effects on platelets. These experiments were conducted on several animal models, including dog, ferret, and rat, as well as on humans. Clinical studies are also described. These investigations show that ifetroban sodium is effective at reversing the effects of thromboxane A2- and prostaglandin H2-mediated processes.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74228654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake.","authors":"Yongge Liu, Y. Shakur, M. Yoshitake, J. Kambayashi","doi":"10.1111/J.1527-3466.2001.TB00076.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00076.X","url":null,"abstract":"Cilostazol (Pletal), a quinolinone derivative, has been approved in the U.S. for the treatment of symptoms of intermittent claudication (IC) since 1999 and for related indications since 1988 in Japan and other Asian countries. The vasodilatory and antiplatelet actions of cilostazol are due mainly to the inhibition of phosphodiesterase 3 (PDE3) and subsequent elevation of intracellular cAMP levels. Recent preclinical studies have demonstrated that cilostazol also possesses the ability to inhibit adenosine uptake, a property that may distinguish it from other PDE3 inhibitors, such as milrinone. Elevation of interstitial and circulating adenosine levels by cilostazol has been found to potentiate the cAMP-elevating effect of PDE3 inhibition in platelets and smooth muscle, thereby augmenting antiplatelet and vasodilatory effects of the drug. In contrast, elevation of interstitial adenosine by cilostazol in the heart has been shown to reduce increases in cAMP caused by the PDE3-inhibitory action of cilostazol, thus attenuating the cardiotonic effects. Cilostazol has also been reported to inhibit smooth muscle cell proliferation in vitro and has been demonstrated in a clinical study to favorably alter plasma lipids: to decrease triglyceride and to increase HDL-cholesterol levels. One, or a combination of several of these effects may contribute to the clinical benefits and safety of this drug in IC and other disease conditions secondary to atherosclerosis. In eight double-blind randomized placebo-controlled trials, cilostazol significantly increased maximal walking distance, or absolute claudication distance on a treadmill. In addition, cilostazol improved quality of life indices as assessed by patient questionnaire. One large randomized, double-blinded, placebo-controlled, multicenter competitor trial demonstrated the superiority of cilostazol over pentoxifylline, the only other drug approved for IC. Cilostazol has been generally well-tolerated, with the most common adverse events being headache, diarrhea, abnormal stools and dizziness. Studies involving off-label use of cilostazol for prevention of coronary thrombosis/restenosis and stroke recurrence have also recently been reported.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83064180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sixteenth annual meeting of the American Society for Hypertension, San Francisco, CA, USA, May 15-19, 2001.","authors":"A. Scriabine","doi":"10.1111/J.1527-3466.2001.TB00070.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00070.X","url":null,"abstract":"","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89375377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions.","authors":"Y. Tanaka, K. Shigenobu","doi":"10.1111/J.1527-3466.2001.TB00072.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00072.X","url":null,"abstract":"HNS-32 [N(1),N(1)-dimethyl-N(2)-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1- carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized azulene derivative. Computer simulation showed that its three dimensional structure is similar to that of the class Ib antiarrhythmic drugs, e.g., lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias induced by ischemia due to coronary ligation and/or ischemia-reperfusion in dogs and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative inotropic and chronotropic actions, prolonged atrial-His and His-ventricular conduction time and increased coronary blood flow. In the isolated guinea pig ventricular papillary muscle, HNS-32 decreased maximal rate of action potential upstroke (Vmax) and shortened action potential duration (APD). These findings suggest that HNS-32 inhibits inward Na+ and Ca2+ channel currents. In the isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca2+ channel-dependent and -independent contractions induced by a wide variety of chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated constriction of cerebral arteries. It is likely to block both, Na+ and Ca2+ channels expressed in cardiac and vascular smooth muscles. These multiple ion channel blocking effects are largely responsible for the antiarrhythmic and vasorelaxant actions of HNS-32. This drug may represent a novel approach to the treatment of arrhythmias.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86424362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of SR121463, a selective non-peptide vasopressin V2 receptor antagonist","authors":"C. S. Gal","doi":"10.1111/J.1527-3466.2001.TB00065.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00065.X","url":null,"abstract":"SR121463 is a selective, orally active, non-peptide antagonist of vasopressin (AVP) V 2 receptors with powerful aquaretic properties in various animal species and humans. SR121463 belongs to a new class of drugs, called aquaretics, which are capable of inducing free-water excretion without affecting electrolyte balance. SR121463 displays high affinity for animal and human V 2 receptors and exhibits a remarkably selective V 2 receptor profile. SR121463 and [ 3 H]SR121463 are used, therefore, as selective probes for characterization and labeling of V 2 receptors. In various functional studies in vitro, SR121463 behaves as a potent antagonist. It inhibits AVP-stimulated human renal adenylyl cyclase and dDAVP (1-desamino, 8-D arginine-vasopressin)-induced relaxation of rat aorta. SR121463 also behaves as an inverse agonist in cells expressing a constitutively activated human V 2 receptor mutant. In vitro, SR121463 rescued misfolded V 2 AVP receptor mutants by increasing cell surface expression and restoring V 2 function. In normally hydrated conscious rats, dogs and monkeys, SR121463, by either i.v. or p.o. administration, induced a dose-dependent aquaresis with no major changes in urinary Na + and K + excretion (unlike classical diuretics). In cirrhotic rats with ascites and impaired renal function, a 10-day treatment with SR121463 totally corrected hyponatremia and restored normal urine excretion. In a model of diabetic nephropathy in rats, SR121463 strongly reduced albumin excretion. SR121463 was also effective at extrarenal V 2 (or V 2 -like) receptors involved in vascular relaxation or clotting factor release in vitro and in vivo. In the rabbit model of ocular hypertension, SR121463 by either single or repeated instillation, decreased intraocular pressure. After acute and chronic administration to rats, dogs or healthy human volunteers, SR121463 was well absorbed and well tolerated. In all species studied the drug produced pronounced aquaresis without any agonist effect. Thus, SR121463 is a potent, orally active and selective antagonist at V 2 receptors with powerful aquaretic properties. It is a useful tool for further exploration of function of renal or extrarenal V 2 receptors. Pure V 2 receptor antagonists are likely to be therapeutically useful in several water-retaining diseases such as hyponatremia, Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH), congestive heart failure, liver cirrhosis, and other disorders possibly mediated by V 2 receptors (e.g., glaucoma).","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75877940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Growth Factor‐β:A Promising Target for Anti‐Stenosis Therapy","authors":"J. Chamberlain","doi":"10.1111/J.1527-3466.2001.TB00074.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00074.X","url":null,"abstract":"Transforming growth factor-beta (TGF-beta) is the general name for a family of cytokines which have widespread effects on many aspects of growth and development. The TGF-beta isoforms are produced by most cell types and exert a wide range of effects in a context-dependent autocrine, paracrine or endocrine fashion via interactions with distinct receptors on the cell surface. TGF-beta is involved in the wound healing process and, thus plays a significant role in the formation of a restenotic lesion after percutaneous transluminal coronary angioplasty (PTCA) or stenting. Perhaps because of its wide-ranging effects, TGF-beta is usually released from cells in a latent form, and its activation and signaling are complex. Manipulation of the TGF-beta1, TGF-beta2, and TGF-beta3 isoforms by inhibiting their expression, activation, or signaling reduces scarring and fibrosis in animal models. However, to date, few have reached clinical trial. This review summarizes current knowledge on the activation and signaling of TGF-beta, and focuses on the anti-TGF-beta strategies which may lead to clinical applications in the prevention of restenosis following PTCA or stenting.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80883093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xemilofiban/orbofiban: insight into drug development.","authors":"R. Anders, J. Kleiman, N. Nicholson, B. Wazowicz, D. Burns","doi":"10.1111/J.1527-3466.2001.TB00059.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00059.X","url":null,"abstract":"A number of studies have reported on the successful use of intravenous glycoprotein IIb/IIIa receptor antagonists in patients with unstable angina or undergoing percutaneous interventions. The promise of interrupting the aggregation of platelets in the setting of unstable plaques on a chronic basis had led to the evaluation of several oral agents for longer-term administration. The development program of two of these agents, xemilofiban and orbofiban, will be reviewed and evaluated to understand the selection process of therapeutic targets for use based upon complex pharmacokinetic and pharmacodynamic responses. A review of the pivotal phase III trial results will also be provided along with insights into the potential reasons for the lack of significant benefit shown with these agents to date.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81900067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacology of the ACAT inhibitor avasimibe (CI-1011).","authors":"Gemma Llaverías,&nbsp;Juan C Laguna,&nbsp;Marta Alegret","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration-dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B-containing lipoproteins into plasma. Avasimibe induced cholesterol 7alpha-hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol-fed as well as in non-cholesterol-fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non-HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50-500 mg/day, significantly reduced plasma total triglyceride and VLDL-cholesterol. Although total cholesterol, LDL-cholesterol, and HDL-cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol-lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.</p>","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22252929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue dedicated in memory of Dr. Edward H. Ahrens, Jr.","authors":"Edward H Ahrens","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This special issue of the \"Cardiovascular Drug Reviews\" is dedicated in memory of Dr. Edward H. Ahrens, Jr., who died on Dec. 9th, 2000 at the Princeton Medical Center in New Jersey at the age of 85. Dr. Ahrens was the Director of the Lipid Metabolism Laboratory at the Rockefeller University. Dr. Alexander Scriabine conceived the idea for the issue at the special memorial symposium held at the Rockefeller University on Feb. 05, 2002 under the auspices of The New York Lipid and Vascular Biology Research Club. Dr. Ahrens was the first president of the club. He started this club with Drs. Howard Eder and DeWitt Goodman. Dr. Eder thought that it would be a fitting attribute to honor one of the founding fathers of the club by hosting a memorial symposium. I, as the President of the club for that academic year, had no hesitation in accepting the proposal. This year will be the 40th anniversary of the club and its continued success provides a glimpse of the fine legacy left behind by Dr. Ahrens. Dr. Ahrens also played a pivotal role in the establishment of the Journal of Lipid Research. This is the 43rd year of the journal and in this commemorative issue we are reproducing a review he wrote for the 25th anniversary of the journal. I was never personally acquainted with Dr. Ahrens. However, I am honored that I got this opportunity to pay tribute to a great scientist whose work has contributed immensely to the progress of lipid research. He was a person who touched many lives and still continues to do so. My involvement in the remembrance of Dr. Ahrens shows that science not only impacts your contemporaries but also generations that follow you. Scientific research is a journey where you can leave your trails behind and be remembered for your work long after your departure from this world. Dr. Ahrens contributed immensely to the understanding of cholesterol metabolism. In the early stages of his career he showed that phospholipids solubilize fat in the blood. Now we know that a monolayer of phospholipids surrounds the neutral lipid core of cholesterol esters and triglycerides in lipoproteins. This monolayer contains proteins, called apolipoproteins, which play a major role in lipoprotein catabolism. Lipoproteins are the major vehicles that transport triglycerides and cholesterol in the plasma. He also described a new form of primary biliary cirrhosis characterized by the presence of xanthomas and hyperlipidemia with normal translucent plasma. Subsequently, his group at the Rockefeller Institute developed methods for the separation of lipids using silicic acid columns, isolated highly unsaturated long chain fish oil fatty acids using gas-liquid chromatography, standardized techniques to study sterol metabolism, and introduced the concept of using beta-sitosterolemia as an internal marker for cholesterol balance studies. These studies revealed that individuals show a reproducible response to a given regimen when studied over time. In contrast, differen","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22155428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}