Cardiovascular drug reviews最新文献

{"title":"Sotalol: the mechanism of its antiarrhythmic-defibrillating effect.","authors":"M. Manoach,, N. Tribulova","doi":"10.1111/J.1527-3466.2001.TB00062.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00062.X","url":null,"abstract":"This minireview deals with the role of intercellular communication and synchronization in the initiation and maintenance of ventricular fibrillation. It is proposed that myocardial cell junctions might represent a therapeutic substrate for the prevention of this fatal arrhythmia. This hypothesis is supported by the results of recent experimental studies involving elucidation of the mechanism of antiarrhythmic-defibrillating effects of sotalol. Enhancement of intercellular communication and myocardial synchronization are thought to play critical role in the mechanism of action of this drug.","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":"76278329","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":"Carvedilol: molecular and cellular basis for its multifaceted therapeutic potential.","authors":"Jianhua Cheng, K. Kamiya, Itsuo Kodama","doi":"10.1111/J.1527-3466.2001.TB00061.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00061.X","url":null,"abstract":"Carvedilol is a unique cardiovascular drug of multifaceted therapeutic potential. Its major molecular targets recognized to date are membrane adrenoceptors (beta 1, beta 2, and alpha 1), reactive oxygen species, and ion channels (K+ and Ca2+). Carvedilol provides prominent hemodynamic benefits mainly through a balanced adrenoceptor blockade, which causes a reduction in cardiac work in association with peripheral vasodilation. This drug assures remarkable cardiovascular protection through its antiproliferative/atherogenic, antiischemic, antihypertrophic, and antiarrhythmic actions. These actions are a consequence of its potent antioxidant effects, amelioration of glucose/lipid metabolism, modulation of neurohumoral factors, and modulation of cardiac electrophysiologic properties. The usefulness of carvedilol in the treatment of hypertension, ischemic heart disease, and congestive heart failure is based on a combination of hemodynamic benefits and cardiovascular protection.","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":"85144429","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":"Norbormide: a calcium entry blocker with selective vasoconstrictor activity in rat peripheral arteries.","authors":"S. Bova, L. Cima, V. Golovina, S. Luciani, G. Cargnelli","doi":"10.1111/J.1527-3466.2001.TB00067.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00067.X","url":null,"abstract":"Norbormide is a unique vasoactive substance endowed with species- and tissue-specific, endothelium independent, vasoconstrictor activity that is restricted to the peripheral arteries of rat. In rat aorta and in all tested arteries of other species norbormide exhibits vasorelaxant property presumably due to the blockade of calcium channels. A calcium entry blocker effect of norbormide has also been described in isolated, perfused guinea pig hearts. In these preparations norbormide produced coronary vasodilator, as well as negative inotropic and dromotropic effects. In single ventricular myocytes of guinea pigs norbormide reduces L-type calcium current. The mechanism underlying the selective vasoconstrictor effect of norbormide is unknown. In rat caudal artery, a vessel contracted by norbormide, the drug activates phospholipase C (PLC) signal cascade which is the biochemical pathway involved in the contractile effect triggered by most receptor-activating vasoactive agents. Therefore, norbormide-induced contraction of rat peripheral vessels is likely to be due to the activation of a PLC-coupled receptor abundantly or selectively expressed in vascular smooth muscle cells. The identification of this putative receptor could facilitate the development of tissue-selective pharmacological agents.","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":"85925653","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":"G. Llaverías, J. Laguna, M. Alegret","doi":"10.1111/J.1527-3466.2003.TB00104.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2003.TB00104.X","url":null,"abstract":"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.","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":"88191558","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":"Eplerenone: a selective aldosterone receptor antagonist (SARA).","authors":"J. Delyani, R. Rocha, C. Cook, D. Tolbert, S. Levin, B. Roniker, D. Workman, Yuen-lung L. Sing, Brian Whelihan","doi":"10.1111/J.1527-3466.2001.TB00064.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00064.X","url":null,"abstract":"Aldosterone, the final product of the renin-angiotensin-aldosterone system (RAAS), is a mineralocorticoid hormone that classically acts, via the mineralocorticoid (aldosterone) receptor, on epithelia of the kidneys, colon, and sweat glands to maintain electrolyte homeostasis. Aldosterone has also been shown to act at nonepithelial sites where it can contribute to cardiovascular disease such as hypertension, stroke, malignant nephrosclerosis, cardiac fibrosis, ventricular hypertrophy, and myocardial necrosis. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin type 1 (AT(1)) receptor antagonists act to suppress the RAAS, these agents do not adequately control plasma aldosterone levels--a phenomenon termed \"aldosterone synthesis escape.\" Spironolactone, a nonselective aldosterone receptor antagonist, is an effective agent to suppress the actions of aldosterone; its use is, however, associated with progestational and antiandrogenic side effects due to its promiscuous binding to other steroid receptors. For these reasons, eplerenone--the first agent of a new class of drugs known as the selective aldosterone receptor antagonists (SARAs)--is under development. In rodent models, eplerenone provides marked protection against vascular injury in the kidney and heart. In phase II clinical trials, eplerenone demonstrates 24-h control of blood pressure with once or twice daily dosing, and is safe and well tolerated in patients with heart failure when given with standard of care agents. Pharmacokinetic studies reveal that eplerenone has good bioavailability with low protein binding, good plasma exposure, and is highly metabolized to inactive metabolites and excreted principally in the bile. Eplerenone is well tolerated in acute and chronic safety pharmacology studies. Ongoing phase III trials of eplerenone in the treatment of hypertension and heart failure are underway. These studies will extend our understanding of selective aldosterone receptor antagonism in the treatment of chronic cardiovascular disease.","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":"74692618","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":"Multilateral in vivo and in vitro protective effects of the novel heat shock protein coinducer, bimoclomol: results of preclinical studies.","authors":"P. Nanasi, Andrea Jednakovits","doi":"10.1111/J.1527-3466.2001.TB00060.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00060.X","url":null,"abstract":"Bimoclomol, the recently developed non-toxic heat shock protein (HSP) coinducer, was shown to display multilateral protective activities against various forms of stress or injuries at the level of the cell, tissue or organism. The compound enhanced the transcription, translation and expression of the 70 kD heat shock protein (HSP-70) in myogenic and HeLa cell lines exposed to heat stress, and increased cell survival on exposure to otherwise lethal thermal injury. Bimoclomol increased contractility of the working mammalian heart, this effect was associated with the increased intracellular calcium transients due to increased probability of opening of ryanodine receptors in the sarcoplasmic reticulum (SR). In healthy tissues these cardiac effects were evident only at relatively high concentrations of the drug, while in the ischemic myocardium bimoclomol exerted significant cardioprotective and antiarrhythmic effects at submicromolar concentrations. It decreased ischemia-induced reduction of contractility and of cardiac output, and dramatically decreased the elevation of the ST-segment during ischemia as well as the occurrence of ventricular fibrillation upon reperfusion. Bimoclomol was also active in various pathological animal models subjected to acute or chronic stress. In the spontaneously hypertensive rats chronic pretreatment with bimoclomol restored sensitivity of aortic rings to acetylcholine; this effect was accompanied by accumulation of HSP-70 in the tissues. Bimoclomol pretreatment significantly diminished the consequences of vascular disorders associated with diabetes mellitus. Diabetic neuropathy, retinopathy, and nephropathy were prevented or diminished, while wound healing was enhanced by bimoclomol. Enhancement of wound healing by bimoclomol was observed after thermal injury as well as following ultraviolet (UV) irradiation. In addition to the beneficial effects on peripheral angiopathies, bimoclomol antagonized the increase in permeability of blood-brain barrier induced by subarachnoid hemorrhager or arachidonic acid. A general and very important feature of the above effects of bimoclomol was that the drug failed to cause alterations under physiological conditions (except the enhanced calcium release from cardiac sarcoplasmic reticulum). Bimoclomol was effective only under conditions of stress. Consistent with its HSP-coinducer property, bimoclomol alone had very little effect on HSP production. Its protective activity became apparent only in the presence of cell damage. Currently, bimoclomol reached the end of the Phase II clinical trial in a group of 410 patients with diabetic complications. Results of this trial will answer the question, whether a compound with promising in vitro and in vivo preclinical findings will produce the anticipated beneficial effects in humans. In the event of a positive outcome of this trial, the indications for bimoclomol will be substantially extended.","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":"81222937","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":"Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall.","authors":"Y. Kishi, S. Ohta, N. Kasuya, Shinya Sakita, T. Ashikaga, M. Isobe","doi":"10.1111/J.1527-3466.2001.TB00066.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00066.X","url":null,"abstract":"Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.","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":"82050884","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":"AH-1058: a novel cardioselective Ca2+ channel blocker.","authors":"A. Takahara, A. Sugiyama, R. Yoshimoto, K. Hashimoto","doi":"10.1111/J.1527-3466.2001.TB00071.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00071.X","url":null,"abstract":"The pharmacologic profile of a cyproheptadine-related compound, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride (AH-1058), was assessed in various in vivo and in vitro models. In guinea pig cardiomyocytes, AH-1058 effectively suppressed L-type Ca2+ channel currents without affecting other ion channel or ion exchange currents. In rat cerebral cortical membranes AH-1058 appears to bind preferentially to L-type Ca2+ channels at phenylalkylamine- and benzothiazepine-binding sites. In canine isolated, blood-perfused heart preparations, AH-1058 exerted negative inotropic, dromotropic, and chronotropic and weak coronary vasodilator effects. In halothane-anesthetized dogs, AH-1058 suppressed ventricular contractility and decreased blood pressure and cardiac output. Total peripheral vascular resistance was hardly affected by the drug, suggesting that in vivo AH-1058 can selectively suppress cardiac, as compared to peripheral vascular, function. In conscious dogs, by intravenous administration AH-1058 reduced systolic blood pressure and maximal upstroke velocity of the left ventricular pressure, while it increased heart rate in a dose-dependent manner. The drug did not affect diastolic blood pressure, which is quite different from cardiovascular properties of well-known Ca2+ channel blockers, verapamil and diltiazem. This unique cardiovascular profile of AH-1058 is expected to be useful in the treatment of certain pathological processes such as the obstructive hypertrophic cardiomyopathy, vasovagal syncope, dissecting aortic aneurysm, and ventricular arrhythmias, in which selective inhibition of the ventricular Ca2+ channels is essential for drug therapy.","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":"90875061","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":"Cardiovascular properties of yangambin, a lignan isolated from Brazilian plants.","authors":"E. Tibiriçá","doi":"10.1111/J.1527-3466.2001.TB00073.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00073.X","url":null,"abstract":"Yangambin was initially selected from a number of lignans isolated from Brazilian plants for its ability to antagonize Platelet-Activating Factor (PAF, 1-O-hexadecyl-2-acetyl- sn-glyceryl-3-phosphorylcholine)-induced biological effects. Subsequently it was shown that, besides its antagonistic properties at PAF receptors, yangambin also prevents the cardiovascular collapse observed during anaphylactic and endotoxic/septic shocks, as well as the vascular and cardiac hyporesponsiveness to catecholamines in endotoxic shock. It is suggested that this naturally occurring compound could be of potential interest in the adjunctive management of the above mentioned pathologies. In the present article, we review the main studies investigating the pharmacological properties of yangambin related to the cardiovascular function.","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":"78857661","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":"Gene transfer therapy in vascular diseases.","authors":"M. McKay, M. Gaballa","doi":"10.1111/J.1527-3466.2001.TB00069.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00069.X","url":null,"abstract":"Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of angiogenesis in the cardiac muscle are discussed in reviews by several investigators (13,26,57,74,83). In another review, Meyerson et al. (43) discuss advances in gene therapy for vascular proliferative disorders and chronic peripheral and cardiac ischemia.","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":"79010564","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}