Pub Date : 2007-04-02DOI: 10.1111/J.1527-3466.1987.TB00512.X
J. Kyncl, S. Buckner, J. Debernardis, M. Winn, H. Brondyk, R. Dudley
{"title":"Abbott-57219[SCH-40054]: A Novel Nasal Decongestant","authors":"J. Kyncl, S. Buckner, J. Debernardis, M. Winn, H. Brondyk, R. Dudley","doi":"10.1111/J.1527-3466.1987.TB00512.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.1987.TB00512.X","url":null,"abstract":"","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86072529","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}
Pub Date : 2007-04-02DOI: 10.1111/J.1527-3466.1987.TB00508.X
Günter Scholtysik, Peter Rüegg
{"title":"DPI 201-106","authors":"Günter Scholtysik, Peter Rüegg","doi":"10.1111/J.1527-3466.1987.TB00508.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.1987.TB00508.X","url":null,"abstract":"","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88477147","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}
Pub Date : 2006-06-09DOI: 10.1111/J.1527-3466.2001.TB00184.X
M. Cooper, R. Webb, M. de Gasparo
This review deals with similarities and differences between the effects of ACE inhibitors and AT1-receptor blockers in the kidney. Specific receptor blockade has demonstrated that the beneficial effects of AT1 blockers arise from two mechanisms: the reduction of the AT1 receptor mediated response and the increase in plasma levels of Ang II through the AT1-receptor blockade, which leads to increased stimulation of the AT2 receptor (the so-called yin-yang effect). Both ACE inhibition and AT1-receptor blockade provide significant renal protection in the majority of experimental animal models of kidney diseases. AT1 receptor blockade may offer additional clinical benefits over ACE inhibitor treatment, particularly in the kidney, where AT1-receptor blockade does not cause the fall in glomerular filtration rate seen with ACE inhibitor treatment. A number of long-term clinical studies currently running should show the real value of this new class of compounds in the management of hypertension and associated cardiorenal diseases.
{"title":"Angiotensin receptor blockers and the kidney: possible advantages over ACE inhibition?","authors":"M. Cooper, R. Webb, M. de Gasparo","doi":"10.1111/J.1527-3466.2001.TB00184.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00184.X","url":null,"abstract":"This review deals with similarities and differences between the effects of ACE inhibitors and AT1-receptor blockers in the kidney. Specific receptor blockade has demonstrated that the beneficial effects of AT1 blockers arise from two mechanisms: the reduction of the AT1 receptor mediated response and the increase in plasma levels of Ang II through the AT1-receptor blockade, which leads to increased stimulation of the AT2 receptor (the so-called yin-yang effect). Both ACE inhibition and AT1-receptor blockade provide significant renal protection in the majority of experimental animal models of kidney diseases. AT1 receptor blockade may offer additional clinical benefits over ACE inhibitor treatment, particularly in the kidney, where AT1-receptor blockade does not cause the fall in glomerular filtration rate seen with ACE inhibitor treatment. A number of long-term clinical studies currently running should show the real value of this new class of compounds in the management of hypertension and associated cardiorenal diseases.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85750785","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}
Pub Date : 2006-06-09DOI: 10.1111/J.1527-3466.2001.TB00183.X
A. Saitta, Nunziate Morabito, Nicola Frisina, Domenico Cucinotte, Francesco Corrado, R. D’Anna, D. Altavilla, G. Squadrito, L. Minutoli, Vincenzo Arcoraci, Francesco Cancellieri, F. Squadrito
Raloxifene hydrochloride binds to the estrogen receptor and shows tissue-selective effects; thus, it belongs to a class of drugs recently described as selective estrogen receptor modulators (SERMs). Tissue selectivity of raloxifene may be achieved through several mechanisms: the ligand structure, interaction of the ligand with different receptor subtypes in various tissues, and intracellular events after ligand binding. Raloxifene has estrogen-agonist effects on bone and lipids and estrogen antagonist effects on the breast and uterus. In addition to its well established effects on osteoporosis, recent preclinical and clinical findings suggest that raloxifene also possesses beneficial effects on the cardiovascular system. These findings indicated that raloxifene may have cardioprotective properties without an increased risk of cancer or other side effects. Raloxifene has been shown to reduce total and low-density lipoprotein cholesterol concentrations in plasma, an effect similar to that produced by estrogens. Unlike estrogens, however, raloxifene does not increase high-density lipoprotein cholesterol and triglyceride levels in plasma. Endothelium is thought to play an important role in the genesis of atherosclerosis. Several lines of evidence suggest that an intervention with endothelial function might influence the progression of coronary disease and the incidence of cardiovascular events. Raloxifene increases the nitric oxide/endothelin-1 ratio, and improves endothelium-dependent vasomotion in post-menopausal women to the same extent as estrogens. Furthermore, in two randomized trials on post-menopausal women raloxifene reduced homocysteine levels, another independent risk factor for the development of cardiovascular disease. Although estrogens remain the drugs of choice in the hormonal therapy of most postmenopausal women, raloxifene may represent and alternative in women who are at risk of coronary artery disease.
{"title":"Cardiovascular effects of raloxifene hydrochloride.","authors":"A. Saitta, Nunziate Morabito, Nicola Frisina, Domenico Cucinotte, Francesco Corrado, R. D’Anna, D. Altavilla, G. Squadrito, L. Minutoli, Vincenzo Arcoraci, Francesco Cancellieri, F. Squadrito","doi":"10.1111/J.1527-3466.2001.TB00183.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00183.X","url":null,"abstract":"Raloxifene hydrochloride binds to the estrogen receptor and shows tissue-selective effects; thus, it belongs to a class of drugs recently described as selective estrogen receptor modulators (SERMs). Tissue selectivity of raloxifene may be achieved through several mechanisms: the ligand structure, interaction of the ligand with different receptor subtypes in various tissues, and intracellular events after ligand binding. Raloxifene has estrogen-agonist effects on bone and lipids and estrogen antagonist effects on the breast and uterus. In addition to its well established effects on osteoporosis, recent preclinical and clinical findings suggest that raloxifene also possesses beneficial effects on the cardiovascular system. These findings indicated that raloxifene may have cardioprotective properties without an increased risk of cancer or other side effects. Raloxifene has been shown to reduce total and low-density lipoprotein cholesterol concentrations in plasma, an effect similar to that produced by estrogens. Unlike estrogens, however, raloxifene does not increase high-density lipoprotein cholesterol and triglyceride levels in plasma. Endothelium is thought to play an important role in the genesis of atherosclerosis. Several lines of evidence suggest that an intervention with endothelial function might influence the progression of coronary disease and the incidence of cardiovascular events. Raloxifene increases the nitric oxide/endothelin-1 ratio, and improves endothelium-dependent vasomotion in post-menopausal women to the same extent as estrogens. Furthermore, in two randomized trials on post-menopausal women raloxifene reduced homocysteine levels, another independent risk factor for the development of cardiovascular disease. Although estrogens remain the drugs of choice in the hormonal therapy of most postmenopausal women, raloxifene may represent and alternative in women who are at risk of coronary artery disease.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82019977","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}
Pub Date : 2006-06-09DOI: 10.1111/J.1527-3466.2001.TB00180.X
T. Nagatomo, Y. Hosohata, T. Ohnuki, Takashi Nakamura, K. Hattori, J. Suzuki, M. Ishiguro
: Bopindolol, a non-selective antagonist of beta 1- and beta 2-adrenoceptors (ARs), has been found by pharmacological, molecular biological techniques and molecular modeling to have several unique properties. Bopindolol produces sustained blockade of beta 1- and beta 2-ARs, has intrinsic sympathomimetic as well as membrane stabilizing actions, inhibits renin secretion, and interacts with 5-HT receptors. Also, our recent molecular modeling studies identified possible interaction sites between bopindolol and beta-AR subtypes. The reviewed studies support our findings that bopindolol is non-selective for beta 1- and beta 2-ARs, has low affinity for beta 3-AR subtype and has pharmacological properties that are likely to be beneficial in the treatment of cardiovascular diseases.
{"title":"Bopindolol: Pharmacological Basis and Clinical Implications","authors":"T. Nagatomo, Y. Hosohata, T. Ohnuki, Takashi Nakamura, K. Hattori, J. Suzuki, M. Ishiguro","doi":"10.1111/J.1527-3466.2001.TB00180.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00180.X","url":null,"abstract":": Bopindolol, a non-selective antagonist of beta 1- and beta 2-adrenoceptors (ARs), has been found by pharmacological, molecular biological techniques and molecular modeling to have several unique properties. Bopindolol produces sustained blockade of beta 1- and beta 2-ARs, has intrinsic sympathomimetic as well as membrane stabilizing actions, inhibits renin secretion, and interacts with 5-HT receptors. Also, our recent molecular modeling studies identified possible interaction sites between bopindolol and beta-AR subtypes. The reviewed studies support our findings that bopindolol is non-selective for beta 1- and beta 2-ARs, has low affinity for beta 3-AR subtype and has pharmacological properties that are likely to be beneficial in the treatment of cardiovascular diseases.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75937383","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}
Pub Date : 2006-06-09DOI: 10.1111/J.1527-3466.2001.TB00182.X
L. C. Adding, G. Bannenberg, L. Gustafsson
Gadolinium is a lanthanide that has in recent years become more commonly present in our society. Organic chelates of gadolinium are increasingly used as contrast agents for the imaging of body fluids. Although adverse reactions to these agents are uncommon, it is known that gadolinium salts can bring about a wide variety of changes in physiology. Gadolinium chloride is widely used experimentally as an inhibitor of stretch-activated ion channels and physiological responses of tissues to mechanical stimulation. It is also employed as a selective inhibitor of macrophages in vivo. In this review, the known biochemical actions of gadolinium are brought together with its in vivo pharmacology and toxicology.
{"title":"Basic experimental studies and clinical aspects of gadolinium salts and chelates.","authors":"L. C. Adding, G. Bannenberg, L. Gustafsson","doi":"10.1111/J.1527-3466.2001.TB00182.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00182.X","url":null,"abstract":"Gadolinium is a lanthanide that has in recent years become more commonly present in our society. Organic chelates of gadolinium are increasingly used as contrast agents for the imaging of body fluids. Although adverse reactions to these agents are uncommon, it is known that gadolinium salts can bring about a wide variety of changes in physiology. Gadolinium chloride is widely used experimentally as an inhibitor of stretch-activated ion channels and physiological responses of tissues to mechanical stimulation. It is also employed as a selective inhibitor of macrophages in vivo. In this review, the known biochemical actions of gadolinium are brought together with its in vivo pharmacology and toxicology.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86567094","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}
Pub Date : 2006-06-09DOI: 10.1111/J.1527-3466.2001.TB00179.X
Toyoki Mori, H. Takase, K. Toide, T. Hirano, Toshimi Kambe, N. Nakayama, Arnold Schwartz
Pranidipine, a long acting 1,4-dihydropyridine calcium channel blocker, prolongs nitric oxide (NO)-mediated relaxation of rat aorta; it prolongs acetylcholine-induced relaxation in presence of endothelium as well as nitroglycerin-induced relaxation in absence of endothelium. In rat aorta the effect of pranidipine on NO-mediated relaxation is cyclic guanosine monophosphate (cGMP)-independent, but in guinea pig carotid artery the same effect of pranidipine is cGMP-dependent. It has been reported that in co-cultured human endothelial and smooth muscle cells pranidipine, at a higher concentration (10(-6) M), enhances vasorelaxant effect of NO by blocking NO decomposition. The enhancement of NO action by pranidipine differs from the direct NO-releasing action of other 1,4-dihydropyridines. It is expected that enhancement of NO-induced vasodilatation will lead to a venodilator action in vivo and less peripheral edema. The target organ protective effects of pranidipine are also reviewed in this article.
{"title":"Pranidipine, a 1,4-dihydropyridine calcium channel blocker that enhances nitric oxide-induced vascular relaxation.","authors":"Toyoki Mori, H. Takase, K. Toide, T. Hirano, Toshimi Kambe, N. Nakayama, Arnold Schwartz","doi":"10.1111/J.1527-3466.2001.TB00179.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00179.X","url":null,"abstract":"Pranidipine, a long acting 1,4-dihydropyridine calcium channel blocker, prolongs nitric oxide (NO)-mediated relaxation of rat aorta; it prolongs acetylcholine-induced relaxation in presence of endothelium as well as nitroglycerin-induced relaxation in absence of endothelium. In rat aorta the effect of pranidipine on NO-mediated relaxation is cyclic guanosine monophosphate (cGMP)-independent, but in guinea pig carotid artery the same effect of pranidipine is cGMP-dependent. It has been reported that in co-cultured human endothelial and smooth muscle cells pranidipine, at a higher concentration (10(-6) M), enhances vasorelaxant effect of NO by blocking NO decomposition. The enhancement of NO action by pranidipine differs from the direct NO-releasing action of other 1,4-dihydropyridines. It is expected that enhancement of NO-induced vasodilatation will lead to a venodilator action in vivo and less peripheral edema. The target organ protective effects of pranidipine are also reviewed in this article.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91506680","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}
Pub Date : 2006-06-09DOI: 10.1111/J.1527-3466.2001.TB00181.X
K. Baba, Y. Aga, T. Nakanishi, T. Motoyama, H. Ueno
UR-3216, a prodrug, is a novel, selective, and orally active platelet surface glycoprotein (GPIIb/IIIa) receptor antagonist. The most important property of UR-3216 is the very tight binding of its active metabolite to platelets (Ki for resting platelets is < 1 nM). UR-2992, the active form of UR-3216, binds to platelets for a long period of time, while the unbound drug is rapidly cleared. Therefore, after an initial loading dose of 0.1 mg/kg, only once daily repeated low maintenance doses of UR-3216 (< 0.05 mg/kg p.o.) are required. This regimen maintains a high level of inhibition of platelet aggregation and, due to a small peak-to-trough ratio, severe bleeding is avoided. The therapy with UR-3216 is easy to manage, because it has low peak-to-trough ratio and high efficacy (> 80% inhibition of platelet aggregation). In addition, UR-3216 does not produce excessive bleeding or thrombocytopenia and does not interact with abciximab. UR-3216 is excreted mostly in bile, so that it will not accumulate in patients with chronic renal dysfunction. UR-2316 has the following abciximab-like features: (a) its half-lives for residence on platelets, inhibition of platelets aggregation and bleeding time prolongation are 60 to 80 h, 24, and 2 h, respectively; (b) its receptor binding occupancy is similar to that of abciximab (Mab1 is inhibited and Mab2 is unaltered). In conclusion, UR-3216 is a promising, orally active GPIIb/IIIa antagonist for the treatment of cardiovascular diseases.
{"title":"UR-3216: a manageable oral GPIIb/IIIa antagonist.","authors":"K. Baba, Y. Aga, T. Nakanishi, T. Motoyama, H. Ueno","doi":"10.1111/J.1527-3466.2001.TB00181.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00181.X","url":null,"abstract":"UR-3216, a prodrug, is a novel, selective, and orally active platelet surface glycoprotein (GPIIb/IIIa) receptor antagonist. The most important property of UR-3216 is the very tight binding of its active metabolite to platelets (Ki for resting platelets is < 1 nM). UR-2992, the active form of UR-3216, binds to platelets for a long period of time, while the unbound drug is rapidly cleared. Therefore, after an initial loading dose of 0.1 mg/kg, only once daily repeated low maintenance doses of UR-3216 (< 0.05 mg/kg p.o.) are required. This regimen maintains a high level of inhibition of platelet aggregation and, due to a small peak-to-trough ratio, severe bleeding is avoided. The therapy with UR-3216 is easy to manage, because it has low peak-to-trough ratio and high efficacy (> 80% inhibition of platelet aggregation). In addition, UR-3216 does not produce excessive bleeding or thrombocytopenia and does not interact with abciximab. UR-3216 is excreted mostly in bile, so that it will not accumulate in patients with chronic renal dysfunction. UR-2316 has the following abciximab-like features: (a) its half-lives for residence on platelets, inhibition of platelets aggregation and bleeding time prolongation are 60 to 80 h, 24, and 2 h, respectively; (b) its receptor binding occupancy is similar to that of abciximab (Mab1 is inhibited and Mab2 is unaltered). In conclusion, UR-3216 is a promising, orally active GPIIb/IIIa antagonist for the treatment of cardiovascular diseases.","PeriodicalId":9490,"journal":{"name":"Cardiovascular drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88623938","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3466.2001.TB00068.X
C. Lau, X. Yao, Z. Chen, W. Ko, Yu Huang
Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8-oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some cardiovascular effects of berberine and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.
{"title":"Cardiovascular actions of berberine.","authors":"C. Lau, X. Yao, Z. Chen, W. Ko, Yu Huang","doi":"10.1111/J.1527-3466.2001.TB00068.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00068.X","url":null,"abstract":"Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8-oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some cardiovascular effects of berberine and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.","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":"84284463","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3466.2001.TB00075.X
M. Endoh, H. Sugawara, M. Mineshima
Cardiotonic agents that facilitate cardiac pump function by direct improvement of contractile dysfunction are indispensable for the treatment of hemodynamic disorders in acute myocardial failure and the aggravating phase of congestive heart failure. Cardiotonic agents currently available for the treatment of hemodynamic crisis in congestive heart failure are catecholamines, selective phosphodiesterase (PDE) III inhibitors and digitalis, all of which are Ca2+ mobilizers. Considering the number of serious adverse effects of these clinically available cardiotonic agents, development of agents that act via a novel mechanism of action may contribute to the progress of pharmacotherapy of congestive heart failure. Ca2+ sensitizers that act by increasing in myofilament Ca2+ sensitivity may be able to overcome the disadvantage of Ca2+ mobilizers. Ca2+ sensitizers do not increase activation energy, do not produce Ca2+ overload and may be effective even under pathophysiological states such as acidosis, myocardial stunning and heart failure. SCH00013 ((4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5,6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one)) is a novel Ca2+ sensitizer that elicits a moderate positive inotropic effect without significant alteration of Ca2+ transients. SCH00013 does not have a positive chronotropic effect and has a weak PDE III inhibitory action and class III antiarrhythmic action. SCH00013 prolonged the survival in a animal heart failure model with genetic cardiomyopathy. The oral bioavailability of SCH00013 is high and equivalent to that via intravenous administration. The unique pharmacological profiles of SCH00013 imply that this agent may be potentially beneficial for pharmacotherapy of contractile dysfunction in congestive heart failure.
{"title":"Pharmacology of SCH00013: a novel Ca2+ sensitizer.","authors":"M. Endoh, H. Sugawara, M. Mineshima","doi":"10.1111/J.1527-3466.2001.TB00075.X","DOIUrl":"https://doi.org/10.1111/J.1527-3466.2001.TB00075.X","url":null,"abstract":"Cardiotonic agents that facilitate cardiac pump function by direct improvement of contractile dysfunction are indispensable for the treatment of hemodynamic disorders in acute myocardial failure and the aggravating phase of congestive heart failure. Cardiotonic agents currently available for the treatment of hemodynamic crisis in congestive heart failure are catecholamines, selective phosphodiesterase (PDE) III inhibitors and digitalis, all of which are Ca2+ mobilizers. Considering the number of serious adverse effects of these clinically available cardiotonic agents, development of agents that act via a novel mechanism of action may contribute to the progress of pharmacotherapy of congestive heart failure. Ca2+ sensitizers that act by increasing in myofilament Ca2+ sensitivity may be able to overcome the disadvantage of Ca2+ mobilizers. Ca2+ sensitizers do not increase activation energy, do not produce Ca2+ overload and may be effective even under pathophysiological states such as acidosis, myocardial stunning and heart failure. SCH00013 ((4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5,6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one)) is a novel Ca2+ sensitizer that elicits a moderate positive inotropic effect without significant alteration of Ca2+ transients. SCH00013 does not have a positive chronotropic effect and has a weak PDE III inhibitory action and class III antiarrhythmic action. SCH00013 prolonged the survival in a animal heart failure model with genetic cardiomyopathy. The oral bioavailability of SCH00013 is high and equivalent to that via intravenous administration. The unique pharmacological profiles of SCH00013 imply that this agent may be potentially beneficial for pharmacotherapy of contractile dysfunction in congestive heart failure.","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":"89626178","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}
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