The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Barbara Albrechtkupper - One of the best experts on this subject based on the ideXlab platform.
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neladenoson bialanate hydrochloride a prodrug of a partial adenosine a1 receptor agonist for the chronic treatment of heart diseases
ChemMedChem, 2017Co-Authors: Daniel Meibom, Nicole Diedrichs, Barbara Albrechtkupper, Walter Hubsch, Raimund Kast, Thomas Dr Kramer, Ursula Krenz, Hansgeorg Lerchen, Joachim Mittendorf, Peter NellAbstract:Adenosine is known to be released under a variety of physiological and pathophysiological conditions to facilitate the protection and regeneration of injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1Rs) has been shown to inhibit myocardial pathologies associated with ischemia and reperfusion injury, suggesting several options for new cardiovascular therapies. When full A1R agonists are used, the desired protective and regenerative cardiovascular effects are usually overshadowed by unintended pharmacological effects such as induction of bradycardia, atrioventricular (AV) blocks, and sedation. These unwanted effects can be overcome by using partial A1R agonists. Starting from previously reported cApadenoson we evaluated options to tailor A1R agonists to a specific partiality range, thereby optimizing the therapeutic window. This led to the identification of the potent and selective agonist neladenoson, which shows the desired partial response on the A1R, resulting in cardioprotection without sedative effects or cardiac AV blocks. To circumvent solubility and formulation issues for neladenoson, a prodrug approach was pursued. The dipeptide ester neladenoson bialanate hydrochloride showed significantly improved solubility and exposure after oral administration. Neladenoson bialanate hydrochloride is currently being evaluated in clinical trials for the treatment of heart failure.
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chronic therapy with a partial adenosine a1 receptor agonist improves left ventricular function and remodeling in dogs with advanced heart failure
Circulation-heart Failure, 2013Co-Authors: Hani N Sabbah, Ramesh C Gupta, Smita Kohli, Mengjun Wang, Sharad Rastogi, Kefei Zhang, Katja Zimmermann, Nicole Diedrichs, Barbara AlbrechtkupperAbstract:Background—Adenosine elicits cardioprotection through A1-receptor activation. Therapy with adenosine A1-receptor agonists, however, is limited by undesirable actions of full agonism, such as bradycardia. This study examined the effects of cApadenoson (CAP), a partial adenosine A1-receptor agonist, on left ventricular (LV) function and remodeling in dogs with heart failure. Methods and Results—Twelve dogs with microembolization-induced heart failure were randomized to 12 weeks oral therapy with CAP (7.5 mg BID; n=6) or to no therapy (control; n=6). LV end-diastolic and end-systolic volumes, ejection fraction, plasma norepinephrine, and n-terminal pro–brain natriuretic peptide were measured before (pre) and 1 and 12 weeks after therapy (post). LV tissue obtained at post was used to assess volume fraction of interstitial fibrosis, sarcoplasmic reticulum calcium ATPase-2a activity, expression of mitochondria uncoupling proteins (UCP) and glucose transporters (GLUT). In controls, end-diastolic and end-systolic...
Nicole Diedrichs - One of the best experts on this subject based on the ideXlab platform.
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neladenoson bialanate hydrochloride a prodrug of a partial adenosine a1 receptor agonist for the chronic treatment of heart diseases
ChemMedChem, 2017Co-Authors: Daniel Meibom, Nicole Diedrichs, Barbara Albrechtkupper, Walter Hubsch, Raimund Kast, Thomas Dr Kramer, Ursula Krenz, Hansgeorg Lerchen, Joachim Mittendorf, Peter NellAbstract:Adenosine is known to be released under a variety of physiological and pathophysiological conditions to facilitate the protection and regeneration of injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1Rs) has been shown to inhibit myocardial pathologies associated with ischemia and reperfusion injury, suggesting several options for new cardiovascular therapies. When full A1R agonists are used, the desired protective and regenerative cardiovascular effects are usually overshadowed by unintended pharmacological effects such as induction of bradycardia, atrioventricular (AV) blocks, and sedation. These unwanted effects can be overcome by using partial A1R agonists. Starting from previously reported cApadenoson we evaluated options to tailor A1R agonists to a specific partiality range, thereby optimizing the therapeutic window. This led to the identification of the potent and selective agonist neladenoson, which shows the desired partial response on the A1R, resulting in cardioprotection without sedative effects or cardiac AV blocks. To circumvent solubility and formulation issues for neladenoson, a prodrug approach was pursued. The dipeptide ester neladenoson bialanate hydrochloride showed significantly improved solubility and exposure after oral administration. Neladenoson bialanate hydrochloride is currently being evaluated in clinical trials for the treatment of heart failure.
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chronic therapy with a partial adenosine a1 receptor agonist improves left ventricular function and remodeling in dogs with advanced heart failure
Circulation-heart Failure, 2013Co-Authors: Hani N Sabbah, Ramesh C Gupta, Smita Kohli, Mengjun Wang, Sharad Rastogi, Kefei Zhang, Katja Zimmermann, Nicole Diedrichs, Barbara AlbrechtkupperAbstract:Background—Adenosine elicits cardioprotection through A1-receptor activation. Therapy with adenosine A1-receptor agonists, however, is limited by undesirable actions of full agonism, such as bradycardia. This study examined the effects of cApadenoson (CAP), a partial adenosine A1-receptor agonist, on left ventricular (LV) function and remodeling in dogs with heart failure. Methods and Results—Twelve dogs with microembolization-induced heart failure were randomized to 12 weeks oral therapy with CAP (7.5 mg BID; n=6) or to no therapy (control; n=6). LV end-diastolic and end-systolic volumes, ejection fraction, plasma norepinephrine, and n-terminal pro–brain natriuretic peptide were measured before (pre) and 1 and 12 weeks after therapy (post). LV tissue obtained at post was used to assess volume fraction of interstitial fibrosis, sarcoplasmic reticulum calcium ATPase-2a activity, expression of mitochondria uncoupling proteins (UCP) and glucose transporters (GLUT). In controls, end-diastolic and end-systolic...
Hani N Sabbah - One of the best experts on this subject based on the ideXlab platform.
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chronic therapy with a partial adenosine a1 receptor agonist improves left ventricular function and remodeling in dogs with advanced heart failure
Circulation-heart Failure, 2013Co-Authors: Hani N Sabbah, Ramesh C Gupta, Smita Kohli, Mengjun Wang, Sharad Rastogi, Kefei Zhang, Katja Zimmermann, Nicole Diedrichs, Barbara AlbrechtkupperAbstract:Background—Adenosine elicits cardioprotection through A1-receptor activation. Therapy with adenosine A1-receptor agonists, however, is limited by undesirable actions of full agonism, such as bradycardia. This study examined the effects of cApadenoson (CAP), a partial adenosine A1-receptor agonist, on left ventricular (LV) function and remodeling in dogs with heart failure. Methods and Results—Twelve dogs with microembolization-induced heart failure were randomized to 12 weeks oral therapy with CAP (7.5 mg BID; n=6) or to no therapy (control; n=6). LV end-diastolic and end-systolic volumes, ejection fraction, plasma norepinephrine, and n-terminal pro–brain natriuretic peptide were measured before (pre) and 1 and 12 weeks after therapy (post). LV tissue obtained at post was used to assess volume fraction of interstitial fibrosis, sarcoplasmic reticulum calcium ATPase-2a activity, expression of mitochondria uncoupling proteins (UCP) and glucose transporters (GLUT). In controls, end-diastolic and end-systolic...
Peter Nell - One of the best experts on this subject based on the ideXlab platform.
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neladenoson bialanate hydrochloride a prodrug of a partial adenosine a1 receptor agonist for the chronic treatment of heart diseases
ChemMedChem, 2017Co-Authors: Daniel Meibom, Nicole Diedrichs, Barbara Albrechtkupper, Walter Hubsch, Raimund Kast, Thomas Dr Kramer, Ursula Krenz, Hansgeorg Lerchen, Joachim Mittendorf, Peter NellAbstract:Adenosine is known to be released under a variety of physiological and pathophysiological conditions to facilitate the protection and regeneration of injured ischemic tissues. The activation of myocardial adenosine A1 receptors (A1Rs) has been shown to inhibit myocardial pathologies associated with ischemia and reperfusion injury, suggesting several options for new cardiovascular therapies. When full A1R agonists are used, the desired protective and regenerative cardiovascular effects are usually overshadowed by unintended pharmacological effects such as induction of bradycardia, atrioventricular (AV) blocks, and sedation. These unwanted effects can be overcome by using partial A1R agonists. Starting from previously reported cApadenoson we evaluated options to tailor A1R agonists to a specific partiality range, thereby optimizing the therapeutic window. This led to the identification of the potent and selective agonist neladenoson, which shows the desired partial response on the A1R, resulting in cardioprotection without sedative effects or cardiac AV blocks. To circumvent solubility and formulation issues for neladenoson, a prodrug approach was pursued. The dipeptide ester neladenoson bialanate hydrochloride showed significantly improved solubility and exposure after oral administration. Neladenoson bialanate hydrochloride is currently being evaluated in clinical trials for the treatment of heart failure.
Mengjun Wang - One of the best experts on this subject based on the ideXlab platform.
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chronic therapy with a partial adenosine a1 receptor agonist improves left ventricular function and remodeling in dogs with advanced heart failure
Circulation-heart Failure, 2013Co-Authors: Hani N Sabbah, Ramesh C Gupta, Smita Kohli, Mengjun Wang, Sharad Rastogi, Kefei Zhang, Katja Zimmermann, Nicole Diedrichs, Barbara AlbrechtkupperAbstract:Background—Adenosine elicits cardioprotection through A1-receptor activation. Therapy with adenosine A1-receptor agonists, however, is limited by undesirable actions of full agonism, such as bradycardia. This study examined the effects of cApadenoson (CAP), a partial adenosine A1-receptor agonist, on left ventricular (LV) function and remodeling in dogs with heart failure. Methods and Results—Twelve dogs with microembolization-induced heart failure were randomized to 12 weeks oral therapy with CAP (7.5 mg BID; n=6) or to no therapy (control; n=6). LV end-diastolic and end-systolic volumes, ejection fraction, plasma norepinephrine, and n-terminal pro–brain natriuretic peptide were measured before (pre) and 1 and 12 weeks after therapy (post). LV tissue obtained at post was used to assess volume fraction of interstitial fibrosis, sarcoplasmic reticulum calcium ATPase-2a activity, expression of mitochondria uncoupling proteins (UCP) and glucose transporters (GLUT). In controls, end-diastolic and end-systolic...