Pharmacodynamic Hybrids Coupling Established Cardiovascular Mechanisms of Action with Additional Nitric Oxide Releasing Properties

Alma      Martelli; Maria   Cristina   Breschi; Vincenzo      Calderone

Abstract

The pharmacotherapy of complex pathological states at the cardiovascular level often requires different and complementary pharmacodynamic properties. This is frequently achieved through the administration of “cocktails”, composed by several drugs possessing different mechanisms of action. In the last years, a revision of the “one-compound-onetarget” paradigm led to a wide development of new classes of molecules, possessing more pharmacological targets. Among them, this innovative strategy produced interesting hybrid drugs, with a dual mechanism of action: a) a fundamental and well-established pharmacodynamic profile and b) the release of nitric oxide (NO), playing a pivotal role in the modulation of the function of cardiovascular system, where it induces vasorelaxing and antiplatelet responses. These new pharmacodynamic hybrids present the advantage of adding to a main mechanism of action (for example, cyclooxygenase inhibition, beta-antagonism or ACE-inhibition) also a slow release of NO, useful either to reduce the adverse side effects and/or to improve the effectiveness of the drug. This review presents the chemical features of many examples of NO-releasing hybrids of cardiovascular drugs and explains the pharmacological improvements conferred by the addition of such NO-donor properties.

Keywords: Nitric oxide, cardiovascular drugs, pharmacodynamic hybrids, multi-target drugs

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Current Pharmaceutical Design

Title: Pharmacodynamic Hybrids Coupling Established Cardiovascular Mechanisms of Action with Additional Nitric Oxide Releasing Properties

Volume: 15 Issue: 6

Author(s): Alma Martelli, Maria Cristina Breschi and Vincenzo Calderone

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Keywords: Nitric oxide, cardiovascular drugs, pharmacodynamic hybrids, multi-target drugs

Abstract: The pharmacotherapy of complex pathological states at the cardiovascular level often requires different and complementary pharmacodynamic properties. This is frequently achieved through the administration of “cocktails”, composed by several drugs possessing different mechanisms of action. In the last years, a revision of the “one-compound-onetarget” paradigm led to a wide development of new classes of molecules, possessing more pharmacological targets. Among them, this innovative strategy produced interesting hybrid drugs, with a dual mechanism of action: a) a fundamental and well-established pharmacodynamic profile and b) the release of nitric oxide (NO), playing a pivotal role in the modulation of the function of cardiovascular system, where it induces vasorelaxing and antiplatelet responses. These new pharmacodynamic hybrids present the advantage of adding to a main mechanism of action (for example, cyclooxygenase inhibition, beta-antagonism or ACE-inhibition) also a slow release of NO, useful either to reduce the adverse side effects and/or to improve the effectiveness of the drug. This review presents the chemical features of many examples of NO-releasing hybrids of cardiovascular drugs and explains the pharmacological improvements conferred by the addition of such NO-donor properties.

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Martelli Alma, Breschi Cristina Maria and Calderone Vincenzo, Pharmacodynamic Hybrids Coupling Established Cardiovascular Mechanisms of Action with Additional Nitric Oxide Releasing Properties, Current Pharmaceutical Design 2009; 15 (6) . https://dx.doi.org/10.2174/138161209787315611

DOI https://dx.doi.org/10.2174/138161209787315611	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286

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