Abstract
CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino-acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B, but without inducing excessive hypotension. Here we report the first-in-human studies for CD-NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic guanosine monophosphate-activating, natriuretic, and aldosterone-suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first-in-class new cardiovascular therapeutic in human heart failure, which are now underway worldwide.
Publication types
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Clinical Trial, Phase I
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Clinical Trial, Phase II
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Randomized Controlled Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Blood Pressure / drug effects
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Cardiovascular Agents / administration & dosage
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Cardiovascular Agents / adverse effects
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Cardiovascular Agents / pharmacology*
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Cyclic GMP / blood
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Cyclic GMP / urine
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Drug Design
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Elapid Venoms / administration & dosage
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Elapid Venoms / adverse effects
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Elapid Venoms / pharmacology*
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Female
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Glomerular Filtration Rate / drug effects
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Humans
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Male
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Middle Aged
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Natriuretic Peptide, C-Type / administration & dosage
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Natriuretic Peptide, C-Type / adverse effects
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Natriuretic Peptide, C-Type / pharmacology*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / adverse effects
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Recombinant Fusion Proteins / pharmacology
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Sodium / urine
Substances
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CD-NP natriuretic peptide
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Cardiovascular Agents
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Elapid Venoms
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Recombinant Fusion Proteins
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Natriuretic Peptide, C-Type
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Sodium
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Cyclic GMP