124584-08-3

Nesiritide was introduced in the US as a new intravenous treatment for patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. Nesiritide is the first human recombinant form of the potent vasodilatory B-type natriuretic peptide (also known as brain natriuretic peptide), a naturally occurring 32 amino acid peptide with a disulfide-bonded 17 amino acid ring structure. Nesiritide binds to the Atype natriuretic peptide receptor on the surface of endothelial and smooth muscle cells stimulating production of the second messenger cGMP which mediates predominantly vascular smooth muscle cell relaxation. It also facilitates the elimination of sodium and water by the kidney and decreases the secretion of certain hormones, such as adrenalin, angiotensin II, aldosterone and endothelin, which provoke long-term detrimental effects including blood vessel constriction and blood pressure elevation. In clinical trials with heart failure patients, nesidtide dose-dependently reduced pulmonary capillary wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index without affecting heart rate. The major adverse effect observed was dose-dependent hypotension. In a phase III comparative trial, nesiritide was found to be superior to iv. nitroglycerine in its haemodynamic effects as well as easier to administer and better tolerated. Nesiritide is cleared by proteolytic cleavage by the enzyme neutral endopeptidase NEP24.11 and by binding to the C-type natriuretic peptide receptor followed by endocytosis and intracellular lysosomal hydrolysis. Since it has a short half-life (18 min), nesiritide is administered as a 21μg/kg bolus infusion followed by a continuous maintenance infusion at 0.011μg/kg/min usually over 24-48 hours.

Scios (US)

Treatment of congestive heart failure (renin-angiotensin system antagonist).

Natrecor (Biochemie, Austria).

Control peptide for Brain Natriuretic Peptide Antibody (BML-BA1117). Blocks antibody reactivity at 100 nmol/ml diluted antiserum.

Brain natriuretic peptide (type B natriuretic peptide) was originally isolated from brain, but is mainly produced in myoendocrine cells of the heart ventricles from which it is released into the circulation. It is involved in blood pressure control and cardiovascular homeostasis.

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