Nesiritide

Chemical Identity

Property	Value
Chemical Formula	C143H244N50O42S4
Molecular Weight	3464.04 g/mol
CAS Number	124584-08-3
IUPAC Name	Recombinant human BNP(1-32)
Peptide Class	Natriuretic Peptide
Sequence Homology	Identical to endogenous human BNP(1-32)

Structure

Nesiritide is a recombinant form of human B-type natriuretic peptide (BNP), identical in amino acid sequence to the endogenous 32-amino acid hormone produced by ventricular cardiomyocytes. BNP contains a 17-amino acid ring structure formed by an intramolecular disulfide bond between two cysteine residues, which is essential for receptor binding and biological activity.

Mechanism of Action

Nesiritide binds to natriuretic peptide receptor A (NPR-A) on vascular smooth muscle and renal tubular cells, activating guanylyl cyclase and increasing intracellular cGMP. This produces:

• Vasodilation: Balanced arterial and venous dilation, reducing preload and afterload
• Natriuresis: Increased sodium and water excretion via the kidney
• RAAS suppression: Inhibition of renin and aldosterone secretion
• Sympatholytic effects: Reduced sympathetic nervous system activation

Unlike nitroprusside, nesiritide does not cause reflex tachycardia.

Clinical Applications

Nesiritide (Natrecor) is approved for:

• Acute decompensated heart failure (ADHF): IV therapy for dyspnea at rest or with minimal exertion
• Symptom relief: Rapid reduction of pulmonary capillary wedge pressure and dyspnea

Administered as a 2 mcg/kg IV bolus followed by 0.01 mcg/kg/min continuous infusion. Effects are rapid in onset (within 15 minutes).

Pharmacokinetics

• Half-life: 18 minutes (initial distribution); 132 minutes (terminal)
• Tmax: Immediate (IV bolus)
• Metabolism: Proteolytic degradation by NEP and clearance receptors
• Elimination: Renal and receptor-mediated clearance
• Dose adjustment: Not required for renal impairment

Safety and Side Effects

Hypotension (dose-limiting, 11-35%), headache (8%), nausea (4%), and dizziness (3%). Symptomatic hypotension may persist for hours after discontinuation. The ASCEND-HF trial showed no increase in mortality or renal injury compared to placebo, but also no reduction in 30-day mortality or heart failure rehospitalization. Use caution in patients with systolic BP <100 mmHg.

References

• Colucci, W.S., et al. (2000). Intravenous nesiritide, a natriuretic peptide, in the treatment of symptomatic congestive heart failure. New England Journal of Medicine, 343, 246-253.
• O’Connor, C.M., et al. (2011). Effect of nesiritide in patients with acute decompensated heart failure. New England Journal of Medicine, 365, 32-43.