Nesiritide

Chemical Identity

Property	Value
Chemical Formula	C143H244N50O42S4
Molecular Weight	3464 Da
CAS Number	124584-08-3
Peptide Class	Recombinant Natriuretic Peptide (32 aa)
Sequence	Human BNP(1-32)
Disulfide Bonds	1

Structure

Nesiritide (Natrecor) is recombinant human B-type natriuretic peptide (BNP), identical to the endogenous 32-amino acid hormone secreted by ventricular cardiomyocytes in response to volume overload and increased wall stress. It contains a 17-amino acid ring structure formed by an intramolecular disulfide bond.

Mechanism of Action

Nesiritide binds natriuretic peptide receptor A (NPR-A) on vascular smooth muscle and renal tubular cells, activating guanylyl cyclase and increasing cGMP. This produces balanced vasodilation (arterial and venous), natriuresis, diuresis, and suppression of the renin-angiotensin-aldosterone system and sympathetic nervous system.

Clinical Applications

• Acute decompensated heart failure: Dyspnea relief (Natrecor)
• Pulmonary hypertension: Reduction of pulmonary capillary wedge pressure
• Diuretic-resistant edema: Adjunct to loop diuretics
• Cardiorenal syndrome: Renal protective effects

Pharmacokinetics

• Half-life: 18 minutes
• Onset: 2-15 minutes
• Duration: 60 minutes after infusion cessation
• Metabolism: Endopeptidase cleavage and NPR-C receptor clearance
• Route: IV bolus (2 mcg/kg) + infusion (0.01 mcg/kg/min)

Safety and Side Effects

Hypotension (dose-limiting), headache, nausea, dizziness, and back pain. Controversial renal effects (ROSE-AHF trial). Use with caution in patients with systolic BP <100 mmHg.

References

• Colucci, W.S., et al. (2000). VMAC trial: nesiritide for heart failure. New England Journal of Medicine, 343, 246-253.
• O’Connor, C.M., et al. (2011). ASCEND-HF trial: nesiritide for acute heart failure. New England Journal of Medicine, 365, 32-43.