Nesiritide is a medication used to treat acutely decompensated congestive heart failure with dyspnea at rest or with minimal exertion (such as talk, eating or bathing). Nesiritide is the recombinant form of the 32 amino acid human B-type natriuretic peptide, which is normally produced by the ventricular myocardium.

Protein structure

Protein chemical formula

Not Available

Protein average weight

3464.0 Da

Sequences

>DB04899: Natriuretic peptides B
SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH

Download FASTA Format

Synonyms

BNP
Brain natriuretic peptide 32
Natriuretic peptides B
Nesiritide recombinant

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Natrecor	Injection, powder, lyophilized, for solution	1.5 mg/5mL	Intravenous	Scios, Inc.	2001-08-01	Not applicable
Natrecor	Powder, for solution	1.5 mg	Intravenous	Janssen Pharmaceuticals	2008-02-05	2012-08-01

Categories

UNII

P7WI8UL647

CAS number

124584-08-3

Pharmacology

Indication

For the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity.

Associated Conditions

Acute Decompensated Heart Failure (ADHF)

Pharmacodynamics

Nesiritide works to facilitate cardiovascular fluid homeostasis through counterregulation of the renin-angiotensin-aldoesterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation. In simpler terms, it promotes vasodilation, natriuresis, and diuresis.

Mechanism of action

Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of guanosine 3'5'-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide has been shown to relax isolated human arterial and venous tissue preparations that were precontracted with either endothelin-1 or the alpha-adrenergic agonist, phenylephrine. In human studies, nesiritide produced dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure. In animals, nesiritide had no effects on cardiac contractility or on measures of cardiac electrophysiology such as atrial and ventricular effective refractory times or atrioventricular node conduction. Naturally occurring atrial natriuretic peptide (ANP), a related peptide, increases vascular permeability in animals and humans and may reduce intravascular volume. The effect of nesiritide on vascular permeability has not been studied.

Target	Actions	Organism
UAtrial natriuretic peptide receptor 1	binder	Humans
UAtrial natriuretic peptide receptor 2	Not Available	Humans
UAtrial natriuretic peptide receptor 3	Not Available	Humans

Absorption

Administration of nesiritide exhibits biphasic disposition from the plasma.

Volume of distribution

0.19 L/kg

Protein binding

Not Available

Metabolism

Nesiritide undergoes proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface.

Route of elimination

Human BNP is cleared from the circulation via the following three independent mechanisms, in order of decreasing importance: 1) binding to cell surface clearance receptors with subsequent cellular internalization and lysosomal proteolysis; 2) proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface; and 3) renal filtration.

Half life

Approximately 18 minutes

Clearance

9.2 mL/min/k [patients with congestive heart failure receiving IV infusion]

Toxicity

No data are available with respect to overdosage in humans. The expected reaction would be excessive hypotension, which should be treated with drug discontinuation or reduction and appropriate measures.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
Acebutolol	The risk or severity of adverse effects can be increased when Acebutolol is combined with Nesiritide.
Aldesleukin	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Nesiritide.
Aliskiren	The risk or severity of adverse effects can be increased when Nesiritide is combined with Aliskiren.
Amifostine	The risk or severity of adverse effects can be increased when Amifostine is combined with Nesiritide.
Amiloride	The risk or severity of adverse effects can be increased when Amiloride is combined with Nesiritide.
Amiodarone	The risk or severity of adverse effects can be increased when Amiodarone is combined with Nesiritide.
Amlodipine	The risk or severity of adverse effects can be increased when Amlodipine is combined with Nesiritide.
Amobarbital	Amobarbital may increase the hypotensive activities of Nesiritide.
Amphotericin B	The risk or severity of adverse effects can be increased when Amphotericin B is combined with Nesiritide.
Amyl Nitrite	The risk or severity of adverse effects can be increased when Amyl Nitrite is combined with Nesiritide.

Food Interactions

Not Available

References

General References

Jefferies JL, Price JF, Denfield SW, Chang AC, Dreyer WJ, McMahon CJ, Grenier MA, Clunie SK, Thomas A, Moffett BS, Wann TS, Smith EO, Towbin JA: Safety and efficacy of nesiritide in pediatric heart failure. J Card Fail. 2007 Sep;13(7):541-8. [PubMed:17826644]
Maisel AS: Nesiritide: a new therapy for the treatment of heart failure. Cardiovasc Toxicol. 2003;3(1):37-42. [PubMed:12668889]
Vichiendilokkul A, Tran A, Racine E: Nesiritide: a novel approach for acute heart failure. Ann Pharmacother. 2003 Feb;37(2):247-58. [PubMed:12549957]
Cheng JW: Nesiritide: review of clinical pharmacology and role in heart failure management. Heart Dis. 2002 May-Jun;4(3):199-203. [PubMed:12028606]
Bettencourt P: Brain natriuretic peptide (nesiritide) in the treatment of heart failure. Cardiovasc Drug Rev. 2002 Winter;20(1):27-36. [PubMed:12070532]

External Links

UniProt: P16860
PubChem Substance: 46508506
ChEMBL: CHEMBL1201668
Therapeutic Targets Database: DAP001320
PharmGKB: PA164781045
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Nesiritide

ATC Codes

C01DX19 — Nesiritide

FDA label

Download (205 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Withdrawn	Other	BMI >30 kg/m2 / Hyperinsulinemia	1
1	Completed	Basic Science	BMI >30 kg/m2 / Cardiovascular Disease (CVD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension)	1
1	Terminated	Basic Science	Congestive Heart Failure (CHF) / Renal Dysfunction	1
1, 2	Completed	Basic Science	Asymptomatic Systolic Dysfunction / Heart Failure, Unspecified	1
1, 2	Completed	Basic Science	Congestive Heart Failure (CHF)	1
1, 2	Completed	Basic Science	Left Ventricular Diastolic Dysfunction	1
1, 2	Completed	Prevention	Congestive Heart Failure (CHF)	1
1, 2	Completed	Treatment	Acute Renal Failure (ARF)	1
1, 2	Completed	Treatment	Congestive Heart Failure (CHF) / Prophylaxis of cardiomyopathy	1
1, 2	Completed	Treatment	Diastolic Heart Failure	1
1, 2	Enrolling by Invitation	Treatment	Heart Failure, Unspecified / Renal Dysfunction	1
1, 2	Recruiting	Treatment	High Blood Pressure (Hypertension)	1
1, 2	Terminated	Treatment	Cardiopulmonary Bypass / Heart Defects,Congenital	1
1, 2	Terminated	Treatment	Cardiorenal Syndrome	1
1, 2	Terminated	Treatment	High Blood Pressure (Hypertension)	1
2	Completed	Prevention	Acute Myocardial Infarction (AMI)	1
2	Completed	Prevention	Cardiopulmonary Bypass / Congestive Heart Failure (CHF) / Coronary Artery Bypass Graft Surgery Patients / Coronary Heart Disease (CHD) / Ischaemic Heart Diseases	1
2	Completed	Prevention	Renal Failure	1
2	Completed	Treatment	Acute Heart Failure (AHF)	1
2	Completed	Treatment	Congestive Heart Failure (CHF)	2
2	Completed	Treatment	Congestive Heart Failure (CHF) / Impaired Renal Function	1
2	Completed	Treatment	Heart Failure, Unspecified	1
2	Recruiting	Treatment	Diastolic Dysfunction / Type 2 Diabetes Mellitus	1
2	Terminated	Treatment	Heart Defects,Congenital	1
2	Terminated	Treatment	Heart Failure, Unspecified	1
3	Completed	Treatment	Congestive Heart Failure (CHF)	2
3	Completed	Treatment	Congestive Heart Failure (CHF) / Dyspnea, Paroxysma / Prophylaxis of cardiomyopathy	1
3	Completed	Treatment	Congestive Heart Failure (CHF) / Heart Decompensation	3
3	Completed	Treatment	Congestive Heart Failure (CHF) / Kidney Diseases / Prophylaxis of cardiomyopathy	1
3	Completed	Treatment	Congestive Heart Failure in Acute Coronary Syndrome / Symptomatic Decompensated Congestive Heart Failure	1
3	Completed	Treatment	Heart Decompensation	1
3	Terminated	Treatment	Heart Failure, Unspecified	1
3	Unknown Status	Prevention	Acute Renal Failure (ARF) / Cardiovascular Disease (CVD) / The Mortality Rate	1
3	Withdrawn	Treatment	Cardiopulmonary Bypass / Congestive Heart Failure (CHF) / Coronary Artery Bypass Graft Surgery Patients / Coronary Heart Disease (CHD) / Ischaemic Heart Diseases	1
4	Completed	Prevention	Pulmonary Hypertension (PH)	1
4	Completed	Treatment	Acute Decompensated Heart Failure (ADHF)	1
4	Completed	Treatment	Chronic Heart Failure (CHF) / Congestive Heart Failure (CHF)	1
4	Completed	Treatment	Congestive Heart Failure (CHF) / Prophylaxis of cardiomyopathy	1
4	Not Yet Recruiting	Basic Science	High Blood Pressure (Hypertension)	1
4	Recruiting	Other	BMI >30 kg/m2 / Cardiovascular Physiological Phenomena / Metabolism	1
4	Terminated	Treatment	Acute Heart Failure (AHF) / Cardiovascular Disease (CVD) / Congestive Heart Failure (CHF) / Diastolic Heart Failure / Heart Diseases / Heart Failure, Unspecified	1
4	Terminated	Treatment	Cardiorenal Syndrome / Congestive Heart Failure (CHF)	1
4	Terminated	Treatment	Cardiothoracic Surgery / Chronic Lung Diseases / Malignancies / Pulmonary Hypertension (PH)	1
4	Terminated	Treatment	Congestive Heart Failure (CHF)	2
4	Unknown Status	Supportive Care	Coronary Artery Disease	1
4	Withdrawn	Treatment	Congestive Heart Failure (CHF) / Dyspnea / Pulmonary Edemas	1
Not Available	Completed	Basic Science	High Blood Pressure (Hypertension)	1
Not Available	Completed	Diagnostic	Syncope	1
Not Available	Completed	Health Services Research	Congestive Heart Failure (CHF)	1
Not Available	Completed	Other	Healthy Volunteers	1
Not Available	Completed	Treatment	Congestive Cardiomyopathy	1
Not Available	Completed	Treatment	High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus	1
Not Available	Recruiting	Diagnostic	Meningococcal Infections / Severe Sepsis / Shock, Septic	1
Not Available	Recruiting	Treatment	Congenital Heart Disease (CHD) / Total Cavo-pulmonary Connection	1
Not Available	Withdrawn	Other	High Blood Pressure (Hypertension)	1
Not Available	Withdrawn	Treatment	Heart Decompensation / Heart Failure, Unspecified / Ventricular Dysfunction	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Janssen-Ortho Inc.
Scios Inc.

Dosage forms

Form	Route	Strength
Injection, powder, lyophilized, for solution	Intravenous	1.5 mg/5mL
Powder, for solution	Intravenous	1.5 mg

Prices

Unit description	Cost	Unit
Natrecor 1.5 mg vial	716.36USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5114923	No	1992-05-19	2014-05-19
CA1339210	No	1997-08-05	2014-08-05

Properties

State: Solid
Experimental Properties: Not Available

Taxonomy

Description: Not Available
Kingdom: Organic Compounds
Super Class: Organic Acids
Class: Carboxylic Acids and Derivatives
Sub Class: Amino Acids, Peptides, and Analogues
Direct Parent: Peptides
Alternative Parents: Not Available
Substituents: Not Available
Molecular Framework: Not Available
External Descriptors: Not Available

Targets

Details1. Atrial natriuretic peptide receptor 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Binder

General Function: Protein kinase activity
Specific Function: Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate ...
Gene Name: NPR1
Uniprot ID: P16066
Uniprot Name: Atrial natriuretic peptide receptor 1
Molecular Weight: 118918.11 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. Atrial natriuretic peptide receptor 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Transmembrane signaling receptor activity
Specific Function: Receptor for the C-type natriuretic peptide NPPC/CNP hormone. Has guanylate cyclase activity upon binding of its ligand. May play a role in the regulation of skeletal growth.
Gene Name: NPR2
Uniprot ID: P20594
Uniprot Name: Atrial natriuretic peptide receptor 2
Molecular Weight: 117020.97 Da

Details3. Atrial natriuretic peptide receptor 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Peptide hormone binding
Specific Function: Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP. May ...
Gene Name: NPR3
Uniprot ID: P17342
Uniprot Name: Atrial natriuretic peptide receptor 3
Molecular Weight: 59807.34 Da

Drug created on October 21, 2007 16:23 / Updated on November 02, 2018 06:07