Identification

Name
Nesiritide
Accession Number
DB04899
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Description

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
Db04899
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
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NatrecorPowder, for solution1.5 mgIntravenousJanssen Pharmaceuticals2008-02-052012-08-01Canada
NatrecorInjection, powder, lyophilized, for solution1.5 mg/5mLIntravenousScios, Inc.2001-08-01Not applicableUs
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
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.

TargetActionsOrganism
UAtrial natriuretic peptide receptor 1
binder
Human
UAtrial natriuretic peptide receptor 2Not AvailableHuman
UAtrial natriuretic peptide receptor 3Not AvailableHuman
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
DrugInteraction
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Nesiritide.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Nesiritide.
AliskirenThe risk or severity of adverse effects can be increased when Nesiritide is combined with Aliskiren.
AmifostineThe risk or severity of adverse effects can be increased when Amifostine is combined with Nesiritide.
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Nesiritide.
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Nesiritide.
AmlodipineThe risk or severity of adverse effects can be increased when Amlodipine is combined with Nesiritide.
AmobarbitalAmobarbital may increase the hypotensive activities of Nesiritide.
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Nesiritide.
Amyl NitriteThe risk or severity of adverse effects can be increased when Amyl Nitrite is combined with Nesiritide.
Food Interactions
Not Available

References

General References
  1. 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]
  2. Maisel AS: Nesiritide: a new therapy for the treatment of heart failure. Cardiovasc Toxicol. 2003;3(1):37-42. [PubMed:12668889]
  3. Vichiendilokkul A, Tran A, Racine E: Nesiritide: a novel approach for acute heart failure. Ann Pharmacother. 2003 Feb;37(2):247-58. [PubMed:12549957]
  4. Cheng JW: Nesiritide: review of clinical pharmacology and role in heart failure management. Heart Dis. 2002 May-Jun;4(3):199-203. [PubMed:12028606]
  5. 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
PhaseStatusPurposeConditionsCount
0WithdrawnOtherBMI >30 kg/m2 / Hyperinsulinemia1
1CompletedBasic ScienceBMI >30 kg/m2 / Cardiovascular Disease (CVD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
1TerminatedBasic ScienceCongestive Heart Failure (CHF) / Renal Dysfunction1
1, 2CompletedBasic ScienceAsymptomatic Systolic Dysfunction / Heart Failure, Unspecified1
1, 2CompletedBasic ScienceCongestive Heart Failure (CHF)1
1, 2CompletedBasic ScienceLeft Ventricular Diastolic Dysfunction1
1, 2CompletedPreventionCongestive Heart Failure (CHF)1
1, 2CompletedTreatmentAcute Renal Failure (ARF)1
1, 2CompletedTreatmentCongestive Heart Failure (CHF) / Prophylaxis of cardiomyopathy1
1, 2CompletedTreatmentDiastolic Heart Failure1
1, 2Enrolling by InvitationTreatmentHeart Failure, Unspecified / Renal Dysfunction1
1, 2RecruitingTreatmentHigh Blood Pressure (Hypertension)1
1, 2TerminatedTreatmentCardiopulmonary Bypass / Heart Defects,Congenital1
1, 2TerminatedTreatmentCardiorenal Syndrome1
1, 2TerminatedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedPreventionAcute Myocardial Infarction (AMI)1
2CompletedPreventionCardiopulmonary Bypass / Congestive Heart Failure (CHF) / Coronary Artery Bypass Grafting (CABG) Surgery / Coronary Artery Bypass Surgery / Coronary Heart Disease (CHD) / Ischaemic Heart Diseases1
2CompletedPreventionRenal Failure1
2CompletedTreatmentAcute Heart Failure (AHF)1
2CompletedTreatmentCongestive Heart Failure (CHF)2
2CompletedTreatmentCongestive Heart Failure (CHF) / Impaired Renal Function1
2CompletedTreatmentHeart Failure, Unspecified1
2TerminatedTreatmentHeart Defects,Congenital1
2TerminatedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentCongestive Heart Failure (CHF)2
3CompletedTreatmentCongestive Heart Failure (CHF) / Dyspnea, Paroxysma / Prophylaxis of cardiomyopathy1
3CompletedTreatmentCongestive Heart Failure (CHF) / Heart Decompensation3
3CompletedTreatmentCongestive Heart Failure (CHF) / Kidney Diseases / Prophylaxis of cardiomyopathy1
3CompletedTreatmentCongestive Heart Failure in Acute Coronary Syndrome / Symptomatic Decompensated Congestive Heart Failure1
3CompletedTreatmentHeart Decompensation1
3TerminatedTreatmentHeart Failure, Unspecified1
3Unknown StatusPreventionAcute Renal Failure (ARF) / Cardiovascular Disease (CVD) / Mortality1
3WithdrawnTreatmentCardiopulmonary Bypass / Congestive Heart Failure (CHF) / Coronary Artery Bypass Grafting (CABG) Surgery / Coronary Artery Bypass Surgery / Coronary Heart Disease (CHD) / Ischaemic Heart Diseases1
4CompletedPreventionPulmonary Hypertension (PH)1
4CompletedTreatmentAcute Decompensated Heart Failure (ADHF)1
4CompletedTreatmentChronic Heart Failure (CHF) / Congestive Heart Failure (CHF)1
4CompletedTreatmentCongestive Heart Failure (CHF) / Prophylaxis of cardiomyopathy1
4RecruitingOtherBMI >30 kg/m2 / Cardiovascular Physiological Phenomena / Metabolism1
4TerminatedTreatmentAcute Heart Failure (AHF) / Cardiovascular Disease (CVD) / Congestive Heart Failure (CHF) / Diastolic Heart Failure / Heart Diseases / Heart Failure, Unspecified1
4TerminatedTreatmentCancers / Cardiothoracic Surgery / Chronic Lung Diseases / Pulmonary Hypertension (PH)1
4TerminatedTreatmentCardiorenal Syndrome / Congestive Heart Failure (CHF)1
4TerminatedTreatmentCongestive Heart Failure (CHF)2
4Unknown StatusSupportive CareCoronary Artery Disease1
4WithdrawnTreatmentCongestive Heart Failure (CHF) / Dyspnea / Pulmonary Edemas1
Not AvailableCompletedBasic ScienceHigh Blood Pressure (Hypertension)1
Not AvailableCompletedDiagnosticSyncope1
Not AvailableCompletedHealth Services ResearchCongestive Heart Failure (CHF)1
Not AvailableCompletedOtherHealthy Volunteers1
Not AvailableCompletedTreatmentCongestive Cardiomyopathy1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
Not AvailableRecruitingDiagnosticMeningococcal Infections / Severe Sepsis / Shock, Septic1
Not AvailableRecruitingTreatmentCongenital Heart Disease (CHD) / Total Cavo-pulmonary Connection1
Not AvailableWithdrawnOtherHigh Blood Pressure (Hypertension)1
Not AvailableWithdrawnTreatmentHeart Decompensation / Heart Failure, Unspecified / Ventricular Dysfunction1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Janssen-Ortho Inc.
  • Scios Inc.
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous1.5 mg/5mL
Powder, for solutionIntravenous1.5 mg
Prices
Unit descriptionCostUnit
Natrecor 1.5 mg vial716.36USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5114923No1994-05-192014-05-19Us
CA1339210No1997-08-052014-08-05Canada

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

Kind
Protein
Organism
Human
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
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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 August 02, 2018 05:28