Identification

Name
Nitroprusside
Accession Number
DB00325  (APRD01143)
Type
Small Molecule
Groups
Approved, Investigational
Description

Nitroprusside serves as a source of nitric oxide, a potent peripheral vasodilator that affects both arterioles and venules (venules more than arterioles). Nitroprusside is often administered intravenously to patients who are experiencing a hypertensive emergency.

Structure
Thumb
Synonyms
  • Nitroferricyanide
Product Ingredients
IngredientUNIICASInChI Key
Sodium nitroprussideEAO03PE1TC13755-38-9OIRZWVYIQXBRFC-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NipridePowder, for solution50 mgIntravenousHospira, Inc.1975-12-312011-08-05Canada
NiprideSolution25 mgIntravenousPfizer2011-05-17Not applicableCanada
Nipride RtuInjection, solution0.5 mg/1mLIntravenousExela Pharma Sciences, LLC2017-03-20Not applicableUs
Nipride RtuInjection, solution0.2 mg/1mLIntravenousExela Pharma Sciences, LLC2018-07-20Not applicableUs
Nipride RtuInjection, solution0.2 mg/1mLIntravenousExela Pharma Sciences, LLC2018-02-09Not applicableUs
Sodium Nitroprusside for InjectionSolution25 mgIntravenousSterimax IncNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NitropressInjection, solution, concentrate50 mg/2mLIntravenousValeant Pharmaceuticals North America2013-12-01Not applicableUs
NitropressInjection, solution, concentrate50 mg/2mLIntravenousMarathon Pharmaceuticals2013-12-012016-05-31Us
NitropressInjection, solution, concentrate50 mg/2mLIntravenousHospira, Inc.2005-06-072015-07-01Us
Sodium NitroprussideInjection, solution, concentrate25 mg/1mLIntravenousSomerset Therapeutics, Llc2018-08-17Not applicableUs
Sodium NitroprussideInjection, solution, concentrate50 mg/2mLIntravenousAkorn2017-05-04Not applicableUs
Sodium NitroprussideInjection, solution, concentrate25 mg/1mLIntravenousSagent Pharmaceuticals2017-12-01Not applicableUs
Sodium NitroprussideInjection25 mg/1mLIntravenousNexus Pharmaceuticals Inc2017-05-29Not applicableUs
Sodium nitroprussideInjection, solution, concentrate25 mg/1mLIntravenousMylan Institutional2018-08-10Not applicableUs
Sodium NitroprussideInjection50 mg/2mLIntravenousMicro Labs Limited2017-12-30Not applicableUs
Sodium nitroprussideInjection25 mg/1mLIntravenousAmneal Biosciences Llc2017-11-07Not applicableUs
Categories
UNII
169D1260KM
CAS number
15078-28-1
Weight
Average: 215.938
Monoisotopic: 215.948300785
Chemical Formula
C5FeN6O
InChI Key
ASPOIVQEUUCDQT-UHFFFAOYSA-N
InChI
InChI=1S/5CN.Fe.NO/c5*1-2;;1-2/q;;;;;2*-1
IUPAC Name
pentacyano(nitroso)irondiuide
SMILES
O=N[Fe--](C#N)(C#N)(C#N)(C#N)C#N

Pharmacology

Indication

For immediate reduction of blood pressure of patients in hypertensive crises, reduce bleeding during surgery, and for the treatment of acute congestive heart failure

Associated Conditions
Pharmacodynamics

Nitroprusside a powerful vasodilator relaxes the vascular smooth muscle and produce consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries.

Mechanism of action

One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN- ions; methemoglobin, obtained from hemoglobin, can sequester cyanide as cyanmethemoglobin; thiosulfate reacts with cyanide to produce thiocyanate; thiocyanate is eliminated in the urine; cyanide not otherwise removed binds to cytochromes. Cyanide ion is normally found in serum; it is derived from dietary substrates and from tobacco smoke. Cyanide binds avidly (but reversibly) to ferric ion (Fe+++), most body stores of which are found in erythrocyte methemoglobin (metHgb) and in mitochondrial cytochromes. When CN is infused or generated within the bloodstream, essentially all of it is bound to methemoglobin until intraerythrocytic methemoglobin has been saturated. Once activated to NO, it activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP stimulates calcium movement from the cytoplasm to the endoplasmic reticulum and reduces calcium available to bind with calmodulin. This eventually leads to vascular smooth muscle relaxation and vessel dilatation.

TargetActionsOrganism
AAtrial natriuretic peptide receptor 1
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized by reaction with hemoglobin to produce cyanmethemoglobin and cynide ions

Route of elimination

One molecule of sodium nitroprusside is metabolized by combination with hemoglobin to produce one molecule of cyanmethemoglobin and four CN¯ ions, thiosulfate reacts with cyanide to produce thiocyanate, thiocyanate is eliminated in the urine.

Half life

Approximately 2 minutes

Clearance
Not Available
Toxicity

Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity or as thiocyanate toxicity. The acute intravenous mean lethal doses (LD50) of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
3-Aza-2,3-Dihydrogeranyl DiphosphateNitroprusside can cause a decrease in the absorption of 3-Aza-2,3-Dihydrogeranyl Diphosphate resulting in a reduced serum concentration and potentially a decrease in efficacy.
AbacavirNitroprusside may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Nitroprusside which could result in a higher serum level.
AcebutololNitroprusside may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Nitroprusside can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Nitroprusside can be decreased when used in combination with Acemetacin.
AcetaminophenThe risk or severity of methemoglobinemia can be increased when Acetaminophen is combined with Nitroprusside.
AcetarsolNitroprusside may decrease the excretion rate of Acetarsol which could result in a higher serum level.
Acetylsalicylic acidThe therapeutic efficacy of Nitroprusside can be decreased when used in combination with Acetylsalicylic acid.
AclidiniumNitroprusside may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014470
KEGG Compound
C07269
PubChem Compound
11963622
PubChem Substance
46508965
ChemSpider
21607452
BindingDB
50377921
ChEBI
7596
ChEMBL
CHEMBL2097081
Therapeutic Targets Database
DNC001351
PharmGKB
PA451406
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nitroprusside
ATC Codes
C02DD01 — Nitroprusside
AHFS Codes
  • 24:08.20 — Direct Vasodilators
MSDS
Download (79 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAging1
1CompletedBasic ScienceCardiovascular Disease (CVD) / Cardiovascular Risk Factors / Vasoconstriction1
1CompletedBasic ScienceSarcopenia2
1CompletedBasic ScienceSchizophrenic Disorders1
1Not Yet RecruitingBasic ScienceCardiovascular Disease (CVD) / Cardiovascular Risk Factors / Vasoconstriction1
1TerminatedOtherInflammatory Reaction1
1Unknown StatusTreatmentAcute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS) / Arterial hypoxia / Respiratory Failure / Sodium Nitroprusside1
2CompletedTreatmentArterial Hypotension1
2CompletedTreatmentCerebral Oxygenation1
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentSchizophrenic Disorders2
2Not Yet RecruitingTreatmentAnemias1
2RecruitingPreventionStress Disorders, Post-Traumatic1
2RecruitingTreatmentDepression1
2TerminatedDiagnosticHyperlipidemias1
2, 3CompletedTreatmentMyocardial Infarction1
3CompletedTreatmentHeart Failure, Unspecified / High Blood Pressure (Hypertension)1
3CompletedTreatmentHigh Blood Pressure (Hypertension)1
4Not Yet RecruitingTreatmentAcute Heart Failure (AHF)1
4TerminatedPreventionMyocardial Infarction1
4Unknown StatusScreeningNitroprusside / Thyroid Hormones1
Not AvailableCompletedNot AvailableCancers / Endothelial Dysfunction / High Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedNot AvailableHypotension, Controlled1
Not AvailableCompletedNot AvailableIntracerebral Hemorrhage / Subarachnoid Hemorrhage1
Not AvailableCompletedNot AvailableLeiomyomas1
Not AvailableCompletedBasic ScienceHeart Diseases / Heart Failure, Unspecified / Vasodilatation1
Not AvailableCompletedBasic ScienceHeart Diseases / Vasodilation1
Not AvailableCompletedTreatmentCVA (Cerebrovascular Accident) / Intracerebral Hemorrhage / Intracranial Hemorrhages1
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus1
Not AvailableTerminatedBasic ScienceProphylaxis of cardiomyopathy / Stress-induced (Takotsubo) Cardiomyopathy1
Not AvailableUnknown StatusNot AvailableDiabetes Mellitus (DM)1

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
  • Abbott laboratories
  • Abbott laboratories pharmaceutical products div
  • Hospira inc
  • Abraxis pharmaceutical products
  • Baxter healthcare corp anesthesia and critical care
  • Teva parenteral medicines inc
Packagers
  • Baxter International Inc.
  • Hospira Inc.
  • Physicians Total Care Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous50 mg
Injection, solutionIntravenous0.2 mg/1mL
Injection, solutionIntravenous0.5 mg/1mL
Injection, solution, concentrateIntravenous50 mg/2mL
InjectionIntravenous25 mg/1mL
InjectionIntravenous50 mg/2mL
Injection, solution, concentrateIntravenous25 mg/1mL
SolutionIntravenous25 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP0.071ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area148.38 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity39.44 m3·mol-1ChemAxon
Polarizability16.52 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8308
Blood Brain Barrier+0.9314
Caco-2 permeable-0.5269
P-glycoprotein substrateNon-substrate0.8966
P-glycoprotein inhibitor INon-inhibitor0.919
P-glycoprotein inhibitor IINon-inhibitor0.9767
Renal organic cation transporterNon-inhibitor0.9109
CYP450 2C9 substrateNon-substrate0.8573
CYP450 2D6 substrateNon-substrate0.8353
CYP450 3A4 substrateNon-substrate0.6675
CYP450 1A2 substrateNon-inhibitor0.6719
CYP450 2C9 inhibitorNon-inhibitor0.8599
CYP450 2D6 inhibitorNon-inhibitor0.9186
CYP450 2C19 inhibitorNon-inhibitor0.8218
CYP450 3A4 inhibitorNon-inhibitor0.9763
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9583
Ames testNon AMES toxic0.5204
CarcinogenicityCarcinogens 0.6595
BiodegradationNot ready biodegradable0.5759
Rat acute toxicity2.9543 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9345
hERG inhibition (predictor II)Non-inhibitor0.9596
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as organic transition metal salts. These are organic salt compounds containing a transition metal atom in its ionic form.
Kingdom
Organic compounds
Super Class
Organic salts
Class
Organic metal salts
Sub Class
Organic transition metal salts
Direct Parent
Organic transition metal salts
Alternative Parents
Organotransition metal compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Organic anions
Substituents
Organic transition metal salt / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organonitrogen compound / Organometallic compound / Organic transition metal moeity / Organic anion
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
iron coordination entity (CHEBI:7596)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Fortin Y, De Lean A: Role of cyclic GMP and calcineurin in homologous and heterologous desensitization of natriuretic peptide receptor-A. Can J Physiol Pharmacol. 2006 May;84(5):539-46. [PubMed:16902599]
  2. Madhani M, Okorie M, Hobbs AJ, MacAllister RJ: Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo. Br J Pharmacol. 2006 Nov;149(6):797-801. Epub 2006 Oct 3. [PubMed:17016498]
  3. Steinmetz M, Potthast R, Sabrane K, Kuhn M: Diverging vasorelaxing effects of C-type natriuretic peptide in renal resistance arteries and aortas of GC-A-deficient mice. Regul Pept. 2004 Jun 15;119(1-2):31-7. [PubMed:15093694]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:25