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Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:32:45 UTC
HMDB IDHMDB15400
Secondary Accession NumbersNone
Metabolite Identification
Common NameHydralazine
DescriptionHydralazine is only found in individuals that have used or taken this drug. It is a direct-acting vasodilator that is used as an antihypertensive agent. [PubChem]Although the precise mechanism of action of hydralazine is not fully understood, the major effects are on the cardiovascular system. Hydralazine apparently lowers blood pressure by exerting a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle. It has also been suggested that cyclic 3',5'-adenosine monophosphate (cyclic AMP) mediates, at least partly, the relaxation of arterial smooth muscle by altering cellular calcium metabolism, which interferes with the calcium movements within the vascular smooth muscle that are responsible for initiating or maintaining the contractile state. In hypertensive patients, the hydralazine-induced decrease in blood pressure is accompanied by increased heart rate, cardiac output, and stroke volume, probably because of a reflex response to decreased peripheral resistance. The drug has no direct effect on the heart. Hydralazine may increase pulmonary arterial pressure, as well as coronary, splanchnic, cerebral, and renal blood flow. The preferential dilatation of arterioles, as compared to veins, minimizes postural hypotension and promotes the increase in cardiac output. Hydralazine usually increases renin activity in plasma, presumably as a result of increased secretion of renin by the renal juxtaglomerular cells in response to reflex sympathetic discharge. This increase in renin activity leads to the production of angiotensin II, which then causes stimulation of aldosterone and consequent sodium reabsorption. Tolerance to the antihypertensive effect of the drug develops during prolonged therapy, especially if a diuretic is not administered concurrently. In patients with CHF, hydralazine decreases systemic vascular resistance and increases cardiac output.
Structure
Thumb
Synonyms
ValueSource
(1Z)-1(2H)-Phthalazinone hydrazoneChEBI
(2H)-Phthalazinone hydrazoneChEBI
1-HydrazinophthalazineChEBI
1-PhthalazinylhydrazineChEBI
6-HydralazineChEBI
HidralazinaChEBI
HydralazinChEBI
HydralazinumChEBI
HydrallazineChEBI
HydrazinophthalazineChEBI
Hydrazone 1(2H)-phthalazinoneChEBI
HypophthalinChEBI
IdralazinaChEBI
Phthalazin-1-ylhydrazineChEBI
Hydralazine hydrochlorideHMDB
Chemical FormulaC8H8N4
Average Molecular Weight160.1759
Monoisotopic Molecular Weight160.074896276
IUPAC Name1-hydrazinylphthalazine
Traditional Namehydralazine
CAS Registry Number86-54-4
SMILES
NNC1=NN=CC2=CC=CC=C12
InChI Identifier
InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
InChI KeyInChIKey=RPTUSVTUFVMDQK-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phthalazines. These are compounds containing a phthalazine moiety, which consists of a benzene ring fused to a pyridazine, forming a 2,3-benzodiazine skeleton.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassPhthalazines
Direct ParentPhthalazines
Alternative Parents
Substituents
  • Phthalazine
  • Aminopyridazine
  • Imidolactam
  • Benzenoid
  • Pyridazine
  • Heteroaromatic compound
  • Azacycle
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Hydrazine derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antihypertensive Agents
  • Vasodilator Agents
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point172 - 173 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.61e+00 g/LNot Available
LogP0.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.61 mg/mLALOGPS
logP0.66ALOGPS
logP0.75ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)17.69ChemAxon
pKa (Strongest Basic)6.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area63.83 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity50.23 m3·mol-1ChemAxon
Polarizability16.06 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01275
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01275
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01275
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3511
KEGG Compound IDC07040
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkHydralazine
NuGOwiki LinkHMDB15400
Metagene LinkHMDB15400
METLIN IDNot Available
PubChem Compound3637
PDB IDHLZ
ChEBI ID5775
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kandler MR, Mah GT, Tejani AM, Stabler SN: Hydralazine for essential hypertension. Cochrane Database Syst Rev. 2010 Aug 4;(8):CD004934. doi: 10.1002/14651858.CD004934.pub3. [20687078 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Gene Name:
P4HA1
Uniprot ID:
P13674
Molecular weight:
60966.645
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Knowles HJ, Tian YM, Mole DR, Harris AL: Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases. Circ Res. 2004 Jul 23;95(2):162-9. Epub 2004 Jun 10. [15192023 ]
  3. Murad S, Tajima S, Pinnell SR: A paradoxical effect of hydralazine on prolyl and lysyl hydroxylase activities in cultured human skin fibroblasts. Arch Biochem Biophys. 1985 Sep;241(2):356-63. [2994564 ]
  4. Chen KH, Paz MA, Gallop PM: Collagen prolyl hydroxylation in WI-38 fibroblast cultures: action of hydralazine. In Vitro. 1977 Jan;13(1):49-54. [856725 ]
General function:
Involved in copper ion binding
Specific function:
Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis.
Gene Name:
AOC3
Uniprot ID:
Q16853
Molecular weight:
84621.27
References
  1. Claud P, Padovani P, Guichard JP, Artur Y, Laine R: Involvement of semicarbazide-sensitive amine oxidase in tresperimus metabolism in human and in rat. Drug Metab Dispos. 2001 May;29(5):735-41. [11302941 ]
  2. Vidrio H, Medina M, Gonzalez-Romo P, Lorenzana-Jimenez M, Diaz-Arista P, Baeza A: Semicarbazide-sensitive amine oxidase substrates potentiate hydralazine hypotension: possible role of hydrogen peroxide. J Pharmacol Exp Ther. 2003 Nov;307(2):497-504. Epub 2003 Sep 11. [12970383 ]
  3. Vidrio H: Semicarbazide-sensitive amine oxidase: role in the vasculature and vasodilation after in situ inhibition. Auton Autacoid Pharmacol. 2003 Oct-Dec;23(5-6):275-83. [15255812 ]
  4. Vidrio H, Medina M: 2-bromoethylamine, a suicide inhibitor of semicarbazide-sensitive amine oxidase, increases hydralazine hypotension in rats. J Cardiovasc Pharmacol. 2005 Sep;46(3):316-24. [16116337 ]
  5. Vidrio H, Medina M: Hypotensive effect of hydroxylamine, an endogenous nitric oxide donor and SSAO inhibitor. J Neural Transm. 2007;114(6):863-5. Epub 2007 Mar 26. [17385063 ]
  6. Gronvall JL, Garpenstrand H, Oreland L, Ekblom J: An autoradiographic method of visualising semicarbazide-sensitive amine oxidase activity in mouse tissue sections. Neurobiology (Bp). 2000;8(2):167-77. [11061213 ]
  7. Gronvall JL, Garpenstrand H, Oreland L, Ekblom J: Autoradiographic imaging of formaldehyde adducts in mice: possible relevance for vascular damage in diabetes. Life Sci. 1998;63(9):759-68. [9740313 ]
  8. Lizcano JM, Fernandez de Arriba A, Tipton KF, Unzeta M: Inhibition of bovine lung semicarbazide-sensitive amine oxidase (SSAO) by some hydrazine derivatives. Biochem Pharmacol. 1996 Jul 26;52(2):187-95. [8694842 ]
  9. Lyles GA, McDougall SA: The enhanced daily excretion of urinary methylamine in rats treated with semicarbazide or hydralazine may be related to the inhibition of semicarbazide-sensitive amine oxidase activities. J Pharm Pharmacol. 1989 Feb;41(2):97-100. [2568436 ]
  10. Barrand MA, Callingham BA: The interaction of hydralazine with a semicarbazide-sensitive amine oxidase in brown adipose tissue of the rat. Its use as a radioactive ligand for the enzyme. Biochem J. 1985 Dec 1;232(2):415-23. [4091799 ]
  11. Barrand MA, Fox SA: Amine oxidase activities in brown adipose tissue of the rat: identification of semicarbazide-sensitive (clorgyline-resistant) activity at the fat cell membrane. J Pharm Pharmacol. 1984 Oct;36(10):652-8. [6150080 ]
General function:
Involved in monooxygenase 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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. Epub 2009 Nov 24. [19934256 ]