Identification

Name
Hydralazine
Accession Number
DB01275
Type
Small Molecule
Groups
Approved
Description

A direct-acting vasodilator that is used as an antihypertensive agent.

Structure
Thumb
Synonyms
  • (1Z)-1(2H)-Phthalazinone hydrazone
  • (2H)-Phthalazinone hydrazone
  • 1-Hydrazinophthalazine
  • 1-Phthalazinylhydrazine
  • 6-Hydralazine
  • Hidralazina
  • Hydralazin
  • Hydralazinum
  • Hydrallazine
  • Hydrazinophthalazine
  • Hydrazone 1(2H)-phthalazinone
  • Hypophthalin
  • Idralazina
  • Phthalazin-1-ylhydrazine
Product Ingredients
IngredientUNIICASInChI Key
Hydralazine hydrochlorideFD171B778Y304-20-1ZUXNZUWOTSUBMN-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ApresolineSolution20 mgIntravenousSterimax Inc1992-12-31Not applicableCanada
Apresoline hydrochlorideTablet, coated100 mg/1OralUNSPECIFIED2006-05-112010-10-13Us
Apresoline hydrochlorideTablet, coated10 mg/1OralUNSPECIFIED2006-05-112010-10-13Us
Apresoline hydrochlorideTablet, coated50 mg/1OralUNSPECIFIED2006-05-112010-10-13Us
Apresoline hydrochlorideTablet, coated50 mg/1OralPhysicians Total Care, Inc.1995-02-172010-10-07Us
Apresoline hydrochlorideTablet, coated25 mg/1OralUNSPECIFIED2006-05-112010-10-13Us
Apresoline Tablets, 10mgTablet10 mgOralSterimax Inc1952-12-312005-07-22Canada
Apresoline Tablets, 25mgTablet25 mgOralSterimax Inc1952-12-312005-07-19Canada
Apresoline Tablets, 50mgTablet50 mgOralSterimax Inc1952-12-312005-07-19Canada
HydrALAZINE HydrochlorideTablet10 mg/1OralInvaGen Pharmaceuticals, Inc.,2008-12-22Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-hydralazineTablet25 mgOralApotex Corporation1991-12-31Not applicableCanada
Apo-hydralazineTablet50 mgOralApotex Corporation1991-12-31Not applicableCanada
Apo-hydralazineTablet10 mgOralApotex Corporation1990-12-31Not applicableCanada
HydralazineTablet100 mg/1OralNivagen Pharmaceuticals, Inc.2017-02-15Not applicableUs
HydralazineTablet25 mg/1OralCardinal Health2009-09-14Not applicableUs
HydralazineTablet50 mg/1OralNivagen Pharmaceuticals, Inc.2017-02-15Not applicableUs
HydralazineTablet25 mg/1OralNivagen Pharmaceuticals, Inc.2017-02-15Not applicableUs
HydralazineTablet25 mg/1OralREMEDYREPACK INC.2018-10-24Not applicableUs
HydralazineTablet50 mg/1OralCardinal Health2009-09-14Not applicableUs
Hydralazine HydrchlorideInjection20 mg/1mLIntramuscular; IntravenousGeneral Injectables and Vaccines, Inc.2018-09-07Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BiDilHydralazine hydrochloride (37.5 mg/1) + Isosorbide dinitrate (20 mg/1)Tablet, film coatedOralArbor Pharmaceuticals2012-12-05Not applicableUs24338 01020180907 15195 ecm0g8
BiDilHydralazine hydrochloride (37.5 mg/1) + Isosorbide dinitrate (20 mg/1)Tablet, film coatedOralArbor Pharmaceuticals2005-06-232015-12-31Us12948 0001 12 nlmimage10 2f131798
BiDilHydralazine hydrochloride (37.5 mg/1) + Isosorbide dinitrate (20 mg/1)Tablet, film coatedOralRemedy Repack2013-10-082013-10-09Us
Hydralazine HCl and HydrochlorothiazideHydralazine hydrochloride (50 mg/1) + Hydrochlorothiazide (50 mg/1)CapsuleOralPar Pharmaceutical1985-10-212009-10-29Us
Hydralazine HCl and HydrochlorothiazideHydralazine hydrochloride (25 mg/1) + Hydrochlorothiazide (25 mg/1)CapsuleOralPar Pharmaceutical1985-10-212009-10-29Us
Hydralazine HCl and HydrochlorothiazideHydralazine hydrochloride (100 mg/1) + Hydrochlorothiazide (50 mg/1)CapsuleOralPar Pharmaceutical1985-10-212009-10-29Us
Ser-Ap-EsHydralazine hydrochloride (25 mg/1) + Hydrochlorothiazide (15 mg/1) + Reserpine (0.1 mg/1)Tablet, coatedOralNovartis2006-04-07Not applicableUs
Ser-AP-ES TabHydralazine hydrochloride (25 mg) + Hydrochlorothiazide (15 mg) + Reserpine (0.1 mg)TabletOralNovartis1960-12-312000-08-02Canada
International/Other Brands
Alphapress (Alphapharm) / Aprezin (Johnson) / Cesoline W (Pharmasant) / Cesoline Y (Pharmasant) / Diazide (The Central) / Hidral (Biocontrol) / Pressfall (Nisshin Seiyaku) / Serpathiazide (Washington)
Categories
UNII
26NAK24LS8
CAS number
86-54-4
Weight
Average: 160.1759
Monoisotopic: 160.074896276
Chemical Formula
C8H8N4
InChI Key
RPTUSVTUFVMDQK-UHFFFAOYSA-N
InChI
InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
IUPAC Name
1-hydrazinylphthalazine
SMILES
NNC1=NN=CC2=CC=CC=C12

Pharmacology

Indication

For the treatment of essential hypertension, alone or as an adjunct. Also for the management of severe hypertension when the drug cannot be given orally or when blood pressure must be lowered immediately, congestive heart failure (in combination with cardiac glycosides and diuretics and/or with isosorbide dinitrate), and hypertension secondary to pre-eclampsia/eclampsia.

Associated Conditions
Pharmacodynamics

A vasodilator, hydralazine works by relaxing blood vessels (arterioles more than venules) and increasing the supply of blood and oxygen to the heart while reducing its workload. It also functions as an antioxidant. It inhibits membrane-bound enzymes that form reactive oxygen species, such as superoxides. Excessive superoxide counteracts NO-induced vasodilation. It is commonly used in the condition of pregnancy called preeclampsia.

Mechanism of action

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.

TargetActionsOrganism
AMembrane primary amine oxidase
inhibitor
Human
UProlyl 4-hydroxylase subunit alpha-1
inhibitor
Human
Absorption

Hydralazine is rapidly and extensively absorbed (up to 90%) from the gastrointestinal tract and undergoes extensive first-pass metabolism by genetic polymorphic acetylation. Oral bioavailability of hydralazine is dependent upon acetylator phenotype. Bioavailability is approximately 31% in slow acetylators and 10% in fast acetylators.

Volume of distribution
Not Available
Protein binding

87%

Metabolism

Hydralazine, when administered orally, undergoes extensive first-pass metabolism by genetic polymorphic acetylation, which is responsible for a threefold range of oral bioavailability. Intravenously administered hydralazine does not undergo first-pass metabolism and, therefore, is not affected by acetylator phenotype. After the drug reaches the systemic circulation, it is combined with endogenous aldehydes and ketones, including pyruvic acid, to form hydrazone metabolites. The active metabolites, hydralazine acetonide hydrazone and hydralazine pyruvate hydrazone, are equipotent with the parent, hydralazine.

Route of elimination

Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine.

Half life

3 to 7 hours

Clearance
Not Available
Toxicity

Oral LD50 in rats: 173 and 187 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Arylamine N-acetyltransferase 1NAT1*14ANot AvailableG > A | T > A | C > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 1NAT1*14BNot AvailableG > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 1NAT1*15Not AvailableC > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 1NAT1*17Not AvailableC > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 1NAT1*19ANot AvailableC > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 1NAT1*19BNot AvailableC > T | C > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 1NAT1*22Not AvailableA > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5ANot AvailableT > C | C > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5BNot AvailableT > C | C > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5CNot AvailableT > C | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5DNot AvailableT > CADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5ENot AvailableT > C | G > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5FNot AvailableT > C | C > T | C > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5GNot AvailableT > C | C > T | C > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5HNot AvailableT > C | C > T | A > G | S287 FrameshiftADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5INot AvailableT > C | C > T | A > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*5JNot AvailableT > C | C > T | G > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*6ANot AvailableG > A | C > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*6BNot AvailableG > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*6CNot AvailableG > A | C > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*6DNot AvailableG > A | C > T | T > CADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*6ENot AvailableG > A | C > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*7ANot AvailableG > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*7BNot AvailableG > A | C > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*10Not AvailableG > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*12DNot AvailableG > A | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14ANot AvailableG > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14BNot AvailableG > A | C > TADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14CNot AvailableG > A | T > C | C > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14DNot AvailableG > A | C > T | G > AADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14ENot AvailableG > A | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14FNot AvailableG > A | T > C | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*14GNot AvailableG > A | C > T | A > GADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*17Not AvailableA > CADR InferredAssociated with systemic lupus erythematosus.Details
Arylamine N-acetyltransferase 2NAT2*19Not AvailableC > TADR InferredAssociated with systemic lupus erythematosus.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Hydralazine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Hydralazine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Hydralazine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Hydralazine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Hydralazine.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Hydralazine.
AbacavirAbacavir may decrease the excretion rate of Hydralazine which could result in a higher serum level.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Hydralazine.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Hydralazine.
AcarboseAcarbose may decrease the excretion rate of Hydralazine which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,484,029.

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. [PubMed:20687078]
External Links
Human Metabolome Database
HMDB0015400
KEGG Drug
D08044
KEGG Compound
C07040
PubChem Compound
3637
PubChem Substance
46507533
ChemSpider
3511
BindingDB
81461
ChEBI
5775
ChEMBL
CHEMBL276832
Therapeutic Targets Database
DAP000728
PharmGKB
PA449894
HET
HLZ
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Hydralazine
ATC Codes
C02DB02 — HydralazineC02LG02 — Hydralazine and diuretics
AHFS Codes
  • 24:08.20 — Direct Vasodilators
PDB Entries
3ltw
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingBasic SciencePolycystic Kidney Diseases1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHeart Failure, Unspecified1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1CompletedTreatmentLung Cancers1
1, 2WithdrawnHealth Services ResearchCancer, Breast1
1, 2WithdrawnHealth Services ResearchRectal Carcinoma1
2CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
2CompletedTreatmentCervical Cancers1
2CompletedTreatmentHydralazine Adverse Reaction / Pre-eclampsia Superimposed Pre-existing Hypertension / Pregnancy associated hypertension / Prophylaxis of preeclampsia1
2CompletedTreatmentIntracerebral Hemorrhage1
2CompletedTreatmentRefractory Solid Tumors1
2RecruitingTreatmentIntracerebral Hemorrhage1
2TerminatedTreatmentLocally Advanced Breast Cancer (LABC)1
2, 3CompletedTreatmentCardiac Failure / Congestive Heart Failure (CHF) / Heart Failure, Unspecified1
3Active Not RecruitingTreatmentAcute Heart Failure (AHF) / Symptomatic left ventricular ejection fraction ≤ 35% Chronic heart failure1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedTreatmentPregnancy associated hypertension1
3Not Yet RecruitingTreatmentCervical Cancers1
3Unknown StatusTreatmentCancer of the Ovary1
3Unknown StatusTreatmentCardio-Renal Syndrome1
3Unknown StatusTreatmentRecurrent, IV-B Cervical cancer1
4CompletedTreatmentAcne Vulgaris1
4CompletedTreatmentCongestive Heart Failure (CHF)1
4CompletedTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentStage II Hypertension1
4RecruitingPreventionChronic Hemodialysis (ESRD)1
4RecruitingTreatmentDiabetes Mellitus (DM) / Heart Failure, Unspecified1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedBasic ScienceHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentCVA (Cerebrovascular Accident) / Intracerebral Hemorrhage / Intracranial Hemorrhages1
Not AvailableRecruitingNot AvailableHeart Failure, Unspecified1
Not AvailableTerminatedTreatmentTreatment Induced Hypertension1
Not AvailableWithdrawnTreatmentHigh Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • American Regent
  • Amerisource Health Services Corp.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • Camber Pharmaceuticals Inc.
  • Cardinal Health
  • Caremark LLC
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • General Injectables and Vaccines Inc.
  • Glenmark Generics Ltd.
  • Goldline Laboratories Inc.
  • Heartland Repack Services LLC
  • Heritage Pharmaceuticals
  • Hetero Drugs Ltd.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Luitpold Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
SolutionIntravenous20 mg
Tablet, coatedOral10 mg/1
Tablet, coatedOral100 mg/1
Tablet, coatedOral25 mg/1
Tablet, coatedOral50 mg/1
Tablet, film coatedOral
CapsuleOral
InjectionIntramuscular; Intravenous20 mg/1mL
Injection, solutionIntramuscular; Intravascular20 mg/1mL
Injection, solutionIntramuscular; Intravenous20 mg/1mL
TabletOral10 mg/1
TabletOral100 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
TabletOral10 mg
TabletOral25 mg
TabletOral50 mg
Tablet, coatedOral
TabletOral
Prices
Unit descriptionCostUnit
Hydralazine 20 mg/ml vial18.0USD ml
Hydralazine 100 mg tablet1.65USD tablet
Hydralazine-HCTZ 50-50 mg capsule1.2USD capsule
HydrALAZINE HCl 100 mg tablet1.05USD tablet
Hydralazine-HCTZ 25-25 mg capsule0.81USD capsule
Hydralazine-HCTZ 100-50 mg capsule0.75USD capsule
HydrALAZINE HCl 50 mg tablet0.67USD tablet
Apresoline 50 mg tablet0.65USD tablet
HydrALAZINE HCl 25 mg tablet0.53USD tablet
HydrALAZINE HCl 10 mg tablet0.47USD tablet
Hydralazine 50 mg tablet0.44USD tablet
Hydralazine 25 mg tablet0.35USD tablet
Apo-Hydralazine 50 mg Tablet0.29USD tablet
Novo-Hylazin 50 mg Tablet0.29USD tablet
Apo-Hydralazine 25 mg Tablet0.24USD tablet
Hydralazine 10 mg tablet0.22USD tablet
Apo-Hydralazine 10 mg Tablet0.11USD tablet
Novo-Hylazin 10 mg Tablet0.11USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6465463No2002-10-152020-09-08Us
US6784177No2004-08-312020-09-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)172-173 °CU.S. Patent 2,484,029.
logP1.00SANGSTER (1993)
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9854
Blood Brain Barrier+0.9487
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.686
P-glycoprotein inhibitor INon-inhibitor0.9478
P-glycoprotein inhibitor IINon-inhibitor0.9826
Renal organic cation transporterNon-inhibitor0.8279
CYP450 2C9 substrateNon-substrate0.8971
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7467
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.526
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5294
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.7719
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.2187 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9253
hERG inhibition (predictor II)Non-inhibitor0.8589
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 phthalazines. These are compounds containing a phthalazine moiety, which consists of a benzene ring fused to a pyridazine, forming a 2,3-benzodiazine skeleton.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Phthalazines
Alternative Parents
Pyridazines and derivatives / Imidolactams / Benzenoids / Heteroaromatic compounds / Amidrazones / Hydrazones / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phthalazine / Imidolactam / Benzenoid / Pyridazine / Heteroaromatic compound / Carboxylic acid amidrazone / Azacycle / Hydrazone / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
hydrazines, phthalazines, azaarene, ortho-fused heteroarene (CHEBI:5775)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tryptamine:oxygen oxidoreductase (deaminating) activity
Specific Function
Cell adhesion protein that participates in lymphocyte extravasation and recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-in...
Gene Name
AOC3
Uniprot ID
Q16853
Uniprot Name
Membrane primary amine oxidase
Molecular Weight
84621.27 Da
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:16116337]
  5. Vidrio H, Medina M: Hypotensive effect of hydroxylamine, an endogenous nitric oxide donor and SSAO inhibitor. J Neural Transm (Vienna). 2007;114(6):863-5. Epub 2007 Mar 26. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:6150080]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Procollagen-proline 4-dioxygenase 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
Uniprot Name
Prolyl 4-hydroxylase subunit alpha-1
Molecular Weight
61048.775 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]
  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. [PubMed: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. [PubMed: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. [PubMed:856725]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 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]
  2. Zhao XJ, Ishizaki T: Metabolic interactions of selected antimalarial and non-antimalarial drugs with the major pathway (3-hydroxylation) of quinine in human liver microsomes. Br J Clin Pharmacol. 1997 Nov;44(5):505-11. [PubMed:9384469]

Drug created on May 16, 2007 14:38 / Updated on November 20, 2018 00:53