Hydralazine

Identification

Summary

Hydralazine is an antihypertensive agent used for the management of essential hypertension or severe hypertension associated with conditions requiring immediate action, heart failure, and pre-eclampsia or eclampsia .

Brand Names
Apresoline, Bidil
Generic Name
Hydralazine
DrugBank Accession Number
DB01275
Background

Originally developed in the 1950s as a malaria treatment, hydralazine showed antihypertensive ability and was soon repurposed.15 Hydralazine is a hydrazine derivative vasodilator used alone or as adjunct therapy in the treatment of hypertension and only as adjunct therapy in the treatment of heart failure.10,18,19 Hydralazine is no longer a first line therapy for these indications since the development of newer antihypertensive medications.16

Hydralazine hydrochloride was FDA approved on 15 January 1953.17

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 160.1759
Monoisotopic: 160.074896276
Chemical Formula
C8H8N4
Synonyms
  • (1Z)-1(2H)-Phthalazinone hydrazone
  • (2H)-Phthalazinone hydrazone
  • 1-Hydrazinophthalazine
  • 1-Phthalazinylhydrazine
  • 6-Hydralazine
  • Hidralazina
  • Hydralazin
  • Hydralazine
  • Hydralazinum
  • Hydrallazine
  • Hydrazinophthalazine
  • Hydrazone 1(2H)-phthalazinone
  • Hypophthalin
  • Idralazina
  • Phthalazin-1-ylhydrazine

Pharmacology

Indication

Hydralazine is indicated alone or adjunct to standard therapy to treat essential hypertension.18 A combination product with isosorbide dinitrate is indicated as an adjunct therapy in the treatment of heart failure.19

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure.18 Hydralazine has a short duration of action of 2-6h.10 This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg.18 Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.18

Mechanism of action

Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure.10,12 The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions.11 This decrease in vascular resistance leads to increased heart rate, stroke volume, and cardiac output.18

Hydralazine also competes with protocollagen prolyl hydroxylase (CPH) for free iron.12 This competition inhibits CPH mediated hydroxylation of HIF-1α, preventing the degradation of HIF-1α.12 Induction of HIF-1α and VEGF promote proliferation of endothelial cells and angiogenesis.12

TargetActionsOrganism
AMembrane primary amine oxidase
inhibitor
Humans
UProlyl 4-hydroxylase subunit alpha-1
inhibitor
Humans
UHypoxia-inducible factor 1-alpha
inducer
Humans
Absorption

Taking oral hydralazine with food improves the bioavailability of the drug.13 An intravenous dose of 0.3mg/kg leads to an AUC of 17.5-29.4µM*min and a 1mg/kg oral dose leads to an AUC of 4.0-30.4µM*min.14 The Cmax of oral hydralazine is 0.12-1.31µM depending on the acetylator status of patients.14

Volume of distribution

The volume of distribution is 1.34±0.79L/kg in congestive heart failure patients and 1.98±0.22L/kg in hypertensive patients.9

Protein binding

Hydralazine is 87% protein bound in serum18 likely to human serum albumin.2

Metabolism

Acetylation is a minor metabolic pathway for hydralazine; the major pathway is hydroxylation followed by glucuronidation.4 There are 5 identified metabolic pathways for hydralazine.1,7,5,4,6,8

Hydralazine can be metabolized to phthalazine or α-ketoglutarate hydrazone.1,4 These metabolites can be further converted to phthalazinone or hydralazine can be metabolized directly to phthalazinone.1,4

Hydralazine can undergo a reversible converstion to the active hydralazine acetone hydrazone.6,8

Hydralazine is spontaneously converted to the active pyruvic acid hydrazone or the pyruvic acid hydrazone tricyclic dehydration product, and these metabolites can convert back and forth between these 2 forms.1,5

Hydralazine can be converted to hydrazinophthalazinone, which is further converted to the active acetylhydrazinophthalazinone.1,4

The final metabolic process hydralazine can undergo is the conversion to an unnamed hydralazine metabolite, which is further metabolized to 3-methyl-s-triazolophthalazine (MTP).1 MTP can be metabolized to 9-hydroxy-methyltriazolophthalazine or 3-hydroxy-methyltriazolophthalazine; the latter is converted to triazolophthalazine.1

Hover over products below to view reaction partners

Route of elimination

<10% of hydralazine is recovered in the feces; 65-90% is recovered in the urine.9

Half-life

Hydralazine has a half life of 2.2-7.8h in rapid acetylators and 2.0-5.8h in slow acetylators.4,18 The half life in heart failure patients is 57-241 minutes with an average of 105 minutes and in hypertensive patients is 200 minutes for rapid acetylators and 297 minutes for slow acetylators.9

Clearance

The majority of hydralazine clearance is extrahepatic- 55% for rapid acetylators and 70% for slow acetylators.9 The average clearance in congestive heart failure patients is 1.77±0.48L/kg/h,9 while hypertensive patients have an average clearance of 42.7±8.9mL/min/kg.14

Adverse Effects
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Toxicity

The oral LD50 in rats is 173-187mg/kg and the highest known dose an adult human has survived is 10g orally.18

Patients experiencing an overdose may present with hypotension, tachycardia, headache, flushing, myocardial ischemia, myocardial infarction, cardiac arrhythmia, and shock.18 Overdose can be treated through emptying the gastric contents and administering activated charcoal, though these treatments may cause further arrhythmias and shock.18 Supportive and symptomatic treatment should be administered.18

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
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Hydralazine.
AcebutololAcebutolol may increase the hypotensive activities of Hydralazine.
AceclofenacAceclofenac may decrease the antihypertensive activities of Hydralazine.
AcemetacinAcemetacin may decrease the antihypertensive activities of Hydralazine.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Hydralazine.
AcetaminophenAcetaminophen may decrease the excretion rate of Hydralazine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Hydralazine which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the antihypertensive activities of Hydralazine.
Interactions
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Food Interactions
  • Take with or without food. Food increases exposure to hydralazine, though this may not be clinically significant.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Hydralazine hydrochlorideFD171B778Y304-20-1ZUXNZUWOTSUBMN-UHFFFAOYSA-N
Product Images
International/Other Brands
Alphapress (Alphapharm) / Aprezin (Johnson) / Cesoline W (Pharmasant) / Cesoline Y (Pharmasant) / Diazide (The Central) / Hidral (Biocontrol) / Pressfall (Nisshin Seiyaku) / Serpathiazide (Washington)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ApresolineSolution20 mg / mLIntravenousSterimax Inc1992-12-31Not applicableCanada flag
Apresoline hydrochlorideTablet, coated50 mg/1OralNovartis Pharmaceuticals Corporation1953-01-152010-10-07US flag
Apresoline hydrochlorideTablet, coated25 mg/1OralNovartis Pharmaceuticals Corporation1953-01-152010-10-07US flag
Apresoline hydrochlorideTablet, coated50 mg/1OralPhysicians Total Care, Inc.1995-02-172010-10-07US flag
Apresoline hydrochlorideTablet, coated10 mg/1OralNovartis Pharmaceuticals Corporation1953-01-152010-10-07US flag
Apresoline hydrochlorideTablet, coated100 mg/1OralNovartis Pharmaceuticals Corporation1953-01-152010-10-07US flag
Apresoline Tablets, 10mgTablet10 mgOralSterimax Inc1952-12-312005-07-22Canada flag
Apresoline Tablets, 25mgTablet25 mgOralSterimax Inc1952-12-312005-07-19Canada flag
Apresoline Tablets, 50mgTablet50 mgOralSterimax Inc1952-12-312005-07-19Canada flag
Asn-hydralazineTablet50 mgOralAscend Laboratories LtdNot applicableNot applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-hydralazineTablet10 mgOralApotex Corporation1990-12-31Not applicableCanada flag
Apo-hydralazineTablet50 mgOralApotex Corporation1991-12-31Not applicableCanada flag
Apo-hydralazineTablet25 mgOralApotex Corporation1991-12-31Not applicableCanada flag
HydralazineTablet100 mg/1OralNivagen Pharmaceuticals, Inc.2017-02-15Not applicableUS flag
HydralazineTablet50 mg/1OralNivagen Pharmaceuticals, Inc.2017-02-15Not applicableUS flag
HydralazineTablet25 mg/1OralREMEDYREPACK INC.2018-10-242020-05-27US flag
HydralazineTablet50 mg/1OralCardinal Health2009-09-142020-10-31US flag
HydralazineTablet25 mg/1OralNivagen Pharmaceuticals, Inc.2017-02-15Not applicableUS flag
HydralazineTablet25 mg/1OralCardinal Health2009-09-142020-11-30US flag
Hydralazine HClTablet, film coated50 mg/1OralDirectrx2019-04-30Not applicableUS flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ไดลาซิน 25Tablet, coated25 mgOralบริษัท พอนด์ เคมีคอล จำกัด2017-10-21Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BiDilHydralazine hydrochloride (37.5 mg/1) + Isosorbide dinitrate (20 mg/1)Tablet, film coatedOralArbor Pharmaceuticals, Inc.2012-12-05Not applicableUS flag24338 01020180907 15195 ecm0g8
BiDilHydralazine hydrochloride (37.5 mg/1) + Isosorbide dinitrate (20 mg/1)Tablet, film coatedOralRemedy Repack2013-10-082013-10-09US flag
BiDilHydralazine hydrochloride (37.5 mg/1) + Isosorbide dinitrate (20 mg/1)Tablet, film coatedOralArbor Pharmaceuticals2005-06-232015-12-31US flag12948 0001 12 nlmimage10 2f131798
Hydralazine HCl and HydrochlorothiazideHydralazine hydrochloride (50 mg/1) + Hydrochlorothiazide (50 mg/1)CapsuleOralPar Pharmaceutical1985-10-212009-10-29US flag
Hydralazine HCl and HydrochlorothiazideHydralazine hydrochloride (25 mg/1) + Hydrochlorothiazide (25 mg/1)CapsuleOralPar Pharmaceutical1985-10-212009-10-29US flag
Hydralazine HCl and HydrochlorothiazideHydralazine hydrochloride (100 mg/1) + Hydrochlorothiazide (50 mg/1)CapsuleOralPar Pharmaceutical1985-10-212009-10-29US flag
Ser-Ap-EsHydralazine hydrochloride (25 mg/1) + Hydrochlorothiazide (15 mg/1) + Reserpine (0.1 mg/1)Tablet, coatedOralNovartis Pharmaceuticals Corporation1960-02-112019-09-10US flag
Ser-AP-ES TabHydralazine hydrochloride (25 mg) + Hydrochlorothiazide (15 mg) + Reserpine (0.1 mg)TabletOralNovartis1960-12-312000-08-02Canada flag
มาโน-เอป-เอสHydralazine (25 MG) + Hydrochlorothiazide (15 MG) + Reserpine (0.1 MG)TabletOralบริษัท โรงงานเภสัชกรรมแหลมทองการแพทย์ จำกัด จำกัด1987-08-13Not applicableThailand flag
วี-พี-ซีนHydralazine (25 MG) + Hydrochlorothiazide (15 MG) + Reserpine (0.1 MG)TabletOralบริษัท วี แอนด์ พี ลาบอราตอรี่ จำกัด จำกัด1988-04-032020-09-14Thailand flag

Categories

ATC Codes
C02DB02 — HydralazineC02LG02 — Hydralazine and diuretics
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboxylic acid amidrazone / Heteroaromatic compound / Hydrazone / Hydrocarbon derivative / Imidolactam / Organic nitrogen compound / Organonitrogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
hydrazines, phthalazines, azaarene, ortho-fused heteroarene (CHEBI:5775)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
26NAK24LS8
CAS number
86-54-4
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

References

Synthesis Reference

U.S. Patent 2,484,029.

General References
  1. Hofstra AH: Metabolism of hydralazine: relevance to drug-induced lupus. Drug Metab Rev. 1994;26(3):485-505. doi: 10.3109/03602539408998315. [Article]
  2. Bolattin M, Nandibewoor S, Joshi S, Dixit S, Chimatadar S: Interaction of Hydralazine with Human Serum Albumin and Effect of β-Cyclodextrin on Binding: Insights from Spectroscopic and Molecular Docking Techniques Industrial & Engineering Chemistry Research. 2016 Apr 24;55(19):5454-5464. [Article]
  3. Machado JD, Gomez JF, Betancor G, Camacho M, Brioso MA, Borges R: Hydralazine reduces the quantal size of secretory events by displacement of catecholamines from adrenomedullary chromaffin secretory vesicles. Circ Res. 2002 Nov 1;91(9):830-6. doi: 10.1161/01.res.0000039530.30495.6f. [Article]
  4. Reidenberg MM, Drayer D, DeMarco AL, Bello CT: Hydralazine elimination in man. Clin Pharmacol Ther. 1973 Nov-Dec;14(6):970-7. doi: 10.1002/cpt1973146970. [Article]
  5. Haegele KD, Skrdlant HB, Talseth T, McNay JL, Shepherd AM, Clementi WA: Quantitative analysis of hydralazine pyruvic acid hydrazone, the major plasma metabolite of hydralazine. J Chromatogr. 1980 Jan 4;187(1):171-9. doi: 10.1016/s0021-9673(00)87883-8. [Article]
  6. Talseth T, McNay JL, Haegele KD: Hypotensive effect of the hydralazine--acetone hydrazone in conscious rabbits: evidence for its back-conversion to hydralazine in vivo. J Cardiovasc Pharmacol. 1982 May-Jun;4(3):370-4. doi: 10.1097/00005344-198205000-00005. [Article]
  7. Reece PA: Hydralazine and related compounds: chemistry, metabolism, and mode of action. Med Res Rev. 1981 Spring;1(1):73-96. [Article]
  8. Iwaki M, Ogiso T, Ito Y: Pharmacokinetics and biotransformation of hydralazine acetone hydrazone, a metabolite of hydralazine, in the rat. J Pharm Sci. 1989 Oct;78(10):867-73. doi: 10.1002/jps.2600781018. [Article]
  9. Mulrow JP, Crawford MH: Clinical pharmacokinetics and therapeutic use of hydralazine in congestive heart failure. Clin Pharmacokinet. 1989 Feb;16(2):86-9. doi: 10.2165/00003088-198916020-00003. [Article]
  10. Herman LL, Tivakaran VS: Hydralazine . [Article]
  11. Jacobs M: Mechanism of action of hydralazine on vascular smooth muscle. Biochem Pharmacol. 1984 Sep 15;33(18):2915-9. doi: 10.1016/0006-2952(84)90216-8. [Article]
  12. 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. [Article]
  13. Walden RJ, Hernandez R, Witts D, Graham BR, Prichard BN: Effect of food on the absorption of hydralazine in man. Eur J Clin Pharmacol. 1981;20(1):53-8. doi: 10.1007/bf00554667. [Article]
  14. Ludden TM, McNay JL Jr, Shepherd AM, Lin MS: Variability of plasma hydralazine concentrations in male hypertensive patients. Arthritis Rheum. 1981 Aug;24(8):987-93. doi: 10.1002/art.1780240802. [Article]
  15. Aeddula NR, Pathireddy S, Ansari A, Juran PJ: Hydralazine-associated antineutrophil cytoplasmic antibody vasculitis with pulmonary-renal syndrome. BMJ Case Rep. 2018 Nov 8;2018. pii: bcr-2018-227161. doi: 10.1136/bcr-2018-227161. [Article]
  16. McInnes G (2007). 84. In Comprehensive Hypertension (pp. 1037-1048). Elsevier. [ISBN:978-0-323-03961-1]
  17. FDA Approved Drug Products: Apresoline Hydralazine Hydrochloride Tablets and Injections (Discontinued) [Link]
  18. FDA Approved Drug Products: Hydralazine Hydrochloride Oral Tablets [Link]
  19. FDA Approved Drug Products: Hydralazine and Isosorbide Dinitrate Oral Tablets [Link]
Human Metabolome Database
HMDB0015400
KEGG Drug
D08044
KEGG Compound
C07040
PubChem Compound
3637
PubChem Substance
46507533
ChemSpider
3511
BindingDB
81461
RxNav
5470
ChEBI
5775
ChEMBL
CHEMBL276832
ZINC
ZINC000012360535
Therapeutic Targets Database
DAP000728
PharmGKB
PA449894
PDBe Ligand
HLZ
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Hydralazine
AHFS Codes
  • 24:08.20 — Direct Vasodilators
PDB Entries
3ltw
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedPreventionChronic Hemodialysis (ESRD)1
4CompletedTreatmentCongestive Heart Failure (CHF)1
4CompletedTreatmentHigh Blood Pressure (Hypertension)2
4CompletedTreatmentStage II Hypertension1
4RecruitingDiagnosticMitral Valve Insufficiency / Systolic Heart Failure Stage D (Disorder)1
4RecruitingTreatmentDiabetes / Heart Failure1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedTreatmentPregnancy Induced Hypertension (PIH)1
3Not Yet RecruitingTreatmentAlzheimer's Disease (AD)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 / mL
Powder20 mg/1ampoule
Tablet, coatedOral10 mg/1
Tablet, coatedOral100 mg/1
Tablet, coatedOral25 mg/1
Tablet, coatedOral50 mg/1
Tablet, film coatedOral
CapsuleOral
InjectionIntramuscular; Intravascular20 mg/1mL
InjectionIntramuscular; Intravenous20 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
InjectionIntramuscular; Intravenous
TabletOral10 mg
TabletOral25 mg
TabletOral50 mg
Tablet, coatedOral
Tablet, coatedOral50 mg
TabletOral
Tablet, coatedOral10 mg
Tablet, coatedOral25 mg
Tablet, sugar coatedOral25 mg
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)Region
US6465463No2002-10-152020-09-08US flag
US6784177No2004-08-312020-09-08US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)172-173 °CU.S. Patent 2,484,029.
boiling point (°C)251.3ChemSpider
water solubility<1mg/mLChemSpider
logP1.00SANGSTER (1993)
pKa7.3Machado (2002)
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

Targets

Drugtargets
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Ubiquitin protein ligase binding
Specific Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transp...
Gene Name
HIF1A
Uniprot ID
Q16665
Uniprot Name
Hypoxia-inducible factor 1-alpha
Molecular Weight
92669.595 Da
References
  1. 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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
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. 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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bolattin M, Nandibewoor S, Joshi S, Dixit S, Chimatadar S: Interaction of Hydralazine with Human Serum Albumin and Effect of β-Cyclodextrin on Binding: Insights from Spectroscopic and Molecular Docking Techniques Industrial & Engineering Chemistry Research. 2016 Apr 24;55(19):5454-5464. [Article]

Drug created on May 16, 2007 20:38 / Updated on June 23, 2021 06:08