Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C8H8N4 |
| Molecular Weight | 160.1759 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NNC1=C2C=CC=CC2=CN=N1
InChI
InChIKey=RPTUSVTUFVMDQK-UHFFFAOYSA-N
InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
DescriptionSources: http://www.drugbank.ca/drugs/DB01275Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/cdi/hydralazine.html
Sources: http://www.drugbank.ca/drugs/DB01275
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/cdi/hydralazine.html
Hydralazine is a direct-acting vasodilator that is used as an antihypertensive agent. 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. Hydralazine is used 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.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9390968
Curator's Comment: some metabolites of hydralazine are known to cross the blood-brain barrier
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL3437 Sources: http://www.drugbank.ca/drugs/DB01275 |
|||
Target ID: GO:0070471 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3354891 |
400.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Hydralazine Hydrochloride Approved UseSevere essential hypertension when the drug cannot be given orally or when there is an urgent need to lower
blood pressure. Launch Date1985 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6653641 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: HYDRALAZINE |
HYDRALAZINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
407 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6653641 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: HYDRALAZINE |
HYDRALAZINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6653641 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: HYDRALAZINE |
HYDRALAZINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
13% |
HYDRALAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
2000 mg single, oral Overdose |
unhealthy, 27 |
Disc. AE: Tachycardia... AEs leading to discontinuation/dose reduction: Tachycardia Sources: |
750 mg single, oral Overdose |
unhealthy, 38 |
Disc. AE: Lethargy, Hypotension... AEs leading to discontinuation/dose reduction: Lethargy Sources: Hypotension Tachycardia Chest pain |
200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy |
Disc. AE: Skin rash, Febrile reaction... AEs leading to discontinuation/dose reduction: Skin rash (rare) Sources: Febrile reaction (rare) |
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Systemic lupus erythematosus synd, Glomerulonephritis... AEs leading to discontinuation/dose reduction: Systemic lupus erythematosus synd Sources: Glomerulonephritis |
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Angina pectoris, Myocardial infarction... AEs leading to discontinuation/dose reduction: Angina pectoris Sources: Myocardial infarction Peripheral neuritis |
40 mg single, intravenous Recommended Dose: 40 mg Route: intravenous Route: single Dose: 40 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Systemic lupus erythematosus synd, Glomerulonephritis... AEs leading to discontinuation/dose reduction: Systemic lupus erythematosus synd Sources: Glomerulonephritis |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Tachycardia | Disc. AE | 2000 mg single, oral Overdose |
unhealthy, 27 |
| Chest pain | Disc. AE | 750 mg single, oral Overdose |
unhealthy, 38 |
| Hypotension | Disc. AE | 750 mg single, oral Overdose |
unhealthy, 38 |
| Lethargy | Disc. AE | 750 mg single, oral Overdose |
unhealthy, 38 |
| Tachycardia | Disc. AE | 750 mg single, oral Overdose |
unhealthy, 38 |
| Febrile reaction | rare Disc. AE |
200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy |
| Skin rash | rare Disc. AE |
200 mg 1 times / day multiple, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy |
| Glomerulonephritis | Disc. AE | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Systemic lupus erythematosus synd | Disc. AE | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Angina pectoris | Disc. AE | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Myocardial infarction | Disc. AE | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Peripheral neuritis | Disc. AE | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
| Glomerulonephritis | Disc. AE | 40 mg single, intravenous Recommended Dose: 40 mg Route: intravenous Route: single Dose: 40 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
| Systemic lupus erythematosus synd | Disc. AE | 40 mg single, intravenous Recommended Dose: 40 mg Route: intravenous Route: single Dose: 40 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [IC50 >1000 uM] | ||||
| no | ||||
| unlikely | ||||
| unlikely | ||||
| unlikely | ||||
| unlikely | ||||
| yes [IC50 197 uM] | ||||
| yes [Ki 83 uM] | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Diesel exhaust induced pulmonary and cardiovascular impairment: the role of hypertension intervention. | 2013-04-15 |
|
| Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity. | 2013-02-25 |
|
| Early treatment with olmesartan prevents juxtamedullary glomerular podocyte injury and the onset of microalbuminuria in type 2 diabetic rats. | 2012-05 |
|
| Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011-07-14 |
|
| Antiatherogenic effect of bisvanillyl-hydralazone, a new hydralazine derivative with antioxidant, carbonyl scavenger, and antiapoptotic properties. | 2011-06 |
|
| Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway. | 2011-05 |
|
| HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats. | 2010-09 |
|
| Hydralazine for essential hypertension. | 2010-08-04 |
|
| Chitosan nanoparticle-based neuronal membrane sealing and neuroprotection following acrolein-induced cell injury. | 2010-01-29 |
|
| D-penicillamine-induced autoimmunity: relationship to macrophage activation. | 2009-09 |
|
| Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis. | 2009-06 |
|
| Administration of angiotensin II, but not catecholamines, induces accumulation of lipids in the rat heart. | 2009-02-14 |
|
| 4-Hydrazino-2-(methyl-sulfan-yl)-pyrimidine. | 2009-01-31 |
|
| Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. | 2009-01-01 |
|
| "Pulse" treatment with high-dose angiotensin blocker reverses renal arteriolar hypertrophy and regresses hypertension. | 2009-01 |
|
| Hydralazine-induced cholestatic hepatitis. | 2008-12-19 |
|
| Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition. | 2008-12 |
|
| The prince and the pauper. A tale of anticancer targeted agents. | 2008-10-23 |
|
| Simultaneous posterior ischemic optic neuropathy, cerebral border zone infarction, and spinal cord infarction after correction of malignant hypertension. | 2008-09 |
|
| Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. | 2008-07 |
|
| Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis. | 2008 |
|
| Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition. | 2007-12 |
|
| D-Penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease. | 2007-11 |
|
| A randomised comparison of hydralazine and mini-bolus diazoxide for hypertensive emergencies in pregnancy: the PIVOT trial. | 2007-08 |
|
| Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial. | 2007-04-03 |
|
| The effects of DNA methylation and histone deacetylase inhibitors on human papillomavirus early gene expression in cervical cancer, an in vitro and clinical study. | 2007-02-26 |
|
| Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II. | 2006-12 |
|
| A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. | 1991-08-01 |
|
| Renal arteriolar diameters in spontaneously hypertensive rats. Vascular cast study. | 1991-07 |
|
| Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism. | 1991-03 |
|
| Cardiotoxicity of hydralazine and minoxidil in the rat. Influence of age. | 1991-02 |
|
| Hemodynamic effects of adenosine agonists in the conscious spontaneously hypertensive rat. | 1990-09 |
|
| Acute cocaine toxicity: antagonism by agents interacting with adrenoceptors. | 1990-06 |
|
| Prevention of arterial disease in experimental renal hypertension. | 1990-04 |
|
| Changes of atrial natriuretic peptide and its messenger RNA with development and regression of cardiac hypertrophy in renovascular hypertensive rats. | 1990-01 |
|
| Myocardial ischemia during isoflurane anesthesia: the effect of substituting halothane. | 1989-06 |
|
| Hydralazine-induced cholestatic jaundice following liver transplantation. | 1989-01 |
|
| Isolated minimal change nephropathy associated with diclofenac. | 1987-07-18 |
|
| Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans. | 1987-05 |
|
| Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs. | 1987-04 |
|
| Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. | 1986-06 |
|
| Drug-associated glomerulopathies. | 1986 |
|
| Comparative study of endralazine and hydralazine for the treatment of hypertension uncontrolled by a beta-blocker and diuretic. | 1986 |
|
| Clinical pharmacology and therapeutic role of prazosin and related alpha-adrenoceptor antagonists. | 1986 |
|
| Therapeutic implications of hypertension-induced glomerular injury. Comparison of enalapril and a combination of hydralazine, reserpine, and hydrochlorothiazide in an experimental model. | 1985-09-27 |
|
| Suppression of ventricular arrhythmias after coronary artery ligation by pinacidil, a vasodilator drug. | 1985-09-01 |
|
| Acute hemodynamic effects of pinacidil and hydralazine in essential hypertension. | 1985-03 |
|
| Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. | 1979-04 |
|
| Immunological side-effects of antihypertensive drugs. | 1979 |
|
| Clinical consequences of polymorphic acetylation of basic drugs. | 1977-09 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/hydralazine.html
Curator's Comment: can also be used intramuscularly or as a rapid intravenous bolus injection directly into the vein. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/040136s005lbl.pdf
Initial dose: 10 mg orally 4 times a day for the first 2 to 4 days. Increase to 25 mg orally 4 times a day for the balance of the first week.
For the second and subsequent weeks, increase dosage to 50 mg orally 4 times a day.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7660828
Hydralazine (0.03-10 mmol.L(-1)) inhibited the activities of both PKA and PKG with IC50 of 1.2 and 2.5 mmol.L(-1), respectively
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| Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
334611
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WHO-ATC |
C02DB02
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WHO-ESSENTIAL MEDICINES LIST |
12.3
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FDA ORPHAN DRUG |
166703
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NDF-RT |
N0000175379
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WHO-VATC |
QC02LG02
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WHO-VATC |
QC02DB02
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LIVERTOX |
NBK548580
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NCI_THESAURUS |
C270
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NDF-RT |
N0000175564
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WHO-ATC |
C02LG02
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86-54-4
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5775
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26NAK24LS8
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5470
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26NAK24LS8
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7326
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126699
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Hydralazine
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3637
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DB01275
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SUB08059MIG
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DTXSID4023129
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CHEMBL276832
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HYDRALAZINE
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100000084193
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1
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201-680-3
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m6072
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C62032
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D006830
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1384
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ACTIVE MOIETY
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
SALT/SOLVATE (PARENT)