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Last update 16 May 2025

Hydralazine Hydrochloride

Last update 16 May 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryHydralazine Hydrochloride, marketed under the trade name Dralzine®, is an antihypertensive medication that has been approved since 1952 for the treatment of hypertension. Developed by Novartis, Hydralazine Hydrochloride works as AOC3 inhibitors, aiding in the management of essential hypertension, severe hypertension, heart failure, pre-eclampsia, and eclampsia. Its mechanism of action has made it a reliable option for individuals requiring immediate action for hypertension. As a trusted medication in the field of hypertension treatment, Hydralazine Hydrochloride has helped countless individuals manage their blood pressure and maintain healthy lifestyles.

Drug Type

Small molecule drug

Synonyms

(1Z)-1(2H)-Phthalazinone hydrazone, (2H)-Phthalazinone hydrazone, 1-Hydrazinophthalazine

+ [17]

Target-

Action-

Mechanism-

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesUrogenital Diseases

Active Indication

Heart FailureEclampsiaHypertensive Encephalopathy+ [1]

Inactive Indication

Dystrophy, Macular

Originator Organization

Novartis Pharma AG

Active Organization

Sun Pharma Japan Ltd.

Shanghai ZhongXi Pharmaceutical Co. Ltd.

Novartis Pharma AG

Inactive Organization

Novartis Pharmaceuticals Corp.

MacuCLEAR, Inc.

License Organization-

Drug Highest PhaseApproved

First Approval Date

(01 Jan 1952),

Hypertension

RegulationOrphan Drug (United States)

Structure/Sequence

Molecular FormulaC8H9ClN4

InChIKeyZUXNZUWOTSUBMN-UHFFFAOYSA-N

CAS Registry304-20-1

Clinical Trials associated with Hydralazine Hydrochloride

NCT06360601

/ RecruitingPhase 1/2IIT

The Effect of Intravenous Infusion of Labetalol Versus Hydralazine on Cerebral Hemodynamics of Preeclampsia Patients Prospective Randamized Study

We study the effect of intravenous labetalol versus hydralazine in sever preeclampsia patients on cerebral blood flow and neurological outcome

Start Date01 Apr 2024

Sponsor / Collaborator

Tanta University

NCT04842552

/ Unknown statusPhase 3IIT

The Effect of Hydralazine on the Early Stage of Alzheimer's Disease: A Randomized Clinical Trial

It has been recently discovered that the FDA-approved drug, hydralazine, has anti-neurodegenerative efficacy based on three intriguing observations. hydralazine; 1) activates the Nrf2 pathway that controls more than 200 antioxidant proteins, 2) rejuvenates mitochondria and increases their respiration capacity and adenosine triphosphate production, 3) activates autophagy which has pathophysiological roles such as intracellular aggregate clearance. There is an emerging agreement that autophagy-lysosome defects occur early in the pathogenesis of Alzheimer's disease (AD). Nrf2 is another pathway known to be impaired in the hippocampus of AD patients who need antioxidant protection the most. Rejuvenation of mitochondria is crucial for fighting AD, as neuronal cells need more energy to afford activation of pathways such as autophagy and Nrf2. The prime objective of this application is to conduct a randomized clinical trial to assess the efficacy of hydralazine in early-stage AD patients who take one of the acetylcholinesterase inhibitor (AChEI) donepezil, rivastigmine, or galantamine.

Start Date02 Aug 2021

Sponsor / Collaborator

Shahid Sadoughi University of Medical Sciences and Health Services

[+1]

NCT06218199

/ RecruitingPhase 4

Diuretics vs. Afterload Reduction for Treatment of HeartLogic Alerts (DART-HA)

The DART-HA study is a single-center, open label, trial intended to evaluate the clinical efficacy of standard treatment options for congestive heart failure (observation, diuretic or afterload reduction therapy) in patients without new symptoms who have developed abnormalities of the HeartLogic heart failure diagnostic feature.

Start Date08 Jul 2021

Sponsor / Collaborator

Boston Scientific Corp.

100 Clinical Results associated with Hydralazine Hydrochloride

100 Translational Medicine associated with Hydralazine Hydrochloride

100 Patents (Medical) associated with Hydralazine Hydrochloride

6,863

Literatures (Medical) associated with Hydralazine Hydrochloride

01 Jul 2025·JOURNAL OF MOLECULAR STRUCTURE

Phthalazine ring incorporated 3-methyl-2,6-diarylpiperidin-4-one based hybrids: Synthesis, Spectral characterization, DFT studies, Molecular docking, In silico ADME predictions and Antibacterial activity

Author: Dar, Tanzeer Ahmad ; Thirunavukkarasu, Balasankar ; Uthrapathy, Surya ; Karunanithi, Udhayanithi Muthusamy

Phthalazine ring bearing piperidin-4-one based hydrazone derivatives were synthesized by incorporating a biol. active phthalazine ring into the piperidin-4-one moeity through hydrazone formation.The structure of the compounds were identified by FT-IR, ¹H NMR, ¹³C NMR, HSQC and HRMS-ESI spectral studies which furnished the clear evidence of the expected structures.From the NMR anal., it was evident that the piperidin-4-one ring possesses a chair conformation, and all the compounds display an (E)-configuration around the C=N bond.DFT calculations for 4-chlorophenyl substituted derivative, using a 6-311++G(d,p) basis set, provided insights into the electronic properties of the compoundsHydrazone ligands were docked with the bacterial protein (PDB ID: 4HLC) through Autodock 4.0.All the ligands demonstrate significant binding energy values between -6.15 and -7.79 kcal/mol.ADME studies reveals the favorable pharmacokinetic profiles of the compoundsThe antibacterial activity of the synthesized compounds was evaluated using the agar well diffusion method, where the inhibitory zone was measured to assess their antibacterial properties.Compounds with bromo and Me substitutions show outstanding inhibition against the pathogens used.

01 May 2025·JOURNAL OF MOLECULAR LIQUIDS

Physicochemical and spectral investigation of interactions between hydralazine hydrochloride and dextrose in aqueous solutions

Author: Kumar, Parveen ; Ahir, Palak ; Thakur, Vishal ; Sharma, Sunaina ; Kumar, Sunil

Hydralazine hydrochloride (HHC) is an antihypertensive drug prescribed to hypertension patients during heart failure and pregnancy.In this work, we have introduced a novel approach to understand the mol. basis of HHC-dextrose interactions, paving the way for tailored therapeutic strategies in hypertension management.For this purpose, the physicochem. properties of HHC (m/mol.kg-₁ = _0.001-0.010) in water and 5% w/v dextrose solution (D5W) have been studied by measuring densities (ρ), sound velocities (u), molar conductance (Λm) and viscosities (η) for HHC at four temperatures (T/K =_{300.15-315.15}) under atm. pressure (P/kPa = _101.325).The exptl. measured data were then used to calculate apparent molar parameters (ΦV,ΦK), partial molar parameters (Φ0V,Φ0K) and transfer parameters (ΔtrΦ0V,ΔtrΦ0K,ΔtrB).At 300.15 K, on transposing to D5W solvent from water, Φ0V decreased from 144.05 to 117.21, Φ0K decreased from -15.89 to -18.73 and B-coefficient decreased from 5.62 to 5.60, generating neg. transfer parameters.A similar trend prevailed at other temperatures also and the neg. values of transfer parameters advocate the dominance of ion-hydrophobic, hydrophobic-hydrophobic and hydrophilic-hydrophobic interactions in the solutionsMoreover, the structure-making behavior of HHC in water and D₅W was confirmed by pos. values of Hepler' s constant (and2Φ0V/andT₂)P and Walden product (((d(Λ0mη0))/dT))P as well as from the neg. values of dB/dT.Furthermore, hyperchromic shift in UV-visible spectra, decrease in fluorescence intensity, and disarticulation in FTIR spectra (recorded at T = 298.15 K and P = 101.325 kPa) strengthen the physicochem. outcomes.Comprehending these interactions is crucial for developing optimized formulations that enhance drug delivery, drug absorption and ultimately improve blood pressure control and patient outcomes.Further, these findings could also be helpful in determining various pharmacodynamic and pharmacokinetic parameters like therapeutic efficacy, stability, solubility and bioavailability of drug HHC.

15 Apr 2025·JOURNAL OF CLINICAL INVESTIGATION

Sequential carbonyl derivatives and hydrazone adduct formation on myeloperoxidase contribute to development of ANCA vasculitis

Article

Author: Mclnnis, Elizabeth A ; Hu, Peiqi ; Falk, Ronald J ; Jennette, J Charles ; Orzechowski, Nicole M ; Poulton, John S ; Zeitler, Evan M ; Derebail, Vimal K ; Chen, Dhruti P ; Xi, Gang ; Wu, Eveline Y ; Free, Meghan E ; Lardinois, Olivier

Drug-induced autoimmune diseases are increasingly recognized, although mechanistic insight into disease causation is lacking. Hydralazine exposure has been linked to autoimmune diseases, including antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. Our hypothesis posits that hydralazine covalently binds to myeloperoxidase (MPO), triggering the autoimmune response in ANCA vasculitis. In vitro, we observed formation of carbonyl derivatives on amine groups in the presence of acrolein. This facilitated the subsequent binding of hydralazine to heme-containing proteins, including MPO, via a Michael addition. Our studies demonstrated that carbonyl derivatives and hydrazone adducts induced conformational changes in the MPO heavy chain, potentially changing its immunogenicity. We identified hydrazone adducts on circulating MPO in patients with hydralazine-associated ANCA vasculitis. These patients exhibited elevated anti-MPO IgM levels, while anti-MPO IgG levels were comparable between hydralazine-associated and nonhydralazine-associated vasculitis patients. IgM isolated from patients with hydralazine-associated MPO ANCA demonstrated a heightened affinity to hydralazine-modified MPO and activated neutrophil-like HL-60 cells. Hydralazine-modified MPO was pathogenic, as demonstrated by splenocyte transfer in a mouse model of ANCA vasculitis. Our findings unveil a mechanism of drug-induced autoimmunity wherein stepwise chemical modifications of MPO lead to conformational changes and hydrazone adduct formation, producing a neoantigen that generates pathogenic autoantibodies.

News (Medical) associated with Hydralazine Hydrochloride

13 Sep 2024

·www.biospace.com

Rising Pharmaceuticals announces commercial availability of Edetate calcium disodium injection in the United States

Rising’s Edetate calcium disodium injection is FDA-approved and immediately available Edetate calcium disodium injection is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults. 1 EAST BRUNSWICK, N.J.--(BUSINESS WIRE)-- #adultleadpoisoning --Rising Pharma Holdings, Inc., d/b/a Rising Pharmaceuticals, Inc. (“Rising”) announced commercial availability of Edetate calcium disodium injection. Access to Rising’s product continues despite a commercial shortage of this product in the United States. Rising’s Edetate calcium disodium injection is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults. “Rising’s Edetate calcium disodium injection provides an available option for health care providers to treat patients exposed to lead poisoning,” said David Picard, Executive Vice President for Institutional Markets at Rising. “This continued availability reflects our ongoing commitment to addressing product supply shortages to help ensure health care providers have access to products for patient care.” Edetate Calcium Disodium injection, USP 5 mL single-dose vial containing 200 mg of edetate calcium disodium per mL (1000 mg per vial) Supplied in boxes containing 5 vials (NDC 64980-588-51) Wholesale Item Numbers Cardinal 5855416 Cencora 10291753 Mckesson 2830826 Morris Dickson 296285 ___________________________ 1 Full prescribing information and label available at and provided below. About Rising Pharmaceuticals, Inc. Rising Pharmaceuticals, Inc. is a leading provider of generic and specialty-branded pharmaceuticals in the U.S. Rising focuses on the development, regulatory, and commercial aspects of the product life cycle while outsourcing manufacturing to its network of strategic CMO and CDO partners. With over 182 commercialized generic medicines and over 620 active SKUs, Rising has one of the largest portfolios of any generic pharmaceutical company in the US market. Through an extensive global network of manufacturing facilities, Rising supplies almost 9 billion doses of generic medicine to the market annually. The Company is based in New Brunswick, New Jersey. For more information about the Company, please visit . Edetate Calcium Disodium Injection, USP Intravenous or Intramuscular Use Rx Only WARNINGS Edetate calcium disodium injection is capable of producing toxic effects which can be fatal. Lead encephalopathy is relatively rare in adults, but occurs more often in pediatric patients in whom it may be incipient and thus overlooked. The mortality rate in pediatric patients has been high. Patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following intravenous infusion; the intramuscular route is preferred for these patients. In cases where the intravenous route is necessary, avoid rapid infusion. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded. DESCRIPTION Edetate Calcium Disodium injection, USP is a sterile, injectable, chelating agent in concentrated solution for intravenous infusion or intramuscular injection. Each 5 mL single-dose vial contains 1000 mg of edetate calcium disodium (equivalent to 200 mg/mL) in water for injection and sodium hydroxide (as pH adjuster). Chemically, this product is called [[N,N'-1,2-ethanediyl-bis[N-(carboxymethyl)-glycinato]](4-)-N,N’,O,O’,ON,ON’]-, disodium, hydrate, (OC-6-21)-Calciate(2-). CLINICAL PHARMACOLOGY The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron mobilized are not significant. Copper1 is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased.1 Edetate calcium disodium is poorly absorbed from the gastrointestinal tract. In blood, all the drug is found in the plasma. Edetate calcium disodium does not appear to penetrate cells; it is distributed primarily in the extracellular fluid with only about 5% of the plasma concentration found in spinal fluid. The half life of edetate calcium disodium is 20 to 60 minutes. It is excreted primarily by the kidney, with about 50% excreted in one hour and over 95% within 24 hours.2 Almost none of the compound is metabolized. The primary source of lead chelated by edetate calcium disodium is from bone; subsequently, soft-tissue lead is redistributed to bone when chelation is stopped.3,4 There is also some reduction in kidney lead levels following chelation therapy. It has been shown in animals that following a single dose of edetate calcium disodium urinary lead output increases, blood lead concentration decreases, but brain lead is significantly increased due to internal redistribution of lead.5 (See WARNINGS .) These data are in agreement with the recent results of others in experimental animals showing that after a five day course of treatment there is no net reduction in brain lead.6 INDICATIONS AND USAGE Edetate calcium disodium injection is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults. Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead. CONTRAINDICATIONS Edetate calcium disodium injection should not be given during periods of anuria, nor to patients with active renal disease or hepatitis. WARNINGS See boxed warning . PRECAUTIONS General Precautions Edetate calcium disodium may produce the same renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Treatment-induced nephrotoxicity is dose-dependent and may be reduced by assuring adequate diuresis before therapy begins. Urine flow must be monitored throughout therapy which must be stopped if anuria or severe oliguria develop. The proximal tubule hydropic degeneration usually recovers upon cessation of therapy. Edetate calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease. Patients should be monitored for cardiac rhythm irregularities and other ECG changes during intravenous therapy. Information for patients Patients should be instructed to immediately inform their physician if urine output stops for a period of 12 hours. Laboratory tests Urinalysis and urine sediment, renal and hepatic function and serum electrolyte levels should be checked before each course of therapy and then be monitored daily during therapy in severe cases, and in less serious cases after the second and fifth day of therapy. Therapy must be discontinued at the first sign of renal toxicity. The presence of large renal epithelial cells or increasing number of red blood cells in urinary sediment or greater proteinuria call for immediate stopping of edetate calcium disodium administration. Alkaline phosphatase values are frequently depressed (possibly due to decreased serum zinc levels), but return to normal within 48 hours after cessation of therapy. Elevated erythrocyte protoporphyrin levels (> 35 mcg/dl of whole blood) indicate the need to perform a venous blood lead determination. If the whole blood lead concentration is between 25 to 55 mcg/dl a mobilization test can be considered.7,8 (See Diagnostic Test .) An elevation of urinary coproporphyrin (adults: > 250 mcg/day; pediatric patients under 80 lbs: > 75 mcg/day) and elevation of urinary delta aminolevulinic acid (ALA) (adults: > 4 mg/day; pediatric patients: > 3 mg/m2/day) are associated with blood lead levels > 40 mcg/dl. Urinary coproporphyrin may be falsely negative in terminal patients and in severely iron-depleted pediatric patients who are not regenerating heme.9 In growing pediatric patients long bone x-rays showing lead lines and abdominal x-rays showing radio-opaque material in the abdomen may be of help in estimating the level of exposure to lead. Drug Interactions There is no known drug interference with standard clinical laboratory tests. Steroids enhance the renal toxicity of edetate calcium disodium in animals.7 Edetate calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc.7 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term animal studies have not been conducted with edetate calcium disodium to evaluate its carcinogenic potential, mutagenic potential or its effect on fertility. Pregnancy Category B One reproduction study was performed in rats at doses up to 13 times the human dose and revealed no evidence of impaired fertility or harm to the fetus due to edetate calcium disodium.10 Another reproduction study performed in rats at doses up to about 25 to 40 times the human dose revealed evidence of fetal malformations due to edetate calcium disodium, which were prevented by simultaneous supplementation of dietary zinc.11 There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Labor and Delivery Edetate calcium disodium has no recognized use during labor and delivery, and its effects during these processes are unknown. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when edetate calcium disodium is administered to a nursing woman. Pediatric Use Since lead poisoning occurs in pediatric populations and adults but is frequently more severe in pediatric patients, edetate calcium disodium is used in patients of all ages. The intramuscular route is preferred by some for young pediatric patients. In cases where the intravenous route is necessary, avoid rapid infusion. (See WARNINGS .) Urine flow must be monitored throughout therapy; Edetate Calcium Disodium therapy must be stopped if anuria or severe oliguria develops. (See General Precautions .) At no time should the recommended daily dosage be exceeded. (See DOSAGE AND ADMINISTRATION .) ADVERSE REACTIONS The following adverse effects have been associated with the use of edetate calcium disodium: Body as a Whole: pain at intramuscular injection site, fever, chills, malaise, fatigue, myalgia, arthralgia. Cardiovascular: hypotension, cardiac rhythm irregularities. Renal: acute necrosis of proximal tubules (which may result in fatal nephrosis), infrequent changes in distal tubules and glomeruli. Urinary: glycosuria, proteinuria, microscopic hematuria and large epithelial cells in urinary sediment. Nervous System: tremors, headache, numbness, tingling. Gastrointestinal: cheilosis, nausea, vomiting, anorexia, excessive thirst. Hepatic: mild increases in SGOT and SGPT are common, and return to normal within 48 hours after cessation of therapy. Immunogenic: histamine-like reactions (sneezing, nasal congestion, lacrimation), rash. Hematopoietic: transient bone marrow depression, anemia. Metabolic: zinc deficiency, hypercalcemia. To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or . OVERDOSAGE Symptoms Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dl did not cause any ill effects. Edetate calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning. Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of edetate calcium disodium may produce a more severe zinc deficiency. Treatment Cerebral edema should be treated with repeated doses of mannitol. Steroids enhance the renal toxicity of edetate calcium disodium in animals and, therefore, are no longer recommended.7 Zinc levels must be monitored. Good urinary output must be maintained because diuresis will enhance drug elimination. It is not known if edetate calcium disodium is dialyzable. DOSAGE AND ADMINISTRATION When a source for the lead intoxication has been identified, the patient should be removed from the source, if possible. The recommended dose of edetate calcium disodium for asymptomatic adults and pediatric patients whose blood lead level is 20 mcg/dl (World Health Organization recommended upper allowable level) is 1000 mg/m2/day whether given intravenously or intramuscularly. (See Surface Area Nomogram.) For adults with lead nephropathy, the following dosing regimen has been suggested: 500 mg/m2 every 24 hours for 5 days for patients with serum creatinine levels of 2 to 3 mg/dl, every 48 hours for 3 doses for patients with creatinine levels of 3 to 4 mg/dl, and once weekly for patients with creatinine levels above 4 mg/dl. These regimens may be repeated at one month intervals.12 Edetate calcium disodium, used alone, may aggravate symptoms in patients with very high blood lead levels. When the blood lead level is > 70 mcg/dl or clinical symptoms consistent with lead poisoning are present, it is recommended that edetate calcium disodium be used in conjunction with BAL (dimercaprol). Please consult published protocols and specialized references for dosage recommendations of combination therapy.14-18 Therapy of lead poisoning in adults and pediatric patients with edetate calcium disodium is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on severity of the lead toxicity and the patient’s tolerance of the drug. Edetate calcium disodium is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy and this route is preferred by some for young pediatric patients. Acutely ill individuals may be dehydrated from vomiting. Since edetate calcium disodium is excreted almost exclusively in the urine, it is very important to establish urine flow with intravenous fluid administration before the first dose of the chelating agent is given; however, excessive fluid must be avoided in patients with encephalopathy. Once urine flow is established, further intravenous fluid is restricted to basal water and electrolyte requirements. Administration of edetate calcium disodium should be stopped whenever there is cessation of urine flow in order to avoid unduly high tissue levels of the drug. Edetate calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease. Intravenous Administration Add the total daily dose of edetate calcium disodium (1000 mg/m2/day) to 250-500 mL of 5% dextrose or 0.9% sodium chloride injection. The total daily dose should be infused over a period of 8 to 12 hours. Discard unused portion. Edetate calcium disodium injection is incompatible with 10% dextrose, 10% invert sugar in 0.9% sodium chloride, lactate Ringer’s, Ringer’s, one-sixth molar sodium lactate injections, and with injectable amphotericin B and hydralazine hydrochloride. Intramuscular Administration The total daily dosage (1000 mg/m2/day) should be divided into equal doses spaced 8 to 12 hours apart. Discard unused portion. Lidocaine or procaine should be added to the edetate calcium disodium injection to minimize pain at the injection site. The final lidocaine or procaine concentration of 5 mg/mL (0.5%) can be obtained as follows: 0.25 mL of 10% lidocaine solution per 5 mL concentrated edetate calcium disodium; 1 mL of 1% lidocaine or procaine solution per mL of concentrated edetate calcium disodium. When used alone, regardless of method of administration, edetate calcium disodium should not be given at doses larger than those recommended. Diagnostic Test Several methods have been described for lead mobilization tests using edetate calcium disodium to assess body stores.7, 9,12,13,18 These procedures have advantages and disadvantages that should be reviewed in current references. Edetate calcium disodium mobilization tests should not be performed in symptomatic patients and in patients with blood lead levels above 55 mcg/dl for whom appropriate therapy is indicated. Parenteral drugs should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. HOW SUPPLIED Edetate Calcium Disodium injection, USP 5 mL single-dose vial (NDC 64980-588-05 ) containing 200 mg of edetate calcium disodium per mL (1000 mg per vial), in boxes containing 5 vials (NDC 64980-588-51 ). Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Rx Only This product is non-returnable. REFERENCES 1. Thomas DJ, Chisolm JJ. Lead, zinc and copper decorporation during calcium disodium ethylene diamine tetraacetate treatment of lead-poisoned children. J Pharmacol Exp Therapeu 1986; 239: 829–835. 2. The Pharmacological Basis of Therapeutics, 7th edition, Goodman and Gilman, editors. MacMillan Publishing Company, New York, 1985, pp. 1619–1622. 3. Hammond PB, Aronson AL, Olson WC. The mechanism of mobilization of lead by ethylenediaminetetraacetate. J Pharmacol Exp Therapeu 1967; 157: 196–206. 4. Van deVyver FL, D’Haese PC, Visser WJ, et al. Bone lead in dialysis patients. Kidney Intl 1988; 33: 601–607. 5. Cory-Slecta DA, Weiss B, Cox C. Mobilization and redistribution of lead over the course of calcium disodium ethylene diamine tetraacetate chelation therapy. J Pharmacol Exp Therapeu 1987; 243: 804–813. 6. Chisolm JJ. Mobilization of lead by calcium disodium edetate. Am J Dis Child 1987;141: 1256–1257. 7. Drug Evaluations, 6th Edition, American Medical Association, Saunders, Philadelphia, 1986, pp. 1637–1639. 8. Centers for Disease Control: Preventing lead poisoning in young children. Atlanta, GA, Department of Health and Human Services, 1985 Jan. 9. Finberg L, Rajagopal V. Diagnosis and treatment of lead poisoning in children. J Family Med 1985 April: 3–12. 10. Schardein JL, Sakowski R, Petrere J, et al. Teratogenesis studies with EDTA and its salts in rats. Toxicol Appl Pharmacol 1981; 61: 423–428. 11. Swenerton H, Hurley LS. Teratogenic effects of a chelating agent and their prevention by zinc. Science 1971; 173: 62–64. 12. American Hospital Formulary Service, Drug Information, 1988, pp. 1695–1698. 13. Markowitz ME, Rosen JF. Assessment of lead stores in children: Validation of an 8-hour CaNa2EDTA (Edetate Calcium Disodium) provocative test. J Pediatrics 1984;104: 337–341. 14. Piomelli S, Rosen JF, Chisolm JJ, et al. Management of childhood lead poisoning. J Pediatrics 1984; 105: 523–532. 15. Sachs HK, Blanksma LA, Murray EF, et al. Ambulatory treatment of lead poisoning: Report of 1,155 cases. Pediatrics 1970; 46: 389. 16. Chisolm JJ. The use of chelating agents in the treatment of acute and chronic lead intoxication in childhood. J Pediatrics 1968; 73: 1. 17. Coffin R, Phillips JL, Staples WI, et al. Treatment of lead encephalopathy in children. J Pediatrics 1966; 69: 198–206. 18. Chisolm JJ. Increased lead absorption and acute lead poisoning. Current Pediatric Therapy 12, Gillis and Kagan, editors, WB Saunders, Philadelphia, 1986, pp. 667–671. Distributed by: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816. Made in India Contacts For Media Inquiries: Marina Wissa, (201) 961 9013 mediainquiries@risingpharma.com For Customer Service Inquiries: Jason Eisner, (201) 961 9000 customerservice@risingpharma.com

Clinical ResultDrug Approval

29 Mar 2024

·www.prnewswire.com

Journal of Pharmaceutical Analysis (JPA) Studies Find Promising Drug Candidates

Researchers investigate the intricacies of various cellular processes and pathologies and identify compounds with untapped therapeutic potential XI'AN, China, March 29, 2024 /PRNewswire/ -- Understanding the underlying mechanisms of normal and pathological cellular processes is essential for developing new drugs. Fortunately, modern techniques and experimental methods have greatly accelerated progress. The latest issue of JPA features three articles in which candidate compounds for treating complex disorders were successfully identified, alongside their detailed mechanisms of action. Continue Reading Recent JPA studies identify, through detailed analyses of molecular mechanisms and cellular processes, three potential drug candidates for three different pathologies. The first study investigated the use of metformin (Met), a drug used to manage type II diabetes, for treating benign prostate hyperplasia (BPH). The article was published in Volume 14, Issue 1 of the journal in January 2024. The researchers first sought to shed light on how and which dysregulated sex steroid hormone-related pathways shape the pathological characteristics of BPH, and whether Met can restore these pathways. Through retrospective analysis of data from BPH patients and clinical assessment of serum and tissue samples, the researchers identified dihydrotestosterone (DHT) as a major contributor to BPH among dysregulated sex hormones. DHT promotes prostate cell proliferation by upregulating androgen receptors and forming YAP1-TEAD4 heterodimers. In vivo experiments showed that Met treatment restored sex hormone homeostasis and inhibited DHT-induced cell proliferation. "Our study provided strong evidence that Met might be a promising clinical therapeutic approach for the treatment of BPH," remark corresponding authors Prof. Qian Lu and Prof. Xiaoxing Yin. In the second study, scientists explored the role of epimedin B (EB), the main flavonoid in the Chinese herb Epimedium brevicornum Maxim., in melanogenesis. They expanded on previous findings showing EB's ability to induce melanogenesis and activate tyrosinase family of proteins (TYRs). Through comprehensive in vitro and in vivo experiments on human and animal cells, they uncovered how EB modulated TYRs, increased melanosome numbers, promoted maturation, and aided depigmentation and repigmentation. "Our data reveals that EB can stimulate the pigmentation function of TYRs, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries," comments corresponding authors Dr. Yiming Li and Prof. Huali Wu. Finally, in the third study, researchers investigated ferroptosis, a type of programmed cell death, and its role in nerve regeneration after peripheral nerve injury (PNI). They found that oxidative stress at the injury site not only triggered both apoptosis and ferroptosis in nearby neurons by increasing intracellular iron via the degradation of ferroportin by UBA52. Using the Drug Signatures Database, they identified hydralazine (HYD), a potent arterial vasodilator, as a potential UBA52 disruptor. Early HYD administration after PNI in vivo expedited axon regeneration and motor function recovery, partly by suppressing ferroptosis. "The potential clinical implementation of HYD may lead to a reduction in the prevalence of individuals with mild symptoms of nerve damage, consequently mitigating the societal burden," conclude corresponding authors Dr. Bing Xia, Prof. Zhuojing Luo, and Dr. Jinghui Huang. Further studies will hopefully clarify the intricate connections among cellular processes, diseases, and potential drugs, paving the way for precise and efficient therapies. Reference Titles of original papers Metformin: A promising clinSical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52 Journal: Journal of Pharmaceutical Analysis DOI 1. 2. 3. Media contact Mengjie Wang [email protected] +86-(0)29-88960092 SOURCE Journal of Pharmaceutical Analysis (JPA)

29 Aug 2023

·www.sciencedaily.com

A 'mini-brain' traces the link between concussion and Alzheimer's disease

Damage associated with Alzheimer's disease begins within hours after a concussion according to results from research that uses a 'mini-brain' lab on a chip device. How much time elapses between a blow to the head and the start of damage associated with Alzheimer's disease? A device that makes it possible to track the effects of concussive force on a functioning cluster of brain cells suggests the answer is in hours. The "traumatic brain injury (TBI) on a chip" being developed at Purdue University opens a window into a cause and effect that announces itself with the passage of decades but is exceedingly difficult to trace back to its origins. "We're basically creating a miniature brain that we can hit and then study," said Riyi Shi, lead researcher and the Mari Hulman George Endowed Professor of Applied Neuroscience in Purdue University's College of Veterinary Medicine. "We know there's a link between TBI and Alzheimer's; that's well established in clinical observation. But teasing out the basic essential pathway is not easy. With the TBI on a chip, we're able to test a lot of hypotheses that would be very difficult to do in living animals." In a study recently published in Lab on a Chip, a research team led by Shi subjected functioning clusters of cultured neurons from embryonic mice to three blows of 200 g-force, each approximating the higher end of what a football player receives in a single hit. The trauma leads to an immediate surge in production of acrolein -- a molecule associated with oxidative stress and neurodegenerative disease -- and a rise in misfolded clumps of the protein amyloid beta 42 (AB42), which is found in masses called plaques in the brains of people with Alzheimer's disease. Additional experiments traced the links between impact, acrolein and AB42. The device can also be used to test possible therapeutics, including drugs known to reduce acrolein levels. In the current study, Shi's team used the device to show that the drug hydralazine, a known acrolein scavenger that is approved by the U.S. Food and Drug Administration for lowering blood pressure, reduces the amount of acrolein and levels of misfolded AB42 produced in the cluster of neurons after a hit. Shi, who has a long history of studying neurodegenerative disease, acrolein and hydralazine, said the TBI on a chip enabled a finding he's sought over two decades of study. "Now that we know what's happening, is there something we can do about it? And the answer is yes," said Shi, who is also a member of the Purdue Institute for Integrative Neuroscience. "Acrolein is time-dependent; the longer it's there, the more AB42 aggregation it will cause. Here we show that if we lower acrolein with this drug, we can lower inflammation and AB42 aggregation." The device, custom-fabricated at the Purdue Center for Paralysis Research, uses a pendulum to deliver a specific g-force to a small chamber housing a cluster of a quarter million neurons supported by a bed of nutrients. A microelectronic array embedded in the chamber measures the electrical activity of the neurons, which will sustain functional firing patterns for several weeks, while a clear viewing port allows microscopic observation of the neurons. Researchers remove the cluster of neurons from the chamber at intervals to take specific biochemical measurements. "There's several unique things that we do here, but one of the biggest is that you can hit this chip without damaging it, so you can give an impact to a live model and continue to study it," Shi said. Shi began working on the device in graduate school, incorporating over the course of several decades features that make it possible to study the aftereffects of an initial blow. A 2022 paper in Nature Scientific Reports used the device to show the surge in acrolein that occurs after a hit, and Shi said the most recent findings hint at the power of the model. "Thanks to this device, people should know that when you get a concussion, you don't have 10 years before you will see damage," Shi said. "The clock starts ticking immediately, and if we want to do something about it, we need to act quickly." Within the first 24 hours after a hit, results show elevated levels of acrolein in the neuron clusters and a 350% increase in production of misfolded AB42. Shi said acrolein deforms normal AB42 by binding to sections of the protein that contribute to structural stability. Indeed, when the team conducted a simple experiment by combining large amounts of acrolein with normal purified AB42 suspended in fluid, they found elevated levels of misfolded AB42. The properly folded protein is sufficiently fragile that even subjecting normal purified AB42 in fluid (without acrolein) to an impact was enough to provoke misfolding. "This amyloid beta pathology started within hours, maybe immediately. That's never been heard of," Shi said. "It's like attacking the weight-bearing stud in a house wall. If you break that stud, of course the house is going to fall down." Shi was joined in the research by Purdue colleagues Edmond A. Rogers, first author, and co-authors Timothy Beauclair, Jhon Martinez, Shatha J. Mufti, David Kim, Siyuan Sun, Rachel L. Stingel, Nikita Krishnan and Jennifer Crodian, senior research associate at Purdue's Center for Paralysis Research, as well as Alexandra M. Dieterly of Charles River Laboratory. The study was supported by the state of Indiana, the National Institutes of Health and Plexon Inc. Moving forward, Shi said, he may be able to incorporate multiple additional features, which would allow the measurements of minute forces that cells experience during the blow, and biochemical testing -- like checking levels of acrolein -- without removing cells from the chamber.

100 Deals associated with Hydralazine Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D01302	Hydralazine Hydrochloride	C02DB02	DB01275

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Heart Failure	China	Shanghai ZhongXi Pharmaceutical Co. Ltd.	01 Jan 1995
Eclampsia	Japan	Sun Pharma Japan Ltd.	21 Feb 1968
Hypertensive Encephalopathy	Japan	Sun Pharma Japan Ltd.	21 Feb 1968
Hypertension	-	Novartis Pharma AG	01 Jan 1952

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Dystrophy, Macular	Phase 3	United States	MacuCLEAR, Inc.	01 Oct 2012

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04116112 (BEST-II, CTgov)	Phase 2	Thrombosis \| Stroke	120	Labetalol+Nicardipine+Hydralazine (Higher Systolic Blood Pressure (SBP) Target)	gzrmhvypaz(hroiueokhm) = ydbuyudbeu nyetmfzkxz (mdunfxgqpd, nulkwawezx - yctaldzvzo) View more	-	12 Oct 2023
NCT04116112 (BEST-II, CTgov)	Phase 2	Thrombosis \| Stroke	120	Labetalol+Nicardipine+Hydralazine (Lower SBP (<160 mmHg) Target)	gzrmhvypaz(hroiueokhm) = uwspbngwku nyetmfzkxz (mdunfxgqpd, smuvelceox - nzxrvvahut) View more	-	12 Oct 2023
ATS2023	Not Applicable	Pericardial Effusion	-	Hydralazine	bjrdcdepuk(wkgyttuibx) = positive fhhghixohw (dffwwilqtt ) View more	-	21 May 2023
ATS2023	Not Applicable	Cardiac Tamponade \| Lupus Erythematosus	-	Hydralazine	gxxhgsiwln(sggnymxhly) = Repeat CXR and bedside POCUS were concerning for pericardial effusion, with an echocardiogram report confirming impending tamponade ieibuurkog (zfzxjkiwiu ) View more	-	21 May 2023
ASN2022	Not Applicable	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ANA Homogneous pattern \| c-ANCA antibody \| p-ANCA antibody ... View more	-	Hydralazine	dqbruzhpya(tnrlwryefv) = presenting with acute renal failure njueadehrt (qwetfzmcir )	Negative	06 Nov 2022
ASN2022	Not Applicable	anti-histone antibodies \| anti-PLA2R	-	Hydralazine	jjttyrazxl(ngjzruyuwr) = rwxgzkgmbq nhakpvhyqy (ificfdbzfv ) View more	-	04 Nov 2022
ASN2022	Not Applicable	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis	-	Hydralazine	enolbeotdn(czydzcygup) = ftrggymtgd dzwzfzzshd (xqeolifdym, 6.8) View more	-	04 Nov 2022
ASN2022	Not Applicable	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis	-	IV Methylprednisolone	slcqtautwh(qwwoktmvgv) = ecsytlofsq tfscvugxcs (eyyhsbltoq )	-	04 Nov 2022
ASN2022	Not Applicable	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis	-	Hydralazine 100mg TID	bnfdcobqfo(zbwfyuolcw) = datfkdphvg iebfubxsxz (icbaujiaew )	-	03 Nov 2022
ATS2022	Not Applicable	-	-	Hydralazine	ujpbateowt(lsnwhydbsw) = Alloimmunization to certain blood group system antigens causes significant diagnostic and transfusion problems oqldadtcwy (yyehdqpylz )	-	15 May 2022
ASN2021	Not Applicable	Lupus Nephritis \| Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ANCA positivity \| histone antibody	-	Hydralazine	fuecvtbvkx(qvltidtusx) = persistent hemoptysis with worsening dyspnea, skin rash, and oral ulcers akncecccxc (zgchuhursu ) View more	Negative	27 Oct 2021
ASN2020	Not Applicable	-	-	Hydralazine	wgquecfeok(xekifuqttg) = ovztcgpzep rcpujxnrui (alnagniuaq )	-	19 Oct 2020
ASN2020	Not Applicable	-	-	IV Furosemide	wgquecfeok(xekifuqttg) = hsozexzpcq rcpujxnrui (alnagniuaq )	-	19 Oct 2020

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