Dopamine vs. Norepinephrine in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure and Systemic Hypotension Due to Pulmonary Hypertension: A Pilot Trial

This pilot randomized clinical trial compares dopamine and norepinephrine as first-line vasoactive therapies in term and late preterm neonates with pulmonary hypertension associated with hypoxemic respiratory failure and systemic hypotension. Systemic hypotension is a common and clinically significant complication of persistent pulmonary hypertension of the newborn (PPHN) and frequently requires vasopressor support to maintain adequate systemic perfusion. Dopamine is commonly used in this setting; however, prior animal experimental and clinical data suggest it may increase pulmonary vascular resistance, potentially worsening right ventricular afterload and hypoxemia. Norepinephrine may preferentially increase systemic vascular resistance with less effect on the pulmonary circulation. This study evaluates short-term hemodynamic and oxygenation responses following initiation of dopamine or norepinephrine.

Start Date01 Jun 2026

Sponsor / Collaborator

University of California, Davis

[+1]

NCT07379710

/ Not yet recruitingPhase 4IIT

Concomitant Use of Norepinephrine With Ephedrine Versus Norepinephrine Alone to Maintain Arterial Blood Pressure During Spinal Anesthesia for Cesarean Delivery, a A Prospective Double-blinded Study.

We hypothesize that the addition of ephedrine to norepinephrine infusion could decrease the incidence of post spinal hypotension(PSH) in parturient undergoing C.S under spinal anesthesia and minimize the changes in heart rate

Start Date01 Feb 2026

Sponsor / Collaborator

Cairo University

ChiCTR2600117221

/ Not yet recruitingEarly Phase 1IIT

Impact of Intraoperative Cerebral Oximetry Monitoring on Postoperative Delirium in Elderly Patients Undergoing Spinal Surgery

Start Date01 Feb 2026

Sponsor / Collaborator

The Second Affiliated Hospital of Chongqing Medical University

[+1]

100 Clinical Results associated with Norepinephrine Bitartrate

100 Translational Medicine associated with Norepinephrine Bitartrate

100 Patents (Medical) associated with Norepinephrine Bitartrate

78,106

Literatures (Medical) associated with Norepinephrine Bitartrate

31 Dec 2026·ANNALS OF MEDICINE

Effects of phenylephrine and norepinephrine with restrictive infusion on oxygenation during one-lung ventilation for lung surgery: a randomized controlled trial

Article

Author: Xu, Longhe ; Liu, Yi ; Liu, Yongzhe ; Li, Jiaxin ; Liu, Xiangjie

OBJECTIVE:

This study compared the effects of norepinephrine or phenylephrine combined with restrictive infusion on the oxygenation during thoracoscopic one-lung ventilation (OLV).

METHODS:

Ninety patients were randomly divided into three groups: the norepinephrine group (Group N), the phenylephrine group (Group P), and the control group (Group C). Arterial partial pressure of oxygen (PaO₂) and intrapulmonary shunt fraction (Qs/Qt) were measured with patients in lateral positions during two-lung ventilation (TLV) at 10 min (T1), and during OLV at 15 min (T2) and 45 min (T3). Lung tissue samples were analyzed for endothelin and COX-2 levels after surgery.

RESULTS:

At T3, Group P had significantly higher PaO₂ and lower Qs/Qt than Groups N and C (all p < 0.05), with no significant differences between Groups N and C (all p > 0.05). Compared to T1, Groups N and C showed significantly lower PaO₂ and higher Qs/Qt at T2 and T3 (all p < 0.05), with no significant differences in PaO₂ and Qs/Qt at T3 compared with T2 (all p > 0.05). Group P patients had lower PaO₂ and higher Qs/Qt at T2 and T3 compared to T1 (all p < 0.05), but at T3, PaO₂ increased and Qs/Qt decreased compared to T2 (all p < 0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p < 0.05).

CONCLUSION:

Combining phenylephrine with restrictive infusion during OLV improved oxygenation by increasing PaO₂, decreasing Qs/Qt, and raising endothelin and COX-2 levels in lung tissue, thereby enhancing the HPV effect.

01 Dec 2026·JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

The discovery of monoamine oxidase inhibitors: virtual screening and in vitro inhibition potencies

Article

Author: Petzer, Anél ; Shaw, Maryké ; Petzer, Jacobus P ; Crous, Chantalle ; Cloete, Theunis T

Abstract:

The monoamine oxidase (MAO) enzymes are mitochondrial flavoenzymes that catalyse the oxidative deamination of neurotransmitter amines such as serotonin, norepinephrine and dopamine. Inhibitors of the MAOs are well-known antidepressant and antiparkinsonian agents, and act by reducing MAO-mediated metabolism of neurotransmitters in the brain. The present study attempted to identify compounds that inhibit the MAOs by virtual screening of existing drugs listed in the DrugBank using the Discovery Studio life science software. To identify the combinations of docking and scoring functions that most accurately identify known MAO inhibitors, the enrichment factor (EF 10% ) and area under the receiver operating characteristic curve (ROC-AUC) were evaluated. As a third validation metric, ligands that have been complexed with the MAOs were redocked and the root mean square deviation (RMSD) from the co-crystallized orientation was measured. The LibDock/LigScore 2 combination yielded the best results for both MAO-A (EF 10% : 5.20, ROC-AUC: 0.82) and MAO-B (EF 10% : 7.47, ROC-AUC: 0.89). Among the top 100 hits, ten compounds were selected and evaluated as in vitro inhibitors of human MAO. Guanabenz (IC 50 = 3.46 µM) and proflavine (IC 50 = 0.223 µM) were found to be the most potent MAO-A inhibitors. These compounds also inhibited MAO-B with IC 50 values of 8.49 and 34.3 µM, respectively. Kinetic analysis showed a competitive mode of MAO-A inhibition for guanabenz (K i = 0.16 µM) and proflavine (K i = 0.066 µM). These results show that the validated virtual screening protocol is a useful tool to aid in the discovery of MAO inhibitors. Graphical abstract

01 Aug 2026·BIOELECTROCHEMISTRY

RNA aptamer-modified gold-plated carbon fiber microelectrodes for selective dopamine sensing

Article

Author: Bache, Christian Meinert ; Shipovskov, Stepan ; Ewing, Andrew ; Ferapontova, Elena E ; López Mujica, Michael E J

Specific electroanalysis of neurotransmitters in the brain, bloodstream, cerebrospinal fluid (CSF), or at the cellular level critically depends on the availability of miniaturized electrodes for aptasensing. Yet, with electrode miniaturization, sensitivity of analysis and limits of detection (LOD) can be compromised. Here, we adapted the RNA-aptamer-based macroelectrode assay for dopamine to the microelectrode format, by using gold-plated carbon fiber microelectrodes (CFE), modified via thiol chemistry with cysteamine and an RNA aptamer, for specific dopamine detection. The sensitivity of analysis with gold-plated cylindrical microelectrodes improved 90-fold, to 9.75 μA μM^-1 cm^-2 (at +0.100 V) vs. 108 nA μM^-1 cm^-2 (at optimal +0.185 V) shown with gold disk macroelectrodes, with LOD being 60 and 100 nM, in PBS and in artificial CSF, respectively. Yet, epinephrine interfered at 0.1 V. At 0.05 V, the sensitivity dropped to 4.62 μA μM^-1 cm^-2 but the RNA-aptamer/cysteamine-modified CFEs demonstrated excellent selectivity for dopamine over epinephrine, norepinephrine, L-DOPA, DOPAC, and uric and ascorbic acids. These findings suggest a straightforward strategy for constructing biospecific aptamer-based microelectrodes. However, in matrices more complex than CSF, such as serum, dopamine oxidation was inhibited. Therefore, effective monitoring of dopamine levels in blood using aptamer microelectrodes will likely require the use of protective membranes.

News (Medical) associated with Norepinephrine Bitartrate

31 Dec 2025

·axsometherapeuticsinc.gcs-web.com

Axsome Therapeutics Announces FDA Acceptance and Priority Review of Supplemental New Drug Application for AXS-05 for the Treatment of Alzheimer’s Disease Agitation

FDA grants AXS-05 Priority Review designation and sets PDUFA action goal date of April 30, 2026 NEW YORK, Dec. 31, 2025 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s supplemental New Drug Application (NDA) for AXS-05 (dextromethorphan HBr and bupropion HCl) for the treatment of Alzheimer’s disease agitation, and has granted the application Priority Review designation. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2026. Priority Review is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. A Priority Review designation means the FDA’s goal is to take action on an application within 6 months, compared to 10 months under standard review. “We are very pleased the FDA has accepted and granted priority review to our supplemental NDA for AXS-05 for the treatment of Alzheimer’s disease agitation,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “Up to 76% of people with Alzheimer’s disease experience agitation, representing a significant unmet medical need for patients and their caregivers, and currently there is a dearth of approved treatments. We look forward to continuing to work with the FDA for the remainder of the review.” The FDA previously granted Breakthrough Therapy designation for AXS-05 for the treatment of Alzheimer’s disease agitation in June 2020. A Breakthrough Therapy designation is granted to potentially expedite development and review timelines for a promising investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for a serious or life-threatening condition. The supplemental NDA is the culmination of a comprehensive clinical development program of AXS-05 in Alzheimer’s disease agitation, including four randomized, double-blind, controlled Phase 3 clinical trials and a long-term safety trial. About Alzheimer’s Disease Agitation Alzheimer’s disease (AD) is the most common form of dementia, affecting approximately 7 million people in the United States.1 Agitation is reported in up to 76% of patients with AD and is characterized by emotional distress, verbal and physical aggressiveness, disruptive irritability, and disinhibition.1,2 AD agitation has been associated with accelerated cognitive decline, increased caregiver burden, earlier nursing home placement, and increased mortality.3 About AXS-05 AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor under development for the treatment of Alzheimer’s disease (AD) agitation and smoking cessation. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive NMDA receptor antagonist, also known as a glutamate receptor modulator, and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is covered by a robust patent estate extending out to at least 2043. AXS-05 was granted U.S. FDA Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020. AXS-05 (AUVELITY®) is approved in the U.S. for the treatment of major depressive disorder in adults. AXS-05 is not approved by the FDA for Alzheimer’s disease agitation. About Axsome Therapeutics Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes. Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder, excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, and migraine, and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States. Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish. For more information, please visit us at www.axsome.com and follow us on LinkedIn and X. Forward Looking Statements Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the commercial success of the Company’s SUNOSI®, AUVELITY®, and SYMBRAVO® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates; the Company’s ability to fund additional clinical trials to continue the advancement of the Company’s product candidates; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, the Company’s product candidates, including statements regarding the timing of any NDA submission; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the Company’s ability to successfully resolve any intellectual property litigation, and even if such disputes are settled, whether the applicable federal agencies will approve of such settlements; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the commercialization of SUNOSI, AUVELITY, and SYMBRAVO and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; the Company’s ability to convert sales to recognized revenue and maintain a favorable gross to net sales; unforeseen circumstances or other disruptions to normal business operations arising from or related to domestic political climate, geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances. Investors: Ashley Dong Director, Investor Relations (929) 687-1614 adong@axsome.com Media: Darren Opland Senior Director, Corporate Communications (929) 837-1065 dopland@axsome.com References Source: Axsome Therapeutics, Inc.

Priority ReviewPhase 3NDADrug ApprovalBreakthrough Therapy

02 Dec 2025

·www.businesswire.com

Fresenius Kabi Expands Operating Room Portfolio with New Simplist ® Prefilled Syringes

LAKE ZURICH, Ill.--(BUSINESS WIRE)--Fresenius Kabi, part of the global healthcare company Fresenius, and a leading provider of essential medicines and medical technologies, announced today it has introduced two new products in its Simplist® portfolio of ready-to-administer prefilled syringes: Simplist® Ephedrine Sulfate Injection, USP and Simplist® Succinylcholine Chloride Injection, USP. Both medications are used in anesthesia and critical care, and their introduction extends the Simplist line’s use into operating rooms, supporting clinicians with safe, efficient and reliable medication delivery. Fresenius Kabi has expanded its Simplist® ready-to-administer portfolio, introducing new presentations that extend its use into operating rooms and support clinicians in anesthesia and critical care. Simplist Succinylcholine Chloride Injection, USP, is a paralytic used in addition to general anesthesia for intubation and during mechanical ventilation in pediatric and adult patients. Simplist Ephedrine Sulfate Injection, USP is indicated for the treatment of clinically important hypotension (low blood pressure) during anesthesia. “As part of our commitment to simplify medication delivery and improve patient safety, the expansion of our Simplist portfolio into the operating room demonstrates how we’re supporting anesthesiologists and nurse anesthetists in their vital work,” said Arun Verma, president of Fresenius Kabi Region U.S. and member of the Executive Leadership Team at Fresenius Kabi AG. “These ready-to-administer medications are designed to help clinicians throughout the hospital by helping to reduce complexity, help minimize waste, and reduce the number of drug-preparation steps where errors can occur.” About the Products: Simplist Succinylcholine Chloride Injection, USP is available in 100 mg per 5 mL (20 mg per mL) and 200 mg per 10 mL (20 mg per mL) strengths. It offers an 18-month shelf life and is stored in a refrigerator at 36°F (2°C) to 46°F (8°C). The single dose prefilled syringes are stable for up to 14 days at room temperature without loss of potency. Simplist Ephedrine Sulfate Injection, USP is available in 25 mg per 5 mL (5 mg per mL) and 50 mg per 10 mL (5 mg per mL) presentations. It can be stored at room temperature and has a 24-month shelf life. Both prefilled syringes are manufactured and prepared by Fresenius Kabi, eliminating the need for assembly or dilution at the point of care to simplify medication administration, enhance workflow efficiency, and support best practices in medication administration safety. To learn more about Fresenius Kabi’s expanding manufacturing and other operations in the U.S., visit www.MoreInAmerica.com. IMPORTANT SAFETY INFORMATION Succinylcholine Chloride Injection, USP WARNING: VENTRICULAR DYSRHYTHMIAS, CARDIAC ARREST, AND DEATH FROM HYPERKALEMIC RHABDOMYOLYSIS IN PEDIATRIC PATIENTS CONTRAINDICATIONS In patients with skeletal muscle myopathies In patients with known hypersensitivity to succinylcholine After the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury In patients with a personal or familial history or suspected genetic susceptibility to malignant hyperthermia WARNINGS AND PRECAUTIONS Anaphylaxis: Severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine, have been reported. Some cases have been life-threatening and fatal. Take necessary precautions, such as the immediate availability of appropriate emergency treatment. Risk of Death due to Medication Errors: Unintended administration of Succinylcholine Chloride Injection may result in paralysis, respiratory arrest and death. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. Hyperkalemia: Succinylcholine Chloride Injection may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia. Malignant Hyperthermia: Malignant hyperthermia may occur, especially in individuals with known or suspected susceptibility based on genetic factors or family history. Discontinue triggering agents, administer intravenous dantrolene sodium, and apply supportive therapies. Bradycardia: Intravenous bolus administration may result in profound bradycardia or, rarely asystole. The incidence is higher following a second dose of succinylcholine. Pretreatment with anticholinergic agents (e.g. atropine) may reduce the occurrence of bradyarrhythmias. ADVERSE REACTIONS Adverse reactions reported with succinylcholine are cardiac arrest, malignant hyperthermia, arrhythmias, bradycardia, tachycardia, hypertension, hypotension, hyperkalemia, prolonged respiratory depression or apnea. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Drugs that May Enhance the Neuromuscular Blocking Action of Succinylcholine: promazine, oxytocin, aprotinin, certain non-penicillin antibiotics, quinidine, β-adrenergic blockers, procainamide, lidocaine, trimethaphan, lithium carbonate, magnesium salts, quinine, chloroquine, isoflurane, desflurane, metoclopramide, terbutaline, and drugs that reduce plasma cholinesterase activity. INDICATIONS AND USAGE Succinylcholine Chloride Injection is a depolarizing neuromuscular blocker indicated in adults and pediatric patients: As an adjunct to general anesthesia To facilitate tracheal intubation To provide skeletal muscle relaxation during surgery or mechanical ventilation This Important Safety Information does not include all the information needed to use Succinylcholine Chloride Injection, USP safely and effectively. Please see full prescribing information, including BOXED WARNING, for Succinylcholine Chloride Injection, USP 100 mg per 5 mL and 200 mg per 10 at www.fresenius-kabi.com/us. Ephedrine Sulfate Injection, USP WARNINGS AND PRECAUTIONS Pressor Effects with Concomitant Use with Oxytocic Drugs: Pressor effect of sympathomimetic pressor amines is potentiated. Tachyphylaxis and Tolerance: Repeated administration of ephedrine may cause tachyphylaxis. ADVERSE REACTIONS Most common adverse reactions during treatment: nausea, vomiting, and tachycardia. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Interactions that Augment Pressor Effect: clonidine, oxytocin and oxytocic drugs, propofol, monoamine oxidase inhibitors (MAOIs), and atropine. Monitor blood pressure. Interactions that Antagonize the Pressor Effect: Antagonistic effects with α-adrenergic antagonists, β-adrenergic antagonists, reserpine, quinidine, mephentermine. Monitor blood pressure. Guanethidine: Ephedrine may inhibit the neuron blockage produced by guanethidine, resulting in loss of antihypertensive effectiveness. Monitor blood pressure and adjust the dosage of pressor accordingly. Rocuronium: Ephedrine may reduce the onset time of neuromuscular blockade when used for intubation with rocuronium if administered simultaneously with anesthetic induction. Be aware of this potential interaction. No treatment or other interventions are needed. Epidural anesthesia: Ephedrine may decrease the efficacy of epidural blockade by hastening the regression of sensory analgesia. Monitor and treat the patient according to clinical practice. Theophylline: Concomitant use of ephedrine may increase the frequency of nausea, nervousness, and insomnia. Monitor patient for worsening symptoms and manage symptoms according to clinical practice. Cardiac glycosides: Giving ephedrine with a cardiac glycoside, such as digitalis, may increase the possibility of arrhythmias. Carefully monitor patients on cardiac glycosides who are also administered ephedrine. INDICATIONS AND USAGE Ephedrine Sulfate Injection is an alpha- and beta-adrenergic agonist and a norepinephrine-releasing agent that is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia. This Important Safety Information does not include all the information needed to use Ephedrine Sulfate Injection, USP safely and effectively. Please see full prescribing information, for Ephedrine Sulfate Injection, USP at www.fresenius-kabi.com/us.” About Fresenius Kabi As a global healthcare company, Fresenius Kabi is Committed to Life. The company’s products, technologies, and services are used for the therapy and care of patients with critical and chronic conditions. With more than 41,000 employees and present in more than 100 countries, Fresenius Kabi’s expansive product portfolio focuses on providing access to high-quality and lifesaving essential medicines and technologies. In Biopharma, Fresenius Kabi offers cutting-edge biosimilars for autoimmune diseases and oncology. With leading market positions in Clinical Nutrition, a broad portfolio of enteral and parenteral products makes a distinct difference in patients’ nutritional status. In MedTech, the company provides vital infusion pumps, cell and gene therapy devices, disposables, and more. Fresenius Kabi is a global leader in supplying blood collection bags and devices, supporting blood banks and health care facilities worldwide. The company’s I.V. Generics and Fluids for infusion therapy help save millions of lives every year, in emergency medicine, surgery, oncology, and intensive care. Fresenius Kabi takes a holistic approach to health care and uniquely combines experience, expertise, innovation, and dedication – making a difference in the lives of 450 million patients annually. With the #FutureFresenius strategy, the company is developing, producing, and selling new products and technologies and aspires to expand its position as a leading global provider of therapies, improve patient care, generate sustainable value for stakeholders – shaping the future of healthcare. Fresenius Kabi is part of the Fresenius Group, founded in 1912, along with Helios and Quirónsalud. As ONE team, the companies in the Fresenius Group are committed to providing lifesaving and life-changing healthcare solutions on a global scale. For more information, please visit www.fresenius-kabi.com/us. To learn about U.S. career opportunities at Fresenius Kabi, visit us at www.fresenius-kabi.com/us/join-us and follow us on LinkedIn and Facebook. This release contains forward-looking statements that are subject to various risks and uncertainties. Future results could differ materially from those described in these forward-looking statements due to certain factors, e.g., changes in business, economic and competitive conditions, regulatory reforms, results of clinical trials, foreign exchange rate fluctuations, uncertainties in litigation or investigative proceedings, and the availability of financing. Fresenius Kabi does not undertake any responsibility to update the forward-looking statements in this release.

25 Nov 2025

·www.otsuka.co.jp

Otsuka Pharmaceutical Submits New Drug Application to U.S. FDA for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults

RSS Centanafadine is an investigational compound for the treatment of ADHD in children, adolescents, and adults. It is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). In four pivotal Phase 3 clinical trials evaluating the efficacy and safety of centanafadine across pediatric and adult patient populations, centanafadine demonstrated statistically significant efficacy for the core symptoms of inattention and hyperactivity-impulsivity in ADHD. Clinical and preclinical data suggest centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence. ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity. Although historically seen as a childhood disorder, research suggests that many individuals diagnosed with ADHD in childhood continue to experience symptoms into adulthood, with some patients experiencing significant impairment. ADHD is often not diagnosed until adulthood, with an estimated 15.5 million adults in the U.S. currently diagnosed. Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Otsuka Pharmaceutical Development & Commercialization, Inc. announce the filing of a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for centanafadine, once daily extended release capsules, a novel norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI), for the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. The NDA submission is supported by results from four pivotal Phase 3 clinical trials evaluating the efficacy and safety of centanafadine across patient populations1,2,3. "As an innovator in mental health, we are pleased to take this important step forward in the hope of providing a novel treatment option to patients living with ADHD," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "Centanafadine represents a first in class mechanism of action among available ADHD therapies, and if approved, may expand the range of options available to those managing this complex condition. We are grateful to the patients and caregivers for their participation in these trials." In Phase 3 clinical studies with children, adolescents, and adults, centanafadine demonstrated statistically significant and clinically meaningful improvements in ADHD symptoms compared with placebo, as measured by the ADHD Rating Scale-5 (ADHD-RS-5) in adolescents and children, and the ADHD Investigator Symptom Rating Scale (AISRS) in adults. Centanafadine was generally well tolerated across studies, with the most common adverse events including decreased appetite, nausea, rash, fatigue, abdominal pain, and somnolence in children and adolescents, and decreased appetite and headache in adults1,2,3. About the Phase 3 Clinical Trial Program The Phase 3 program for centanafadine provides a robust clinical evaluation of the first investigational NDSRI ADHD therapy. The clinical program consists of four different pivotal Phase 3 trials that evaluated the efficacy and safety of centanafadine across children, adolescents, and adults1,2,3. The pivotal Phase 3 trial in children (NCT05428033) was a randomized, double-blind, three-arm, fixed-dose study evaluating the efficacy, safety, and tolerability of centanafadine in children aged 4 to 12 years with ADHD. Participants received a weight-based high dose, low dose, or placebo for 6 weeks. The primary endpoint was the change from baseline in ADHD-RS-5 total score at Week 6. The high-dose group demonstrated statistically significant improvement versus placebo, while the low-dose group did not reach statistical significance. Centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence, with the most frequently reported adverse events including decreased appetite, rash, and vomiting1. The pivotal Phase 3 trial in adolescents (NCT05257265) was a randomized, double-blind, three-arm, fixed-dose study designed to evaluate the efficacy, safety, and tolerability of centanafadine in adolescents aged 13 to 17 years with ADHD. Participants received either a high dose, low dose, or placebo over a 6-week treatment period. The primary endpoint was change from baseline in the ADHD Rating Scale-5 (ADHD-RS-5) total score at Week 6. The high-dose group achieved statistically significant and clinically meaningful reductions in ADHD symptoms compared with placebo. Centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence, with the most common adverse events including decreased appetite, nausea, headache, and rash2. The two pivotal Phase 3 trials in adults (NCT03605680, NCT03605836) were randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of centanafadine sustained-release (SR) tablet in adults aged 18 to 55 years with ADHD. Participants received either centanafadine 200 mg/day, 400 mg/day, or placebo over a 6-week treatment period. The primary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Week 6. Both centanafadine dose groups demonstrated statistically significant and clinically meaningful improvements versus placebo. In both studies, centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence, with the most common adverse events including decreased appetite and headache3. About Attention-Deficit Hyperactivity Disorder (ADHD) ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity4. It affects approximately 7 million children in the U.S. and an estimated 15.5 million adults, according to the Centers for Disease Control and Prevention (CDC)5,6. About Centanafadine Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). Clinical studies have shown that centanafadine significantly reduces core symptoms of ADHD in children, adolescents, and adults, with a favorable safety and tolerability profile and low potential for abuse. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide. For further information, please visit www.otsuka.co.jp/en/ 1 References 1 Ward, Caroline L., et al. "Efficacy and safety of centanafadine for ADHD treatment in children: A randomized clinical trial." Pediatrics Open Science, vol. 1, no. 3, 1 July 2025, pp. 1-11, https://doi-org.libproxy1.nus.edu.sg/10.1542/pedsos.2024-000349. 2 Ward, Caroline L., Ann C. Childress, et al. "Centanafadine for attention-deficit/hyperactivity disorder in adolescents: A randomized clinical trial." Journal of the American Academy of Child & Adolescent Psychiatry, July 2025, https://doi-org.libproxy1.nus.edu.sg/10.1016/j.jaac.2025.06.023. 3 Adler, Lenard A., et al. "Efficacy, safety, and tolerability of Centanafadine sustained-release tablets in adults with attention-deficit/hyperactivity disorder." Journal of Clinical Psychopharmacology, vol. 42, no. 5, 2 June 2022, pp. 429-439, https://doi-org.libproxy1.nus.edu.sg/10.1097/jcp.0000000000001575. 4 American Psychiatric Association (2022). Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev). 5"Data and Statistics on ADHD." Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/adhd/data/index.html. 6 "Facts about ADHD in Adults." Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/adhd/php/adults/.

Clinical ResultPhase 3NDA

100 Deals associated with Norepinephrine Bitartrate

External Link

KEGG	Wiki	ATC	Drug Bank
D05206	Norepinephrine Bitartrate	C01CA03	DB00368

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Shock	Japan	Long Grove Pharmaceuticals LLC	24 Apr 1984
Anesthesia	United States	Hospira, Inc.	13 Jul 1950
Heart Arrest	United States	Hospira, Inc.	13 Jul 1950
Hypotension	United States	Hospira, Inc.	13 Jul 1950
Myocardial Infarction	United States	Hospira, Inc.	13 Jul 1950
Pheochromocytoma	United States	Hospira, Inc.	13 Jul 1950
Poliomyelitis	United States	Hospira, Inc.	13 Jul 1950
Sepsis	United States	Hospira, Inc.	13 Jul 1950

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04789330 (VEGA-1, CTgov)	Phase 4	Anesthesia \| Hypotension	3,626	Norepinephrine (Norepinephrine)	yvffkqiafm = aqhgahskat ungpicmoxa (lnwdfclaft, itjvihqkxw - fgytldpmoq) View more	-	18 Dec 2025
				Phenylephrine (Phenylephrine)	yvffkqiafm = ncixejblht ungpicmoxa (lnwdfclaft, kfeoexwaex - fuqzkyudrv) View more
NCT06158022 (Pubmed \| Drug Des Devel Ther)	Not Applicable	-	60	Norepinephrine	zzcpeoxcqw(sfjorogzal) = ntotpyggnf xmfzfacntz (mfmdnsdsht, 0.07 - 0.08)	Positive	01 Nov 2025
				Phenylephrine	zzcpeoxcqw(sfjorogzal) = dwlznjblqb xmfzfacntz (mfmdnsdsht, 0.85 - 0.95)
NCT05506319 (Pubmed \| Med Intensiva (Engl Ed))	Phase 4	Shock, Septic	-	Norepinephrine reduction	ltsqjrdspc(ayepgmpmqv) = nzhgbvggvz xrtpvdlhqq (wlehiuispn )	-	01 Oct 2025
				Vasopressin reduction	ltsqjrdspc(ayepgmpmqv) = vafznfzmux xrtpvdlhqq (wlehiuispn )
NCT05997303 (Pubmed \| Br J Anaesth)	Phase 4	High-Risk Pregnancy	71	Continuous norepinephrine infusion	hfvhajvvta(cvbqwmfjdp): P-Value = <0.001	Positive	01 Oct 2025
				Manual bolus norepinephrine administration
NCT05521152 (Pubmed \| Anaesth Crit Care Pain Med)	Phase 3	Biliary Atresia	-	Norepinephrine infusion	gbhxgptkza(lhovlxmwam) = lvansslslo fmkhvorfvt (xdwuoqquvm )	Positive	01 May 2025
				Placebo saline infusion	gbhxgptkza(lhovlxmwam) = jdzghdsbmj fmkhvorfvt (xdwuoqquvm )
NCT05931601 (EU CT ID 2023-504584-16-00, Pubmed \| Scand J Trauma Resusc Emerg Med)	Phase 3	Shock \| Hypotension	320	Early initiated noradrenaline	caotgutlsk(mlvtwueigv) = yqhhtxxuaq vnrupwbpus (tyjfeijlip ) View more	Positive	07 Apr 2025
NCT04501861 (CTgov)	Phase 3	Heart Diseases	153	Vasopressin (The Use of Vasopressin)	uheyexgyhi(gwszwehvbx) = dfwhpptlvx idrdvpipyu (bjtzdswmhn, 0.086) View more	-	09 Jan 2025
				Norepinephrine (The Use of Norepinephrine)	uheyexgyhi(gwszwehvbx) = aubwuzixct idrdvpipyu (bjtzdswmhn, 0.094) View more
NCT05133817 (Pubmed) Manual	Not Applicable	Anesthesia \| Hypotension	-	Prophylactic norepinephrine 0 µg/kg/min	pemzizakky(iuehmzjvvj) = iwsdhuiorz zruqcaiyon (qukkossikl ) View more	Positive	01 Jun 2024
				prophylactic norepinephrine 0.025 µg/kg/min	pemzizakky(iuehmzjvvj) = haubeoinzh zruqcaiyon (qukkossikl )
NCT04701190 (Pubmed \| J Clin Med)	Phase 4	Hypotension	192	Zero-Bolus High-Infusion (Group ZBHI)	ovlxcztlaq(uytqnboodu) = ukoufglyje eoeyfgbfoh (omtjwnocan )	Positive	10 Oct 2023
NCT03822091 (Pubmed \| Indian J Gastroenterol)	Phase 3	Hepatorenal Syndrome	-	Terlipressin	zehzhwhnku(fagwzlmqto) = vgxxzcucex dsjgfxzxab (brainjiuii ) View more	-	05 May 2023
				Terlipressin and Noradrenaline	zehzhwhnku(fagwzlmqto) = eljsysqfop dsjgfxzxab (brainjiuii ) View more

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