Succinylcholine Chloride

Cholinesterase is a class of glycoprotein that is present in the body in various isoenzyme forms. It can be generally divided into true cholinesterase and pseudocholinesterase. True cholinesterase, also known as acetylcholinesterase, mainly exists in the cholinergic nerve synaptic cleft, especially in the folds of the post-synaptic membrane of the motor nerve end plate, but also in cholinergic neurons and red blood cells. This enzyme has the highest activity and specificity for physiological concentrations of Acetylcholine (Ach). One enzyme molecule can hydrolyze 3 x 10 molecules of Ach, and it is often simply referred to as cholinesterase. Pseudocholinesterase is widely found in neuroglial cells, plasma, liver, kidney, and intestines. It has lower specificity for Ach and can hydrolyze other cholinergic esters, such as succinylcholine. The active center on the surface of the cholinesterase protein molecule has two binding sites for acetylcholine, which are the negatively charged anionic site and the esterase site. The esterase site contains an acidic site composed of serine hydroxyl groups and a basic site composed of a histidine imidazole ring, which are bound by hydrogen bonds, enhancing the nucleophilic activity of the serine hydroxyl groups, making them easier to bind with acetylcholine. The process of cholinesterase hydrolysis of acetylcholine can be divided into three steps: ① the quaternary ammonium ion head with a positive charge in the acetylcholine molecule structure is bound to the anionic site of the cholinesterase by electrostatic attraction. Simultaneously, the carbonyl carbon in the acetylcholine molecule is covalently bound to the hydroxyl group of the serine of the cholinesterase esterase site, forming a complex of acetylcholine and cholinesterase. ② The complex of acetylcholine and cholinesterase then splits into choline and acetylated cholinesterase. ③ Acetylated cholinesterase is rapidly hydrolyzed, releasing acetic acid, and restoring the enzyme’s activity. Cholinesterase Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 24 Sep 2023, there are a total of 9 Cholinesterase drugs worldwide, from 13 organizations, covering 10 indications, and conducting 27 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the target Cholinesterase reveals that Alpha Cognition, Inc., Hyundai Pharmaceutical Co., Ltd., and Galantos Pharma GmbH are the companies growing fastest under this target. The highest stage of development is Phase 3, with drugs targeting Alzheimer's Disease. Small molecule drugs are progressing rapidly, indicating a focus on this drug type. The countries/locations developing fastest include Japan, China, South Korea, and Canada. China has shown significant progress in the development of drugs targeting Cholinesterase. Overall, the competitive landscape for the target Cholinesterase is dynamic, with ongoing R&D efforts and a focus on Alzheimer's Disease and other relevant indications. The Globally Approved Cholinesterase Inhibitor: Pyrantel PamoatePyrantel Pamoate is a small molecule drug that falls under the therapeutic area of infectious diseases. It targets cholinesterase, an enzyme involved in the breakdown of acetylcholine, a neurotransmitter. The drug is primarily indicated for the treatment of several parasitic infections, including Ancylostomiasis, Trichostrongylosis, Ascariasis, and Enterobiasis. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Pyrantel Pamoate was first approved in China in January 1984, making it one of the earliest drugs in its class to receive regulatory approval. The drug is manufactured by Pfizer AS, a well-known pharmaceutical organization with a strong presence in the global market. It is important to note that Pyrantel Pamoate has achieved the highest phase of approval globally. Ancylostomiasis, also known as hookworm infection, is caused by parasitic worms that attach themselves to the intestinal wall and feed on blood. Trichostrongylosis is another parasitic infection caused by nematodes that primarily affect livestock but can also infect humans. Ascariasis is caused by the roundworm Ascaris lumbricoides and is one of the most common parasitic infections worldwide. Enterobiasis, commonly known as pinworm infection, is caused by the parasitic worm Enterobius vermicularis and is highly prevalent, especially in children. The approval of Pyrantel Pamoate in China suggests its effectiveness in treating these parasitic infections prevalent in the region. The drug's mechanism of action, targeting cholinesterase, disrupts the nervous system of the parasites, leading to their paralysis and subsequent elimination from the body. Given the drug's long history of approval and its indication for multiple parasitic infections, Pyrantel Pamoate has likely established itself as a reliable treatment option in the field of infectious diseases. Its approval in the global market further highlights its potential to address the significant burden of parasitic infections in various populations. In conclusion, Pyrantel Pamoate is a small molecule drug developed by Pfizer AS, targeting cholinesterase and primarily indicated for the treatment of Ancylostomiasis, Trichostrongylosis, Ascariasis, and Enterobiasis. With its earliest approval in China in 1984, the drug has achieved the highest phase of approval globally. Its approval suggests its potential as an effective treatment option for parasitic infections prevalent in the region.

ADLARITY is FDA approved for patients with Alzheimer's Dementia Data reinforce favorable skin tolerability and adhesion of first ever once-weekly transdermal system offering continuous delivery of Alzheimer's dementia drug donepezil BOSTON, Sept. 12, 2023 /PRNewswire/ -- Corium, LLC, a commercial-stage biopharmaceutical company leading the development and commercialization of novel neuroscience therapies, announced today the publication of data reinforcing that ADLARITY (donepezil transdermal system) demonstrated favorable skin tolerability and adhesion in a placebo-controlled trial with healthy volunteers. ADLARITY, developed by Corium, is the first and only U.S. FDA approved once-weekly, donepezil transdermal system for patients with mild, moderate and severe dementia of the Alzheimer's type. The data appear in the October-December 2023 issue of the peer-reviewed Alzheimer's Disease and Associated Disorders journal. Continue Reading ADLARITY continuously delivers consistent doses of donepezil through the skin, enabling a generally favorable overall gastrointestinal (GI) side effect profile. Donepezil, an acetylcholinesterase inhibitor and the active ingredient in the oral medication Aricept®, is the most prescribed Alzheimer's dementia medication in the United States. ADLARITY (donepezil transdermal system) demonstrated favorable skin tolerability and adhesion in a placebo-controlled trial with healthy volunteers. Tweet this In the double-blind Phase 1 study (NCT03397862), 256 healthy adults received ADLARITY on one side of their back and a placebo patch on the other side. For three weeks, the investigators placed the patches once weekly on the same location—a condition in the study exaggerating real world use by placing the patches in the same place for three weeks successively. In contrast, during routine patient use, ADLARITY's instructions for use advise patients not to place the patch in the same location for at least two weeks (14 days) after removal from that location. After three weeks, the tested ADLARITY patches caused none-to-minimal skin irritation in most subjects. "These important data show that the once-weekly ADLARITY skin patch had good adhesion and overall mild to no skin irritation despite the exaggerated conditions used during testing," said lead author Marwan N. Sabbagh, MD, Professor of Neurology. "The results grow our understanding of ADLARITY's safety profile and provide additional information that should be helpful to clinicians when considering the only weekly skin patch formulation of donepezil for their Alzheimer's patients." "The skin irritation results showed a trend of better skin tolerability in study participants aged 65 or greater compared to those under 65, which is clinically relevant for the indicated patient population," said Charles Oh, MD, Chief Medical Officer of Corium. "ADLARITY is an example of the value and commitment Corium brings to developing treatment options that address unmet needs of people with neurological conditions." Study examines skin irritation, sensitization, and adherence Investigators measured any skin irritation at study days eight, 15 and 22 using a combined skin irritation score (CSIS) from the Dermal Response Scale and an Other Effects Scale, as recommended by the FDA. After three weeks, the tested ADLARITY patches caused none-to-minimal skin irritation in most subjects, scoring an average 0.55 points (±0.78) of a possible maximum of 7 points using a calculation of the mean CSIS scores across the three weekly measures. The placebo patches scored 0.19 (±0.35), indicating no skin irritation. Of the 198 participants who completed the study, four had potential sensitization to ADLARITY, and none to the placebo patches. In general, on a weekly basis, the patches had good adhesion and essentially no lift from the skin. During the study 12 patches, seven of 735 ADLARITY and five of 736 placebo, detached. The study did not identify any safety concerns of either a local or systemic nature. Treatment emergent adverse events (TEAEs) occurred in more than 10 percent of the patients including application-site pruritis (40.2 percent), headache (18.4 percent), nausea (18.0 percent), abnormal dreams (18.0 percent), muscle spasms (16.8 percent), and insomnia (10.2 percent). Of the 256 participants, 11 participants (4.3 percent) discontinued the study because of TEAEs. One participant discontinued because of application-site reactions [discharge, erythema (red skin), and edema (swelling)] and 10 discontinued because of increased blood pressure (>140 mmHg systolic) considered mild in severity. Physicians interested in receiving more information or resources can request field representative support via . Corium also is supporting patient access to ADLARITY under CoriumCares™, a patient access and support program offering information about access and copay assistance for eligible commercially-insured patients. More information is available at or (800) 433-4893. Marwan N. Sabbagh, MD, Philip Mathew, PhD, and Alan Blau, PhD. A Randomized Double-blind Study to Assess the Skin Irritation and Sensitization Potential of a Once-weekly Donepezil Transdermal Delivery System in Healthy Volunteers. Alzheimer Disease & Associated Disorders ():10.1097/WAD.0000000000000587, September 11, 2023. | DOI: 10.1097/WAD.0000000000000578. Available at . About Alzheimer's Disease Alzheimer's disease is a progressive and irreversible brain disorder. It involves changes in brain tissue including abnormal buildup of proteins as well as loss of neuron function. The resulting damage leads to the loss of remembering, reasoning, and thinking abilities. Dementia ranges in severity from mild, when it is just beginning to affect a person's functioning, to moderate, to severe, when the person must depend on others for the basic activities of day-to-day life. Patients with Alzheimer's disease also develop changing to their swallowing during early to mid-stage disease that can progress to dysphagia, or swallowing impairment, in later stages. Dysphagia increases their risk of dehydration, dehydration, or aspiration, which frequently leads to aspiration pneumonia, a common cause of death among these patients. The related behavioral changes also include the loss of independence in activities of daily living and self-care. An estimated 6.5 million Americans older than 65 were living with Alzheimer's disease in 2022, with a possible rise to 14 million by 2060. Globally, more than 55 million people have dementia, and Alzheimer's disease may account for 60 to 70 percent of patients, according to the World Health Organization. The U.S. Centers for Disease Control and Prevention estimates that in 2021 more than 11 million Americans provided an estimated 16 billion hours of unpaid care for patients with Alzheimer's disease. Indication and Important Safety Information for ADLARITY (donepezil transdermal system) INDICATION ADLARITY is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer's type. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS ADLARITY is contraindicated in patients with known hypersensitivity to donepezil or to piperidine derivatives or with a history of allergic contact dermatitis with use of ADLARITY. WARNINGS AND PRECAUTIONS Application site skin reactions: ADLARITY may cause skin application-site reactions. These reactions are not necessarily indicative of sensitization; however, allergic contact dermatitis may occur and should be suspected if application-site reactions spread beyond the size of the transdermal system, there is evidence of a more intense local reaction, and symptoms do not significantly improve within 48 hours of transdermal system removal. Anesthesia: ADLARITY is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. Cardiovascular conditions: ADLARITY may have vagotonic effects on the sinoatrial and atrioventricular nodes. These effects may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil. Nausea and vomiting: ADLARITY may cause diarrhea, nausea, and vomiting. Although in most cases these effects have been transient, some cases lasted 1 to 3 weeks. Patients should be monitored closely during initiation and titration of ADLARITY. Peptic ulcer disease and gastrointestinal bleeding: ADLARITY may increase gastric acid secretion. Patients should be monitored closely for active or occult gastrointestinal bleeding, especially those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Genitourinary conditions: Although not observed in clinical trials of ADLARITY, bladder outflow obstruction may occur. Seizures: ADLARITY is believed to have some potential to cause generalized convulsions; however, seizure activity may also be a manifestation of Alzheimer's disease. Pulmonary conditions: ADLARITY should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease. ADVERSE REACTIONS The most common side effects of ADLARITY (>3%) were headache (15%), application site pruritus (9%), muscle spasms (9%), insomnia (7%), abdominal pain (6%), application site dermatitis (6%), constipation (6%), diarrhea (4%), application site pain (4%), dizziness (4%), abnormal dreams (4%) and skin laceration (4%). DRUG INTERACTIONS Cholinesterase inhibitors, including donepezil, have the potential to interfere with the activity of anticholinergic medications. A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol. For additional safety information, click here for the Prescribing Information and Patient Information. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. About Corium Corium, LLC, is a biopharmaceutical company that is leading the development and commercialization of neuroscience therapies that provide physicians with innovative treatment options for patients, their families, and their caregivers. Corium is commercializing two U.S. FDA approved products, ADLARITY and AZSTARYS, in the U.S., and has licensed each for development and commercialization in certain territories outside the U.S. For further information, please visit . Contact: Corium, LLC Gartman PR [email protected] 202-413-4226 SOURCE Corium, LLC