化工社化工社 化学情報印刷レポート · 研究参考用
ベンゾナテート
エキサンギト · ベンゾノナチン · ベンツッシン · p-(ブチルアミノ)安息香酸2,5,8,11,14,17,20,23,26-ノナオキサオクタコサン-28-イル · テサロンCiba · ベンツッシンLoz · テッサロン · ベンゾノナンチン
識別子と物理属性
| CAS No. | 104-31-4 |
|---|---|
| 分子式 | C30H53NO11 |
| 平均分子量 | 603.7 g/mol |
| 単同位体質量 | 603.36186152 g/mol |
| SMILES | CCCCNc1ccc(C(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOC)cc1 |
| InChIKey | MAFMQEKGGFWBAB-UHFFFAOYSA-N |
| PubChem CID | 7699 |
| ChEMBL | CHEMBL1374379 |
| ChEBI | CHEBI:3032 |
| EC No. | 203-194-7 |
| DTXSID | DTXSID9022655 |
| 現地名 | ベンゾナテート |
化学・物理的性質
| XLogP | 2.4 |
|---|---|
| 極性表面積 | 121 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 12 |
| 回転可能結合数 | 33 |
| 重原子数 | 42 |
| 形式電荷 | 0 |
| 複雑度 | 565 |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15 |
| LogP（分配係数） | log Kow = 2.451.2 |
| Color/Form | Colorless to faintly yellow oil |
| 溶解度 | Soluble in most organic solvents except aliphatic hydrocarbons1.59e-03 g/Lクロロホルム（微量）、メタノール（微量） |
| Human Drugs | Breast FeedingLactationMilk, HumanAntitussive AgentsFDA approved drugs -> Active ingredient |
| Physical Description | Liquid |
| 沸点 | 649.0±55.0 °C(Predicted) |
| 密度 | 1.096±0.06 g/cm3(Predicted) |
| 貯蔵条件 | Refrigerator, under inert atmosphere |
| pKa（酸解離定数） | 2.20±0.39(Predicted) |
| 外観・状態 | 油 |
| 色 | ライトイエロー～ライトブラウン |
| BCS Class | 3 |
| InChI | 1S/C30H53NO11/c1-3-4-9-31-29-7-5-28(6-8-29)30(32)42-27-26-41-25-24-40-23-22-39-21-20-38-19-18-37-17-16-36-15-14-35-13-12-34-11-10-33-2/h5-8,31H,3-4,9-27H2,1-2H3 |
| InChIKey | MAFMQEKGGFWBAB-UHFFFAOYSA-N |
| SMILES | C(OCCOCCOCCOCCOCCOCCOCCOCCOCCOC)(=O)C1=CC=C(NCCCC)C=C1 |
| CAS データベース | 104-31-4(CAS DataBase Reference) |
安全性と法規制
| GHS 分類 | WarningH302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 火災の可能性 | This material is assumed to be combustible. |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including benzonatate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Toxic Combustion Products | Emits toxic fumes under fire conditions. |
| Hazard Classes and Categories | Acute Tox. 4 (50%) |
| 消火手順 | Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials. ... As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing. |
| 保管条件 | Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.Commercially available benzonatate liquid-filled capsules should be stored in tight, light-resistant containers at a controlled room temperature of 15-30 °C. |
| 清掃方法 | Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing vapor. Ventilate area and wash spill site. Place spillage in appropriately labeled container for disposal. |
| 処分方法 | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash. |
| Preventive Measures | SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.Engineering controls such as exhaust ventilation are recommended.As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling. |
| 相互作用 | Benzonatate is chemically related to anesthetic agents of the para-amino-benzoic acid class (e.g. procainetetracaine) and has been associated with adverse CNS effects possibly related to a prior sensitivity to related agents or interaction with concomitant medication. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ The signs and symptoms of overdose of benzonatate have been reported within 15-20 minutes. If capsules are chewed or dissolved in the mouth, oropharyngeal anesthesia will develop rapidly, which may cause choking and airway compromise. CNS stimulation may cause restlessness and tremors which may proceed to clonic convulsions followed by profound CNS depression. Convulsions, coma, cerebral edema and cardiac arrest leading to death have been reported within 1 hour of ingestion./SIGNS AND SYMPTOMS/ Accidental ingestion of Tessalon resulting in death has been reported in children below age 10. Signs and symptoms of overdose have been reported within 15-20 minutes and death has been reported within one hour of ingestion. If accidental ingestion occurs, seek medical attention immediately/CASE REPORTS/ A 12-month-old male presented to the emergency department of a rural hospital following ingestion of an unknown amount of benzonatate. Upon arrival, the child was seizing and in full cardiac arrest. Resuscitative measures were unsuccessful and the child died shortly after arriving at the emergency department./CASE REPORTS/ A 17-year-old woman with no previous medical history presented to the Emergency Department (ED) status post cardiac arrest. One to two hours prior, the patient had ingested at least ten 200 mg Tessalon capsules as part of a suicide attempt. The patient was sedated, intubated, and given magnesium as prophylaxis against recurrent dysrhythmias. Emergent gastric lavage was performed and well tolerated. A 24 hr hypothermia protocol with 6 hr cooling period was initiated. Toxicological studies, chest radiograph, and a computed tomography scan of the head were all unremarkable. The patient was admitted to the Pediatric Intensive Care Unit for further work-up and supportive care. The patient was extubated and able to follow some commands 1 week post-admission. The patient developed blindness and experienced generalized confabulations, which did not resolve. Ingestion of Tessalon, a seemingly innocuous and widely prescribed antitussive, may pose a risk to patients due to its potential for the rapid development of life-threatening adverse events and limited treatment options in the overdose setting.For more Human Toxicity Excerpts (Complete) data for Benzonatate (7 total), please visit the HSDB record page. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)BenzonatatevLess-DILI-concernNo matchDOI:10.1016/j.drudis.2016.02.015 |
| Populations at Special Risk | Safety and effectiveness in children below the age of 10 have not been established. Accidental ingestion resulting in death has been reported in children below age 10. Keep out of reach of children. |
| Probable Routes of Human Exposure | NIOSH (NOES Survey 1981-1983) has statistically estimated that 197 workers (59 of these were female) were potentially exposed to benzonatate in the US(1). |
| Antidote and Emergency Treatment | In case of overdose, seek medical attention immediately. Evacuate gastric contents and administer copious amounts of activated charcoal slurry. Even in the conscious patient, cough and gag reflexes may be so depressed as to necessitate special attention to protection against aspiration of gastric contents and orally administered materials. Convulsions should be treated with a short-acting barbiturate given intravenously and carefully titrated for the smallest effective dosage. Intensive support of respiration and cardiovascular-renal function is an essential feature of the treatment of severe intoxication from overdosage. Do not use CNS stimulants.Emergency and supportive measures. Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, arrhythmias, and anaphylaxis if they occur. ... Monitor vital signs and ECG for at least 6 hours /Anesthetics, local/.Decontamination. Parenteral exposure: Decontamination is not feasible. Ingestion:. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestins if activated charcoal can be given promptly. /Anesthetics, local/./SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/For more Antidote and Emergency Treatment (Complete) data for Benzonatate (6 total), please visit the HSDB record page. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| 水環境危害等級（WGK） | WGK 3 |
| 毒性 | LD50 oral in mouse: 400mg/kg |
| 危険等級 | Aquatic Chronic 3 |
| 貯蔵分類 | 11 - Combustible Solids |
| 有害物質データ | 104-31-4(Hazardous Substances Data) |
用途
説明
Benzonatate is a reversible voltage-gated sodium channel blocker. It blocks Nav1.7 currents in a concentration- and voltage-dependent manner (IC50s = 5.9 and 1.4 μM at holding potentials of -100 and -70 mV, respectively) and inhibits action potential firing in catecholamine A differentiated (CAD) cells. Benzonatate also blocks 80% of Nav1.3 currents in N1E-115 cells when used at a concentration of 100 μM. In vivo, benzonatate (0.85 mg/min) reduces the frequency, but has no effect on the amplitude, of the cough reflex in anesthetized dogs. Formulations containing benzonatate have been used as antitussive agents for the treatment of coughs.
来歴
Benzonatate is used to relieve cough. Benzonatate is in a class of medications called antitussives (cough suppressants). It works by reducing the cough reflex in the lungs and air passages. It was first synthesized in 1956 and was introduced as an antitussive in the United States in 1958.Availability worldwide is limited, with the drug remaining marketed only in the United States and Mexico. In 2023, it was the 122nd most commonly prescribed medication in the United States, with more than 5 million prescriptions. A 2023 systematic review found that there is inadequate evidence to support the effectiveness and safety of benzonatate for cough and highlighted rising safety concerns.
使用
Antitussive