化工社化工社 化学情報印刷レポート · 研究参考用
アモキサピン
アモキサン · 2-クロロ-11-ピペラジノジベンゾ[b,f][1,4]オキサゼピン · アモキサピン · 2-クロロ-11-(1-ピペラジニル)ジベンゾ[b,f][1,4]オキサゼピン · アモキサピン (JP17) · 13-クロロ-10-(ピペラジン-1-イル)-2-オキサ-9-アザトリシクロ[9.4.0.03,8]ペンタデカ-1(15),3,5,7,9,11,13-ヘプタエン · Amoxepine · amoxan
識別子と物理属性
| CAS No. | 14028-44-5 |
|---|---|
| 分子式 | C17H16ClN3O |
| 平均分子量 | 313.8 g/mol |
| 単同位体質量 | 313.09818981 g/mol |
| SMILES | Clc1ccc2c(c1)C(N1CCNCC1)=Nc1ccccc1O2 |
| InChIKey | QWGDMFLQWFTERH-UHFFFAOYSA-N |
| PubChem CID | 2170 |
| ChEMBL | CHEMBL1113 |
| ChEBI | CHEBI:2675 |
| EC No. | 237-867-1 |
| DTXSID | DTXSID7022598 |
| 現地名 | アモキサピン |
化学・物理的性質
| XLogP | 2.6 |
|---|---|
| 極性表面積 | 36.9 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 3 |
| 回転可能結合数 | 1 |
| 重原子数 | 22 |
| 形式電荷 | 0 |
| 複雑度 | 424 |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15 |
| LogP（分配係数） | 3.43.71 |
| 溶解度 | 1.71e-01 g/L34.4 [ug/mL] (The mean of the results at pH 7.4)メタノール: 可溶 |
| Human Drugs | Antidepressants -> Tricyclic antidepressants (TCA)Breast FeedingLactationMilk, HumanAntidepressive AgentsSerotonin Uptake InhibitorsFDA approved drugs -> Active ingredientPharmaceuticals |
| 融点 | 175-176175.5 °C175-1760C |
| Physical Description | Solid |
| Dissociation Constants | 8.71 |
| Collision Cross Section | 172.3 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: Antidepressants]170.2 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]165.42 Ų [M+K]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]171.2 Ų [M+H]+ [CCS Type: TW |
| 沸点 | 469.9±55.0 °C(Predicted) |
| 密度 | 1.2613 (rough estimate) |
| 屈折率 | 1.5800 (estimate) |
| 引火点 | 9℃ |
| 貯蔵条件 | Keep in dark place,Inert atmosphere,Room temperature |
| pKa（酸解離定数） | pKa 7.6 (Uncertain) |
| 外観・状態 | 個体 |
| 色 | ベンゼン/石油エーテルからの結晶 |
| Merck | 14,576 |
| 安定性 | Stable under recommended storage conditions., Stable Under Recommended Storage C |
| 主な用途 | 医薬品（低分子化合物） |
| InChI | 1S/C17H16ClN3O/c18-12-5-6-15-13(11-12)17(21-9-7-19-8-10-21)20-14-3-1-2-4-16(14)22-15/h1-6,11,19H,7-10H2 |
| InChIKey | QWGDMFLQWFTERH-UHFFFAOYSA-N |
| SMILES | Clc1ccc2Oc3ccccc3N=C(N4CCNCC4)c2c1 |
| CAS データベース | 14028-44-5(CAS DataBase Reference) |
| NISTの化学物質情報 | Amoxapine(14028-44-5) |
化学的特性
Crystalline Solid
安全性と法規制
| GHS 分類 | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 45 reports by companies from 2 notifications to the ECHA C&L Inventory. |
|---|---|
| 規制情報 | Hazard Traits - Developmental ToxicityDibenzb,f1,4oxazepine, 2-chloro-11-(1-piperazinyl)-: Does not have an individual approval but may be used under an appropriate group standard |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Treatment | Treatment of amoxapine overdosage should be symptomatic and supportive, but with special attention to prevention or control of seizures. If the patient is conscious, induced emesis followed by gastric lavage with appropriate precautions to prevent pulmonary aspiration should be accomplished as soon as possible. Following lavage, activated charcoal may be administered to reduce absorption, and repeated administrations may facilitate drug elimination. An adequate airway should be established in comatose patients and assisted ventilation instituted if necessary. Seizures may respond to standard anticonvulsant therapy such as intravenous diazepam and/or phenytoin. The value of physostigmine appears less certain. Status epilepticus, should it develop, requires vigorous treatment. (L1712) |
| Hepatotoxicity | Liver test abnormalities occur in a small proportion of patients on long term therapy with amoxapine, but elevations are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury without jaundice have been reported due to amoxapine, but have been quite rare. Published cases have been mild, anicteric and asymptomatic. The onset of injury was within 1 to 4 weeks of starting, and the pattern of serum enzyme elevations was hepatocellular. Immunoallergic features and autoantibody formation were not present. |
| 有害作用 | The common adverse effects of amoxapine therapy include, but are not limited to, insomnia, palpitations, tachycardia, hypotension, and constipation. Furthermore, research has indicated that amoxapine may trigger hypomanic states in individuals with underlying bipolar disorder. Amoxapine has been observed to induce noradrenaline-mediated contraction of the urethra in guinea pigs and rats in various laboratory studies, leading to elevated urethral resistance. In addition, the drug has been associated with instances of painful ejaculations relieved by the administration of tamsulosin. Notably, tricyclic antidepressants (TCAs), including amoxapine, are correlated with an increased risk of seizures, especially in older patients and those with epilepsy. Therefore, it is recommended to use SSRIs or SNRIs in patients with a history of epilepsy and seizures. |
| 暴露経路 | Oral, rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single doser. |
| 毒性の概要 | Signs and Symptoms of OverdoseAmoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT). |
| Signs and Symptoms | Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects, particularly grand mal convulsions, occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Renal failure may develop two to five days after toxic overdose in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomuolysis and myolobinurla is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)AmoxapineAmbiguous-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | HQ4025500 |
| 輸送番号（UN） | 3249 |
| 毒性 | LD50 in mice (mg/kg): 122 i.p.112 orally (Howell, 1972) |
| 税関コード | 2934990002 |
| 危険文句（R） | 22 |
| 危険表示 | Xn |
| 安全措置（S） | 36 |
| 危険等級 | 6.1(b)Acute Tox. 4 Oral |
| 包装等級 | III |
| 貯蔵分類 | 11 - Combustible Solids |
用途
用途
三環系抗うつ作用化合物です。 モノアミン神経伝達物質再取り込み阻害作用 を示します。
用途
三環系抗うつ作用化合物です。 モノアミン神経伝達物質再取り込み阻害作用 を示します。
説明
Amoxapine is a tetracyclic antidepressant with a wide range of pharmacological effects. It inhibits norepinephrine and serotonin reuptake, binding the respective transporters with Kd values of 16 and 58 nM. It has also been shown to act as either an antagonist or inverse agonist at serotonin 5-HT2A, 2B, 2C, 3, 6, 7 (Kis = 1 and 2 nM for 5-HT2A and 5-HT2C, respectively), dopamine D2, 3, 4 (Kd = 160 nM for D2), α1-adrenergic (Kd = 50 nM), and histamine H1 (Kd = 25 nM) receptors.
使用
Amoxapine is intended more for relieving symptoms in patients with neurotic or situational depression. It has a number of serious side effects.
一般的な説明
Consideration of the structure of amoxapine, 2-chloro-11-(1-piperazinyl)dibenz-[b,f] [1,4]oxazepine (Asendin), reinforcesthe fact that many antidepressants are very closelyrelated to antipsychotics. Indeed, some, including amoxapine,have significant effects at D2 receptors. The Nmethyl–substituted relative of amoxapine is the antipsychoticloxapine (Loxitane). The 8-hydroxy metabolite ofamoxapine is reportedly active as an antidepressant and asa D2 receptor blocker.