カルバマゼピン 化学特性,用途語,生産方法
外観
白色～わずかにうすい黄色、結晶性粉末～粉末
溶解性
クロロホルムに溶けやすく、エタノール(95)及びアセトンにやや溶けにくく、水及びジエチルエーテルに極めて溶けにくい。
解説
カルバマゼピン,精神運動発作に有効な抗てんかん薬。化学構造的にも薬理学的にも三環系抗うつ剤，特に塩酸オピプラモールに類似する。臨床的には三叉神経痛やこれに関連した神経痛，難治性のしゃっくりにも有効であるが，作用機序は明らかでない。副作用として骨髄機能抑制 (再生不良性貧血，白血球減少症，血小板減少性紫斑病などが起る) ，黄疸，循環器系障害 (高血圧を伴う乏尿，左心室不全，循環虚脱) ，アレルギー，嘔吐などがあるが，非常に有用な薬物である。
用途
ナトリウム透過性抑制作用を 示します。
用途
ナトリウム透過性抑制作用を
示します。
効能
鎮痛薬, 抗てんかん薬
商品名
テグレトール (サンファーマ)
確認試験
(１) 本品0.1gに硝酸2mLを加え，水浴上で3分間加熱する
とき，液はだいだい赤色を呈する．
(２) 本品0.1gに硫酸2mLを加え，水浴上で3分間加熱する
とき，液は黄色を呈し，緑色の蛍光を発する．
(３) 本品に紫外線を照射するとき，強い青色の蛍光を発す
る．
( ４ ) 定量法で得た液につき，紫外可視吸光度測定法
により吸収スペクトルを測定し，本品のスペクトル
と本品の参照スペクトルを比較するとき，両者のスペクトル
は同一波長のところに同様の強度の吸収を認める．
定量法
本品を乾燥し，その約50mgを精密に量り，エタノー
ル(95)に溶かし，正確に250mLとする．この液5mLを正確
に量り，エタノール(95)を加えて正確に100mLとする．こ
の液につき，紫外可視吸光度測定法により試験を行
い，波長285nm付近の吸収極大の波長における吸光度Aを測
定する．
カルバマゼピン(C
15H
12N
2O)の量(mg)＝A／490 × 50000
純度試験
(１) 溶状 本品1.0gをクロロホルム10mLに溶かすとき，
液は無色～微黄色澄明である．
(２) 酸 本品2.0gに水40mLを正確に加え，15分間よく振
り混ぜた後，ガラスろ過器(G3)でろ過する．ろ液10mLを正
確に量り，フェノールフタレイン試液1滴及び0.01mol/L水
酸化ナトリウム液0.50mLを加えるとき，液の色は赤色であ
る．
(３) アルカリ (2)のろ液10mLを正確に量り，メチルレッ
ド試液1滴及び0.01mol/L塩酸0.50mLを加えるとき，液の色
は赤色である．
(４) 塩化物 本品0.25gをアセトン30mLに溶かし，
希硝酸6mL及び水を加えて50mLとする．これを検液とし，
試験を行う．比較液は0.01mol/L塩酸0.20mLにアセトン
30mL，希硝酸6mL及び水を加えて50mLとする(0.028％以
下)．
(５) 重金属 本品2.0gをとり，第2法により操作し，
試験を行う．比較液には鉛標準液2.0mLを加える(10ppm以
下)．
(６) 類縁物質 本品0.25gをとり，クロロホルム10mLを
正確に加えて溶かし，試料溶液とする．別にイミノジベンジ
ル5.0mgをとり，クロロホルムに溶かし，正確に100mLと
し，標準溶液とする．これらの液につき，薄層クロマトグラ
フィーにより試験を行う．試料溶液及び標準溶液
10μLずつを薄層クロマトグラフィー用シリカゲルを用いて
調製した薄層板にスポットする．次にトルエン／メタノール
混液(19：1)を展開溶媒として約10cm展開した後，薄層板を
風乾する．これに二クロム酸カリウム・硫酸試液を均等に噴
霧するとき，試料溶液から得た主スポット以外のスポットは，
標準溶液から得たスポットより濃くない．
貯法
容器 気密容器．
乾燥減量
0.5％以下(1g，105℃，2時間)．
強熱残分
0.1％以下(1g)．
説明
Carbamazepine is a synthetic iminostilbene derivative structurally
similar to imipramine, a tricyclic antidepressant. While
unrelated structurally, carbamazepine shares a similar therapeutic
action with phenytoin. Carbamazepine was first discovered
in 1953 by Swiss chemist Walter Schindler. Throughout the
1960s, antimuscarinic was used and marketed for trigeminal
neuralgia and as an anticonvulsant. By the 1970s, it was being
used as a mood stabilizer for patients with bipolar disorder.
化学的特性
White or off-white crystalline powder. Soluble in ethanol, acetone, propylene glycol, insoluble in water. Odorless and tasteless.
使用
Carbamazepine (CBZ) is a first generation anticonvulsant and mood stabilizing compound that has been used as a therapeutic in the context of neuropathic pain, epilepsy, and affective disorders. It exerts its effects by blocking voltage-gated sodium channels (IC50 = 640 μM), making fewer of these channels available to subsequently open, which leads to decreased high-frequency repetitive firing of action potentials. The estimated IC50 values for inhibition of Nav1.7-, Nav1.3-, and Nav1.8-type channels by CBZ following prolonged inactivation have been reported as 406, 900, and 138 μM, respectively. CBZ can also inhibit L-type Ca2+ channels (IC50 = 974 μM) and has been shown to potentiate GABAA receptors (IC50 >3 mM).
定義
ChEBI: Carbamazepine is a dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant. It has a role as an anticonvulsant, an EC 3.5.1.98 (histone deacetylase) inhibitor, a mitogen, a glutamate transporter activator, an antimanic drug, an analgesic, a non-narcotic analgesic, an environmental contaminant, a xenobiotic, a drug allergen and a sodium channel blocker. It is a dibenzoazepine and a member of ureas.
生物学の機能
Carbamazepine has become a major drug in the treatment
of seizure disorders. It has high efficacy, is well tolerated
by most patients, and exhibits fewer long-term
side effects than other drugs.
Oral absorption of carbamazepine is quite slow and
often erratic. Its half-life is reported to vary from 12 to
60 hours in humans.The development of blood level assays
has markedly improved the success of therapy with
this drug, since serum concentration is only partially
dose related. Carbamazepine is metabolized in the liver,
and there is evidence that its continued administration
leads to hepatic enzyme induction. Carbamazepine-
10,11-epoxide is a pharmacologically active metabolite with significant anticonvulsant effects of its own.
一般的な説明
Certified pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to pharmacopeia primary standards.
Carbamazepine is a tricyclic lipophilic compound, with mild anticholinergic activity. It is widely used as an antiepileptic drug for the treatment of simple and complex partial tonic-clonic seizures.
作用機序
In animals, the profile of antiseizure properties for CBZ is similar to that of phenytoin. CBZ is effective in the maximal
electroshock (MES) test (electrically induced seizure test) but is ineffective against pentylenetetrazole-induced seizures. It is
not effective for absence or myoclonic seizures and, indeed, may exacerbate their onset. Like phenytoin, CBZ acts on
voltage-dependent sodium channels to prevent the spread of seizures. CBZ depresses synaptic transmission in the reticular
activating system, thalamus, and limbic structures. In a double-blind, crossover study in patients whose seizures were not
controlled completely by combinations of AED, CBZ was equal in efficacy to phenobarbital and phenytoin in controlling seizure
frequency, and side effects were minimal.
臨床応用
Carbamazepine is an effective agent for the treatment
of partial seizures and generalized tonic–clonic
seizures; its use is contraindicated in absence epilepsy.
Carbamazepine is also useful in the treatment of
trigeminal neuralgia and is an effective agent for the
treatment of bipolar disorders.
薬物相互作用
Carbamazepine may be affected by other medicines, such as blood clot preventers and antibiotics. It may also interact with medications used to treat bipolar disorder. Some medications can decrease carbamazepine levels and others can increase carbamazepine levels. Valproate may increase carbamazepine-10,11-epoxide levels, while carbamazepine may decrease the levels of various medications including corticosteroids, clozapine, and lamotrigine. It is important to inform your doctor if you are taking any of these medicines to avoid potential interactions and to ensure carbamazepine works effectively.
Taking carbamazepine with other medicines and herbal supplementsWhat drug-drug interactions should you be vigilant for when someone is prescribed carbamazepinehttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c13bc0b8-7900-4ef4-98ed-e1315a08d95d
環境運命予測
Carbamazepine is both an important anticonvulsant in therapeutic
doses and a powerful proconvulsant in overdose. The
therapeutic anticonvulsant mechanism is primarily related to
blockade of presynaptic voltage-gated sodium channels.
Blockade of the sodium channels is believed to inhibit the
release of synaptic glutamate and possibly other neurotransmitters.
Carbamazepine is also a powerful inhibitor of the
muscarinic and nicotinic acetylcholine receptors, N-methyl-Daspartate
(NMDA) receptors, and the central nervous system
(CNS) adenosine receptors. In addition, carbamazepine is
structurally related to the cyclic antidepressant imipramine
and in massive overdose, it may affect cardiac sodium
channels.
カルバマゼピン 上流と下流の製品情報
原材料
準備製品