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Products Intro: Product Name:Carbamazepine
Purity:90%+ Package:10mg, 25mg, 50mg, 100mg, Other scale please email Remarks:5H-Dibenzo[b,f]azepine-5-carboxamide
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Products Intro: Product Name:carbamazepine
Purity:99% Package:100g/ bag, 2 kg/ bag, 25kg/ carton or as required Remarks:white to off-white solid

Carbamazepine manufacturers

  • Carbamazepine
  • $50.00 / KG
  • 2022-01-27
  • CAS:298-46-4
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  • Purity: 99.9%
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  • Carbamazepine
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  • 2022-01-25
  • CAS:298-46-4
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  • Purity: 99.5%
  • Supply Ability: 1000kg
  • Carbamazepine
  • $10.00 / KG
  • 2022-01-20
  • CAS:298-46-4
  • Min. Order: 1KG
  • Purity: 99%
  • Supply Ability: 500tons/month

Related articles

  • Uses of Carbamazepine
  • Carbamazepine is a synthetic iminostilbene derivative structurally similar to imipramine, a tricyclic antidepressant. While un....
  • Dec 8,2021
Carbamazepine Basic information
Overview Indication Dosage and administration Plasma levels monitoring Cautions Pharmacodynamics Interactions Special populations Mode of action Psychiatric use Adverse reactions and precaution References
Product Name:Carbamazepine
Synonyms:Oxcarbazepine IMpurity A;CarbaMazepine (D10, 98%);CarbaMazepine-13C6;Carbamazepine solution ;CARBAMAZEPIN;CARBAMAZEPINE;ANBROMINE;5H-DIBENZ[B,F]AZEPINE-5-CARBOXAMIDE
Product Categories:TEGRETOL;Pharmaceutical raw material;Pharmaceutical Chemicals;Intermediates & Fine Chemicals;Aromatics;Isotope Labelled Compounds;Pharmaceutical;Acids and Derivatives;Heterocycles;Active Pharmaceutical Ingredients;APIs;Pharmaceuticals
Mol File:298-46-4.mol
Carbamazepine Structure
Carbamazepine Chemical Properties
Melting point 191-192 °C (lit.)
Boiling point 378.73°C (rough estimate)
density 1.1099 (rough estimate)
refractive index 1.5906 (estimate)
Fp 9℃
storage temp. 2-8°C
solubility 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: soluble29mg/mL
form Crystals
color Almost white
Water Solubility pract. insoluble
Merck 14,1781
CAS DataBase Reference298-46-4(CAS DataBase Reference)
NIST Chemistry ReferenceCarbamazepine(298-46-4)
EPA Substance Registry System5H-Dibenz[b,f]azepine-5-carboxamide (298-46-4)
Safety Information
Hazard Codes Xn,T,F
Risk Statements 42/43-22-20/21/22-39/23/24/25-23/24/25-11
Safety Statements 37-24-22-36/37/39-36-45-36/37-16
RIDADR UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany 2
RTECS HN8225000
HS Code 29339900
Hazardous Substances Data298-46-4(Hazardous Substances Data)
ToxicityLD50 orally in mice, rats: 3750, 4025 mg/kg (Stenger, Roulet)
MSDS Information
Carbamazepine English
ACROS English
Carbamazepine Usage And Synthesis
OverviewCarbamazepine (CBZ) is an irninostilbene derivative, structurally similar to the tricyclic antidepressants. Chemically. CBZ is a neutral, liposoluble compound that can easily pass the bloodlbrain barrier and other membranes in the body. Developed and marketed for the treatment of epileptic seizures and trigeminal neuralgia, CBZ has been utilized more and more frequently in the last decade to treat psychiatric disorders.
Carbamazepine was first evaluated as a potential treatment in manic depressive psychosis by Takezaki and Hanaoka (1971)[1], and Okuma et al. (1973)[2]. In 1979, Okuma et al.[3] performed the first double-blind trial of carbamazepine in comparison with the antipsychotic chlorpromazine in mania and found that 70% and 60% of patients improved respectively. A further placebo-controlled double-blind study replicated the antimanic properties of carbamazepine under controlled circumstances (Ballenger and Post, 1980). There have since been many studies demonstrating the efficacy of carbamazepine in treating the acute manic and depressive symptoms of bipolar disorder, as well as in prophylaxis[4, 5].

Figure 1 the chemical structure of carbamazepine

Carbamazepine is a first- generation antiepileptic drug (AED) known with the proprietary brand name of Tegretol® (Novartis, Basel) in the UK and USA (Fig. 3.2). Oxcarbazepine is a second- generation AED supplied under the proprietary brand name of Trileptal® (Novartis, Basel) in the UK and USA (Fig. 3.3). Eslicarbazepine is a third- generation AED sold under the proprietary brand names of Zebinix® (Eisai, Hatfield) in the UK and Aptiom® (Sunovion, Marlborough, MS) in the USA.
IndicationCarbamazepine has been used to treat many types of epilepsies since the early sixties[6]. The psychotropic properties of the drug were soon recognized and prompted studies in psychiatric disorders. Today, the main indications for CBZ in psychiatry are the treatment of acute manic states and the prophylaxis of recurrence in bipolar disorders[7]. The clinical studies reviewed consistently reported a CBZ success rate in acute manic states and recurrence prophylaxis in bipolar disorders ranging from 50 to 65%. More recent works confirmed the success rate in acute manic states[8], whereas data for the long-term prophylaxis of recurrence were more variable, and in general less positive[9]. Post et al. (1993) [10] suggested that poor long-term CBZ efficacy might be due to tolerance development and, on the basis of the CBZ action in experimental models. Speculated that periods of drug "holiday" may restore its efficacy. A similar warning has been reported for the long-term prophylactic efficacy of lithium[11].
Evidence of some positive action of CBZ in unipolar depression has also been reported[12]. More recently. Cullen et al. (1991) [13] retrospectively analyzed 16 melancholic patients who received CBZ alone or in combination with other psychotropic drugs. Seven patients had a moderate to marked improvement, but treatment had to be discontinued in five due to side effects. Stuppaeck et al. (1993) [14], in open observations in 15 patients with unipolar depression, concluded that CBZ had a positive effect in 11 patients.
Other psychiatric syndromes for which CBZ has been proved or suggested to be useful include aggressive agitation in demented patients[15]. Super-sensitivity psychosis[16], and alcohol[17] and benzodiazepine withdrawal syndromes[18]. In panic disorders, CBZ has been reported to attenuate panic attacks in subjects with underlying EEG abnormalities[19]. However, in the only controlled trial in 14 patients with panic disorders, CBZ was no better than placebo[20]. Recommendations
  • Seizure types: first line (generalized tonic- clonic seizures, focal seizures), adjunctive (focal seizures), contraindicated (generalized tonic- clonic seizures if there are absence or myoclonic seizures, or if juvenile myoclonic epilepsy is suspected, tonic/ atonic seizures, absence seizures, myoclonic seizures).
  • Epilepsy types: first line (epilepsy with generalized tonic- clonic seizures only, benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late- onset childhood occipital epilepsy), adjunctive (benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late- onset childhood occipital epilepsy), contraindicated (absence syndromes, juvenile myoclonic epilepsy, idiopathic generalized epilepsy, Dravet syndrome, Lennox– Gastaut syndrome).
  • Psychiatry: prophylaxis of manic- depressive phases in patients with bipolar disorder unresponsive to lithium therapy; treatment of alcohol withdrawal symptoms (unlicensed).
  • Neurology: treatment of paroxysmal pain in trigeminal neuralgia and diabetic neuropathy (unlicensed).
Dosage and administrationCarbamazepine dosages employed in the various pathologies are similar: in most cases therapeutic effects are obtained at doses of 10 to 20 mg/kg/day. Age has only a limited effect on CBZ disposition, but children may need a slightly higher dosage (in mg/kg). No dosage adjustments are required in relation to patient's sex or other genetic factors. Treatment should be started at low dosages (3 - 5 mg/kg/day) and increased progressively by a similar amount every 5-7 days, until the desired clinical effect is obtained or persistent side effects appear. This approach will determine the lowest effective (or the maximum tolerated) dose and reduce the incidence of dose-dependent side effects, which are more frequent and more troublesome for the patient at the beginning of therapy[15]. If tolerance is poor but the drug seems to be clinically effective, an even slower titration may prove useful. Treatment of acute manic states, however, may require a faster titration at the cost of an increased frequency of side effects[16]. A daily dose administered in conventional tablets or oral suspension should be divided into 3-4 intakes to avoid excessive fluctuations of plasma concentration; alternatively, slow-release preparations can be used. In some countries a chewable tablet formulation (100 mg) is available, which may be convenient in children[13].
  • Epilepsyimmediate release: 100– 200 mg od/ bd, increased by 100– 200 mg every 14 days; usual maintenance 800– 1200 mg daily, in divided doses (max. 2000 mg daily).
  • Epilepsyprolonged release: 50– 200 mg bd, increased by 100– 200 mg every 14 days; usual maintenance 800– 1200 mg daily, divided into two doses (max. 2000 mg daily).
  • Bipolar disorderimmediate release: 400 mg daily, in divided doses, increased by 100– 200 mg every 14 days; usual maintenance 400– 600 mg daily, in divided doses (max. 1600 mg daily).
  • Bipolar disorderprolonged release: 200 mg bd, increased by 100– 200 mg every 14 days; usual maintenance 200– 300 mg bd (max. 1600 mg daily).
If stopping carbamazepine, patients with bipolar disorder need to reduce the dose gradually over a period of at least 4 weeks.
Plasma levels monitoringCorrelations between dosages and plasma levels of carbamazepine, as well as between plasma levels, and clinical efficacy or tolerability, are rather tenuous. However, monitoring of the plasma levels (therapeutic range in the treatment of epilepsy 4–12 mg/ L) may be useful in selected conditions, such as a dramatic increase in seizure frequency/ verification of patient compliance, during pregnancy, in suspected absorption disorders, in suspected toxicity due to polymedication.
  • Patients with a history of hepatic porphyrias.
  • Patients with a history of bone marrow depression.
  • Patients with atrioventricular block.
  • Patients with a history of haematological reactions to other drugs.
  • Patients with susceptibility to angle- closure glaucoma.
  • Patients with skin reactions.
  • Patients with cardiac disease.
  • Patients with absence and myoclonic seizures.
PharmacodynamicsCarbamazepine given in conventional tablets shows a mean peak concentration time during chronic treatment of about 4 hours, with an estimated oral bioavailability of 80-90%[21]. Carbamazepine is readily distributed in the body with an apparent volume of distribution (estimated on the presumption of a 100% oral bioavailability) of 0.8 2.0 /kg. Brain concentrations are about 1.21.4 times those in plasma and the breast milk/ total plasma level ratio is about 0.4 [22]. In plasma, CBZ binds to circulating proteins, mostly albumin and a1-acid glycoprotein. The bound fraction is about 70-80% and is constant in the interval of plasma concentrations normally observed in therapy[23].
Carbamazepine is mainly eliminated through hepatic metabolism by microsomal enzymes of the cytochrome P450 family. The main metabolites are epoxy-CBZ and 10.11-dihydro, 10,lldihydroxy carbarnazepine (CBZ-DIOL). In man, the hydroxylated derivatives are conjugated with glucuronic acid and excreted by the kidneys. Small amounts of unmodified CBZ are found in feces and in urine[24]. Quantitatively, the main urinary metabolite is CBZ-DIOL, which is, however, inactive. Carbamazepine-l0, 11-epoxideh as anticonvulsant potency similar to the parent drug, and has comparable efficacy in trigerninal neuralgia in man. After repeated dose, CBZ induces its own metabolism and its half-life is reduced by about 50%. Changing, for example, from 36 hours at the beginning of therapy to 21 hours after 3 weeks of treatment. Patients treated with other enzyme-inducing drugs may have a CBZ half-life as short as 5 16 hours. Children present a slightly higher CBZ clearance[21].
InteractionsWith AEDs
  • Plasma concentration of carbamazapine is increased by vigabatrin, whereas plasma concentration of the active metabolite carbamazepine 10,11- epoxide is increased by primidone and valproate (reduce carbamazepine dose to avoid increased risk of toxicity).
  • Plasma concentration of carbamazapine is reduced by cytochrome P450 3A4 inducers (including eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and, possibly, clonazepam).
  • Carbamazapine is a cytochrome P450 3A4 inducer and can decrease the plasma concentration of clobazam, clonazepam, ethosuximide, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate, valproate, and zonisamide.
  • Co- administration of levetiracetam has been reported to increase carbamazepine- induced toxicity; cross- sensitivity has been reported with oxcarbazepine and phenytoin.
With other drugs
  • Plasma concentration of carbamazapine is reduced by cytochrome P450 3A4 inducers aminophylline, cisplatin, doxorubicin, St John wort (Hypericum perforatum), isotretinoin, rifampicin, and theophylline (consider increasing the dose of carbamazapine).
  • Plasma concentration of carbamazapine is increased by cytochrome P450 3A4 inhibitors: acetazolamide, azoles (antifungals), cimetidine, ciprofloxacine, danazol, dextropropoxyphene, diltiazem, fluoxetine, fluvoxamine, isoniazid, loratadine, macrolide antibiotics, olanzapine, omeprazole, paroxetine, protease inhibitors (antivirals), trazodone, and verapamil. Plasma concentration of the active metabolite carbamazepine- 10,11- epoxide is increased by progabide, quetiapine, valnoctamide, and valpromide.
  • Carbamazepine is a cytochrome P450 3A4 inducer and can decrease the plasma concentration of albendazole, alprazolam, aprepitant, aripiprazole,atorvastatin, bromperidol, buprenorphine, bupropion, calcium channel blockers (e.g. felodipine), cerivastatin, ciclosporin, citalopram, clozapine, corticosteroids (e.g. prednisolone, dexamethasone), cyclophosphamide, digoxin, doxycycline, everolimus, haloperidol, hormonal contraceptives (oestrogens and progesterones), imatinib, itraconazole, ivabradine, lapatinib, levothyroxine, lovastatin, methadone, mianserin, olanzapine, oral anticoagulants (e.g. warfarin), paliperidone, paracetamol (acetaminophen), protease inhibitors (antivirals), quetiapine, rifabutin, risperidone, sertraline, simvastatin, tacrolimus, tadalafil, temsirolimus, theophylline, tramadol, trazodone, tricyclic antidepressants, voriconazole, and sirolimus.
With alcohol/food
  • Drinking alcohol may affect patients more than usual; eating grapefruit, or drinking grapefruit juice, may increase chance of experiencing adverse effects.
Special populationsHepatic impairment
  • Metabolism impaired in advanced liver disease.
Renal impairment
  • Use with caution.
  • Developmental disorders and malformations (including spina bifida), as well as other congenital anomalies (including craniofacial defects, such as cleft lip/ palate, cardiovascular malformations, hypospadias, and anomalies involving various body systems) have been reported in association with the use of carbamazepine during pregnancy. In women of childbearing age carbamazepine should, wherever possible, be prescribed as monotherapy, because the incidence of congenital abnormalities in the offspring of women treated with a combination of antiepileptic drugs is greater (especially if valproate is part of the polytherapy).
  • Pregnant women with epilepsy should be treated with minimum effective doses of carbamazepine and monitoring of plasma levels is recommended (aiming at the lower side of the therapeutic range, as there is evidence to suggest that the risk of malformation with carbamazepine may be dose- dependent).
  • Should a woman on carbamazepine decide to breastfeed, the infant should be monitored for possible adverse effects, as carbamazepine can be excreted in considerable amounts in breastmilk, which in combination with slow infantile elimination can result in plasma concentrations at which pharmacological effects occur. Since there have been reports of cholestatic hepatitis in neonates exposed to carbamazepine during antenatal and or during breastfeeding, breastfed infants of mothers treated with carbamazepine should be carefully observed for adverse hepatobiliary effects.
Mode of actionThe many effects of CBZ on the central nervous system include: the ability to bind to neuron membrane sodium channels when they are in the inactivated state, slowing the speed of reactivation and thus reducing the neuron's capacity of high frequency firing[25]; selective interaction with adenosine receptors and modification of the activity of second messengers like CAMP and cGMP and modification of various neurotransmitter systems[26]. An interesting aspect of CBZ action on the brain is the apparent selectivity for the limbic system, a feature that may provide an anatomical basis for both the psychotropic action of the drug and its efficacy in psychomotor epilepsies.
Carbamazepine is characterized by a good behavioural and cognitive profile in patients with epilepsy. Overall, adverse psychiatric effects (especially irritation, agitation, depression) are rarely reported in this patient population. Moderate cognitive problems affecting attention, memory, and language have occasionally been reported (especially at high doses).
Psychiatric useCarbamazepine was approved as a treatment for acute mania in 2004, decades after it was recognized as an effective alternative to lithium in the management of bipolar illness. Data from open- label trials suggest that carbamazepine is effective in the prophylaxis of bipolar disorder or acute mania, but may be less effective than valproate or lithium. However, carbamazepine has been suggested to be a better alternative for atypical manifestations of bipolar disorder, such as rapid cycling course, mood- incongruent delusions, or in the presence of other co- morbid psychiatric or neurological conditions. Carbamazepine may also be effective in unipolar depression, whereas its utility in schizophrenia is uncertain. In rarer cases, carbamazepine has been used to treat aggressive behaviour and to facilitate sedatives/ alcohol withdrawal, but there is no solid evidence to date to establish its efficacy in this domain. To summarize, evidence is strongest to support the mood stabilizing properties of carbamazepine.
Adverse reactions and precautionThe most common manifestations of acute CBZ toxicity at therapeutic dosages involve the central nervous and gastrointestinal systems (sedation. nystagmus, diplopia, ataxia, dizziness, nausea, vomiting, constipation, diarrhea) [27]. Dry mouth may occur as a consequence of some anticholinergic action of the drug. These symptoms respond to a dose reduction and, due to tolerance development, usually abate during treatment. Carbamazepine may induce involuntary movements such as myoclonic and choreoathetoid jerks, dystonia and asterixis[28]. Carbarnazepine has negative chmnotropic and dromotropic effects on cardiac conduction and may induce various types of bradyarrhythmia or even a complete atrioventricular block[28]. These dangerous complications are usually observed in elderly patients or patients with a preexisting impairment of cardiac conduction, are concentration-related, and require dose reduction or drug suspension.
During pregnancy, important modifications of CBZ kinetics may occur, requiring plasma concentration monitoring and, possibly, dosage adjustment[22]. CBZ enters breast milk (milk/plasma ratio of about 0.4)and a transfer of 1-4 mg/day of drug from mother to child takes place during nursing[22]. Concentrations in the breast-fed infant should not normally exceed 0.5 1.0 ug/ml, but somewhat higher concentrations, up to 4.7 ~ug /ml one case, have occasionally been reported[22]. These findings suggest that breast-feeding is not to be discouraged and that it should be discontinued only if the newborn shows signs of distress, such as blunted suck reflex.
  1. Takezaki H, Hanaoka M (1971). The use of carbamazepine (Tegretol) in the control of manic-depressive psychosis and other manic-depressive states. Clinical Psychiatry 13, 173–183.
  2. Okuma T, Kishimoto A, Inoue K, Matsumoto H, Ogura A, Matsushita T, Nakao T, Ogura C (1973). Anti-manic and prophylactic effects of carbamazepine (Tegretol) on manic-depressive psychosis: a preliminary report. Folia Psychiatrica et Neurologica 27, 283–297.
  3. Okuma T, Inanaga K, Otsuki S, Sarai K, Takahashi R, Hazama H, Mori A, Watanabe M (1979). Comparison of the antimanic efficacy of carbamazepine and chlorpromazine : a double-blind controlled study. Psychopharmacology 66, 211–217.
  4. Brambilla P, Barale F, Soares JC (2001). Perspectives on the use of anticonvulsants in the treatment of bipolar disorder. International Journal of Neuropsychopharmacology 4, 421–446.
  5. Post RM, Ketter TA, Denicoff K (1996a). The place of anticonvulsant therapy in bipolar illness. Psychopharmacology 128, 115–129.
  6. Loiseau. P, B. Duche: Carbamazepine. Clinical use. In: Levy, R H., E E. Dreifus. R H. Mattson, B. S. Me1drum.J. K. Penly (eds.): Antiepileptic drugs. Raven Press. New York 7989 p. 553-554
  7. Michels. R. P. M. Marzuk: Progress in psychiatry. N. Engl. J. Med. 329 (1993) 628 -638
  8. Okuma, 1, I. Yamashita, R Takahashi, H. Itoh, S. Otsuki. S. Watanabe. S. Sarai. H. Hazama. K. Inanaga: Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by doubleblind controlled study. Pharmacopsychiatry 23 (1990) 143-150
  9. Small, J. G., M. H. Klapper, V. Milstein.].]. Kellmans, M.J. Miller.]. D. Marhenke, I. E Small: Carbamazepine compared with lithium in the treatment of mania. Arch. Gen. Psych. 48 (1991) 915-921
  10. Post, R M., 1 A. Ketter, P. J. Pauaglia. M. S. George, L. MamngelI, K. Denicoff: New developments in the use of anticonvulsants as mood stabilizers. Neuropsychobiology 27 (1993) 132-137
  11. Maj, M., R Pimzzi. D. Kemali: Long-term outcome of lithium prophylaxis in patients initially classified as complete responders. Psychopharmacology 98 (1989) 535-538
  12. Evans, R W., C. T. Gualtieri: Carbamazepine: a neurological and psychiatric profile. Clin. Neuropharrnacol. 8 (1985) 221 -241
  13. Cullen. M., P. Mitchell, H. Brodaty, I? Royce, G. Parker, I. Hickie. K Wilhelm: Carbamazepine for treatment-resistant melancholia. J. Clin. Psychiatry 52 (1991) 472-476
  14. Stuppaeck, C. H., C H. Barnas, K. Hackenberg, C. H. Miller. W. W. Neischhacker: Carbamazepine monotherapy in the treatment of alcohol withdrawal. Int. Clin. Psychopharmacol. 5 (1990)2 73 -278
  15. Gleason, R P, L, S. Schneider: Carbamazepine treatment of agitation in Alzheimer's outpatients refractory to neuroleptics. J. Clin. Psychiatry 51 (1990) 115118
  16. Chouinard G.. S. Sultan: Treatment of supersensitivity psychosis with antiepileptic drugs: report of a series of 43 cases. Psychopharmacol. Bull. 26 (1990) 337-341
  17. Stuppaeck, C. H., C H. Barnas, K. Hackenberg, C. H. Miller. W. W. Neischhacker: Carbamazepine monotherapy in the treatment of alcohol withdrawal. Int. Clin. Psychopharmacol. 5 (1990)2 73 -278
  18. Garcia. B.. E. Zaborras, V. Arease. G. Obeso, I. jimena, P. DeJuana, T. Bermejo: Interaction between isoniazid and carbamazepine potentiated by cimetidine. DlCP 26 (1992) 841
  19. Keck, F. E. jr, S. L McElroy. K. C. Tugrul. J. A. Bennett,. M. R. Smith: Antiepileptic drugs for the treatment of panic disorder. Neurobiology 27 (1993) 150-153
  20. Uhde, Z W.. M. B. Stein, R. M. Post: Lack of efficacy of carbamazepine in the treatment of panic disorder. Am. J. Psychiatry 145 (1988) 1104-1109
  21. Morselli, P. L: Carbamazepine. Absorption, distribution and excretion. In: Levy, R H., E E Dreifuss, R H. Mattson, B. S. Me1drum.J. K. Penry (eds.): Antiepileptic Drugs. Raven Press, New York 1989 p. 473-490
  22. Nau. H., W. Ku hnz, H. J. Egger. D. Rating, H. Helge: Anticonvulsants during pregnancy and lactation. Transplacental, maternal and neonatal pharmacokinetics. Clin. Pharmacokinet. 7 (1982) 508543
  23. Contin, M., R Riva, E Albani. E. Perucca. G. Lamonfanara, A. Banrui: a1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine 10,ll-epoxide in children with epilepsy. Eur. J. Clin. Pharmacol. 29 (1985) 211 -214
  24. Faigle.J. W., K. E Feldmann: Carbamazepine Biotransformation In: Levy. R. H.. E E. Dreifuss, R H. Mattson, B. 5. Me1dnrm.j. K. Penry (eds.): Antiepileptic Drugs. Raven Press, New York 1989, p.491 – 504
  25. Macdonald, R. L: Carbamazepine. Mechanisms of action. In: Levy, R H.. E. Dreifiss, R H. Mattson. B. S. Meldrum,]. K. Penry (eds.): Antiepileptic drugs. Raven Press. New York 1989, p. 447-471
  26. Motohashi. N.: Gaba receptor alterations after chronic lithium administration. Comparison with carbamazepine and sodium valproate. Prog. Neuro-psychophannacol. Biol. Psychiatry 16 (1992) 571 – 579
  27. Askrnark, H.. B. E. Wiholm: Epidemiology of adverse reactions to carbamazepine as seen in a spontaneous reporting system. Acta Neurol. Scand. 81 (1990) 131 -140
  28. Gram L, P K. jensen: Carbarnazepine Toxicity. In: Levy. R. H., R. Mattson, B. Meldrum, J. K Pen% E E. Dreifuss (eds.): Antiepileptic Drugs. Raven Press. New York 1989, p. 555-565
DescriptionCarbamazepine 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.
Chemical PropertiesWhite Solid
OriginatorTegretol,Geigy,W. Germany,1964
Usesanalgesic, anticonvulsant
UsesUsed in treatment of pain associated with trigeminal neuralgia. Anticonvulsant
UsesCarbamazepine (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).
DefinitionChEBI: A dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant.
Manufacturing Process19.3 parts of iminostilbene are dispersed in 100 parts by volume of toluene. Phosgene is then introduced whereupon the temperature of the reaction mixture rises to 70°C. While boiling under reflux, further phosgene is introduced until all the iminostilbene has dissolved and the hydrogen chloride development is complete. The reaction mixture is then cooled and the 5- chlorocarbonyl iminostilbene which has crystallized out is filtered off under suction. It melts at 168° to 169°C.
12.8 parts of 5-chlorocarbonyl iminostilbene are dispersed in 128 parts by volume of absolute ethanol and ammonia gas is introduced for three hours into this mixture while stirring at boiling temperature. The reaction is complete after this time; the reaction mixture is cooled and the crystals which precipitate are filtered off under suction. The ammonium chloride is washed from the crystals with water and the residue is recrystallized first from absolute ethanol and then from benzene. 5-carbamyl iminostilbene is obtained which melts at 204° to 206°C.
Brand nameCarbatrol (Shire); Epitol (Teva); Equetro (Shire); Tegretol (Novartis); Teril (Taro).
Therapeutic FunctionAnalgesic, Anticonvulsant
Biological FunctionsCarbamazepine 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.
Biochem/physiol ActionsAnticonvulsant; ligand for the GABAA receptor benzodiazepine modulatory site. Sodium channel inhibitor.
Mechanism of actionIn 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.
PharmacokineticsFollowing the administration of an oral dose, CBZ is slowly absorbed, with the attainment of peak concentration from immediate-release tablets in 4 to 5 hours and from extended-release tablets in 3 to 12 hours. The normal half-life averages between 12 and 17 hours; however, because of autoinduction, the half-life may range from 8 to 29 hours. The half-life for CBZ-10,11-epoxide is 5 to 8 hours. Therapeutic plasma concentrations range from 4 to 12 μg/mL (in adults) and may require a month to achieve a stable therapeutic concentration for the desired antiseizure effect because of induction of hepatic metabolizing enzymes.
CBZ is principally metabolized by CYP3A4 its 10,11-epoxide, with CYP2C8 and CYP1A2 having minor roles. CBZ epoxide is hydrolyzed to inactive 10,11-dihydroxy CBZ by epoxide hydrolase. CBZ epoxide is active and appears to be more toxic than CBZ. However, CBZ not only induces CYP3A4 activity but also its own metabolism (an autoinducer) as well as UGT and the increased formation of glucuronide metabolites. Like phenytoin, CBZ has been associated with a number of toxic effects, including a drug-induced hypersensitivity syndrome. Although phenytoin-induced hypersensitivity reactions are relatively rare events, they can be potentially life-threatening. Although the mechanism by which CBZ induces hypersensitivity reactions has not been well characterized, recent studies have suggested that the immune reaction may be caused, at least in part, by its metabolism into chemically reactive metabolites, which may be the critical step in the formation of protein adducts and subsequent immune responses.
Clinical UseCarbamazepine 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.
Side effectsLike most of the agents that block sodium channels, side effects associated with carbamazepine administration involve the central nervous system (CNS). Drowsiness is the most common side effect, followed by nausea, headache, dizziness, incoordination, vertigo, and diplopia.These effects occur particularly when the drug is first taken, but tolerance often develops over a few weeks. There appears to be little risk of cognitive impairment with carbamazepine.
Carbamazepine causes a variety of rashes and other allergic reactions including fever, hepatosplenomegaly, and lymphadenopathy, but the incidence of serious hypersensitivity reactions is rare. Systemic lupus erythematosus can occur, but discontinuation of the drug leads to eventual disappearance of the symptoms. Idiosyncratic hematological reactions to carbamazepine may occur, but serious blood dyscrasias are rare. Carbamazepine has been shown to exacerbate or precipitate seizures in some patients, particularly those exhibiting generalized atypical absences.
While the number of side effects may be fairly large, most are not serious and can be managed. Severe adverse reactions occur less commonly than with phenytoin and similar drugs. The overall incidence of toxicity seems to be fairly low at usual therapeutic doses. Most of the drug interactions with carbamazepine are related to its effects on microsomal drug metabolism. Carbamazepine can induce its own metabolism (autoinduction) after prolonged administration, decreasing its clearance rate, half-life, and serum concentrations. The possibility of autoinduction requires the clinician to reevaluate the patient’s blood levels after a month of carbamazepine therapy. The autoinduction phenomenon is over in about a month.
Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine; the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug–drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and troleandomycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop; this is readily reversible if either the antibiotic or carbamazepine is discontinued.
Chemical SynthesisCarbamazepine, 5H-dibenz[b,f]azepine-5-carboxamide (9.5.2), is synthesized by reacting 5H-dibenz[b,f]azepine and phosgene, which forms 5-chlorcarboxy- 5H-dibenz-[b,f]azepine (9.5.1), and its subsequent reaction with ammonia to give the desired carbamazepine (9.5.2) [16]. An alternative method of synthesis is the direct reaction of 5H-dibenz[b,f]azepine with potassium cyanate [17].

Environmental FateCarbamazepine 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.
Toxicity evaluationEnvironmental exposure occurs via direct release into water or via vaporization into the air. It is susceptible to photolysis and is thought to have a half-life of roughly 63 days in lake water in vitro. However, when dissolved and exposed to direct photolysis, it has a half-life of approximately 1 day.
Carbamazepine Preparation Products And Raw materials
Raw materials2-Nitrotoluene-->Iminostilbene-->2,2'-ETHYLENEDIANILINE-->Ammonia-->PHOSGENE
Preparation Products5H-Dibenz[b,f]azepine-10,11-dione
Tag:Carbamazepine(298-46-4) Related Product Information