Carbamazepine
Systematic (IUPAC) name
(Z)-5H-dibenzo[b,f]azepine-5-carboxamide
Identifiers
CAS number	298-46-4 85756-57-6 (dihydrate)
ATC code	N03AF01
PubChem	2554
DrugBank	APRD00337
Chemical data
Formula	C15H12N2O
Mol. mass	236.269 g/mol
Pharmacokinetic data
Bioavailability	80%
Protein binding	76%
Metabolism	Hepatic—by CYP3A4, to active epoxide form (carbamazepine-10,11 epoxide)
Half life	25–65 hours
Excretion	2–3% excreted unchanged in urine
Therapeutic considerations
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Routes	Oral

Carbamazepine ("CBZ") is an benzodiazepiene and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat ADD, ADHD, schizophrenia and trigeminal neuralgia. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by rapid and unstable mood shifts. ... For other uses, see Bipolar. ... Attention-Deficit Hyperactivity Disorder (ADHD), is a neurobehavioural developmental disorder[1] [2] [3] affecting about 3-5% of the worlds population under the age of 19[4]. It typically presents itself during childhood, and is characterized by a persistent pattern of inattention and/or hyperactivity, as well as forgetfulness... DISCLAIMER Please remember that Wikipedia is offered for informational use only. ... Trigeminal neuralgia, or Tic Douloureux, is a neuropathic disorder of the trigeminal nerve that causes episodes of intense pain in the eyes, lips, nose, scalp, forehead, and jaw. ...

Trade names

Carbamazepine has been sold under the names Tegretol, Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Telesmin,Teril, Timonil, Trimonil, Epimaz, and Degranol (in South Africa)^[1].

History

Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953.^[2] Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered. Novartis headquarters in Basel Suffern, New York: the sole Novartis pharmaceutical production facility in the United States. ... For other uses, see Basel (disambiguation). ...

Carbamazepine was first marketed as a drug to treat trigeminal neuralgia in 1962. It has been used as an anticonvulsant in the UK since 1965, but only approved in the U.S. since 1974. Trigeminal neuralgia, or Tic Douloureux, is a neuropathic disorder of the trigeminal nerve that causes episodes of intense pain in the eyes, lips, nose, scalp, forehead, and jaw. ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...

In 1971, Drs. Takezaki and Hanaoka first used carbmazepine to control mania in patients refractory to antipsychotics (lithium was not available in Japan at that time). Dr. Okuma, working independently, did the same thing with success. As they were also epileptologists, they had some familiarity with the anti-aggression effects of this drug. Carbamazepine would be studied for bipolar disorder throughout the 1970s.^[3]

Adverse effects

Carbamazepine is known to render many hormonal contraception products ineffective, due to its action as a cytochrome P450 enzyme inducer, which is the system that metabolizes many oral contraceptives. Carbamazepine causes more cytochrome P450 enzyme to be produced, which hastens removal of the contraceptive from the blood plasma although the clinical significance of this effect is debatable. Hormonal contraception refers to birth control methods that act on the hormonal system. ...

Common side effects include drowsiness, motor coordination impairment and/or upset stomach. Carbamazepine preparations may also greatly decrease a person's alcohol tolerance. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted, negative consequences associated with the use of given medications. ... Explain the dystonias connected with motor coordination. ...

Less common side effects include cardiac arrhythmias, blurry or double vision and/or the temporary loss of blood cells or platelets. With normal use, small reductions in white cell count and serum sodium are common, however, in rare cases, the loss of platelets may become life-threatening. This occurs commonly enough that a doctor may recommend frequent blood tests during the first few months of use, followed by three to four tests per year for established patients. In the UK, testing is generally performed much less frequently for long-term carbamazepine patients -typically once per year. Additionally, carbamazepine may exacerbate preexisting cases of hypothyroidism, so yearly thyroid function tests are advisable for persons taking the drug. In psychology, visual perception is the ability to interpret visible light information reaching the eyes which is then made available for planning and action. ... A blood cell is any cell of any type normally found in blood. ... A 250 ml bag of newly collected platelets. ...

There are also reports of an auditory side effect for carbamazepine use, whereby patients perceive sounds about a semitone lower than their actual pitch. Thus, middle C would be heard as the note B3 just below it, etc. This unusual side-effect is usually not noticed by most people, and quickly disappears after the person stops taking carbamazepine. A semitone (also known in the USA as a half step) is a musical interval. ... In Western music, the expression middle C refers to the note C or Do located exactly between the two staves of the grand staff, quoted as C4 in note-octave notation (also known as scientific pitch notation). ... This article or section may be confusing for some readers, and should be edited to be clearer or more simplified. ...

Oxcarbazepine, a derivative of carbamazepine, reportedly has fewer and less serious side effects. Oxcarbazepine (marketed as Trileptal® by Novartis or Trexapin by Taro) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. ...

Carbamazepine may cause SIADH (syndrome of inappropriate anti-diuretic hormone), since it both increases the release and potentiates the action of ADH (vasopressin). Arginine vasopressin (AVP), also known as argipressin or antidiuretic hormone (ADH), is a human hormone that is released when the body is low on water; it causes the kidneys to conserve water, but not salt, by concentrating the urine and reducing urine volume. ...

Carbamazepine may aggravate juvenile myoclonic epilepsy, so it is important to mention any history of jerking, especially in the morning, before starting to take this drug. Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a fairly common form of idiopathic generalized epilepsy, representing 5-10% of all epilepsies. ...

Pregnant women taking carbamazepine put their fetuses at increased risk for teratogenic effects. As a result, they should be given folic acid supplementation and undergo prenatal ultrasonography for diagnosis. Folic acid and folate (the anion form) are forms of the water-soluble Vitamin B9. ...

In addition, carbamazepine has been linked to serious adverse cognitive anomalies, including EEG slowing^[4] and cell apoptosis.^[5]

The FDA informed healthcare professionals that dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. ^[6]

Mechanism of Action

The mechanism of action of carbamazepine and its derivatives is relatively well understood. Voltage-gated sodium channels are the molecular pores that allow brain cells (neurons) to generate action potentials, the electrical events that allow neurons to communicate over long distances. After the sodium channels open, to start the action potential, they inactivate, essentially closing the channel. Carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to open, making brain cells less excitable. Sodium channels are integral membrane proteins that exist in a cells plasma membrane and regulate the flow of sodium (Na+) ions into it. ... This article is about cells in the nervous system. ... A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. ... This article is about cells in the nervous system. ...

When Carbamazepine is used in the treatment of Bipolar disorder the mode of action is inhibition of Glycogen synthase kinase-3. (Per Dr Martin Department of Pharmacology ATSU)

Interactions

Valproic acid and valnoctamide both interact with carbamazepine, as they inhibit microsomal epoxide hydrolase (mEH), the enzyme responsible for the breakdown of carbamazepine-10,11 epoxide into inactive metabolites.^[7] By inhibiting mEH, valproic acid and valnoctamide cause a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion. Valproic acid (VPA) is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder. ... Valnoctamide has been used in France as a tranquilizer and muscle relaxant since 1964[3] and as an anticonvulsant since starting in 1969 in Portugal. ... In general, the epoxide hydrolase system functions in detoxication during drug metabolism. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ...

Carbamazepine interacts with multiple drugs and caution should be used in combining other medicines with it. Lower levels of carbamazepine are seen when administrated with phenobarbital, phenytoin (Dilantin), or primidone (Mysoline). Warfarin (Coumadin), phenytoin (Dilantin), theophylline, and valproic acid (Depakote, Depakote ER, Depakene, Depacon) are more rapidly metabolized with carbamazepine, while carbamazepine levels are elevated when taken with erythromycin, cimetidine (Tagamet), propoxyphene (Darvon), and calcium channel blockers. Carbamazepine also increases the metabolism (destruction) of the hormones in birth control pills and can reduce the effectiveness of birth control pills. Unexpected pregnancies have occurred in patients taking both carbamazepine and birth control pills

Carbamazepine,as CYP 450 inducer, may increase clearance of many drugs, decreasing their blood levels.

See also

• Oxcarbazepine

Oxcarbazepine (marketed as Trileptal® by Novartis or Trexapin by Taro) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. ...

References

1. ^ Degranol® Tablets
2. ^ Schindler W, Häfliger F (1954). "Über Derivate des Iminodibenzyls". Helvetica Chimica Acta 37 (2): 472–83.. doi:10.1002/hlca.19540370211. 
3. ^ Okuma T, Kishimoto A (February 1998). "A history of investigation on the mood stabilizing effect of carbamazepine in Japan". Psychiatry Clin. Neurosci. 52 (1): 3–12. PMID 9682927. 
4. ^ Salinsky MC, Binder LM, Oken BS, Storzbach D, Aron CR, Dodrill CB (2002). "Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers". Epilepsia 43 (5): 482–90. doi:10.1046/j.1528-1157.2002.22501.x. PMID 12027908. 
5. ^ Gao XM, Margolis RL, Leeds P, Hough C, Post RM, Chuang DM (1995). "Carbamazepine induction of apoptosis in cultured cerebellar neurons: effects of N-methyl-D-aspartate, aurintricarboxylic acid and cycloheximide". Brain Res. 703 (1-2): 63–71. PMID 8719616. 
6. ^ MedWatch (December 12, 2007). Carbamazepine. 2007 Safety Alerts for Drugs, Biologics, Medical Devices, and Dietary Supplements. FDA.
7. ^ Gonzalez, Frank J.; Robert H. Tukey (2006). "Drug Metabolism", in Laurence Brunton, John Lazo, Keith Parker (eds.): Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11^th ed., New York: McGraw-Hill, p. 79. ISBN 978-0071422802. 

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External links

• Carbatrol website
• Equetro website
• TA warning
• Carbamazepine overview from PsychEducation.org
• U.S. Patent 2,948,718, August 1960