Article: Carbamazepine

Carbamazepine
Systematic (IUPAC) name
5H-dibenz[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. weight	236.269 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	76%
Metabolism	hepatic CYP3A4 to active epoxide form
Half life	25-65 hours
Excretion	2-3% excreted unchanged in urine
Therapeutic considerations
Pregnancy cat.	D
Legal status	PoM (UK)
Routes	oral

Carbamazepine (sold under the brand-names Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Tegretol, Telesmin, Timonil) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat schizophrenia and trigeminal neuralgia.

Mechanisms

Carbamazepine and its derivatives' mechanism of action is relatively well understood. Voltage gated sodium channels are the molecular pores that allow brain cells (neurons) to generate action potentials, the electrical event that allows 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 sodium channels are available to open, making brain cells less excitable.

Side effects

Carbamazepine renders birth control pills ineffective because it lowers the level of estrogen produced by them.

Common side effects include drowsiness, motor-coordination impairment and/or upset stomach. Taken every twelve hours, the Tegretol XR or Carbatrol preparations can greatly decrease alcohol tolerance.

Less common side effects include, cardiac arrythmias, blurry or double vision and/or the temporary or mild loss of blood cells or platelets. In rare cases the latter can be life-threatening if unnoticed, so frequent blood tests are required during the first few months' use, followed by three or four tests per year. There are also reports of a bizarre auditory side effect, whereby patients perceive musical notes about a semitone lower than their actual pitch (so middle C would be heard as the note B3 just below it, etc).

Oxcarbazepine, a derivative of carbamazepine, has fewer and less serious side effects.

Carbamazepine can cause SIADH (syndrome of inappropriate antidiuretic hormone), since it both increases the release and potentiates the action of ADH (vasopressin).

Carbamazepine greatly reduces serum concentrations of simvastatin and simvastatin acid ^{[ 1 ]}.

History

Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953. Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered.

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.