ethosuximide ethosuximide ethosuximide, sold under the brand name zarontin among others, is a medication used to treat absence seizures. it may be used by itself or with other antiseizure medications such as valproic acid. ethosuximide is taken by mouth. ethosuximideclinical datatrade nameszarontin, othersahfs/drugs.commonographmedlineplusa682327license data us dailymed: ethosuximide pregnancycategory au: d routes ofadministrationby mouth (capsules, solution)atc coden03ad01 (who) legal statuslegal status us: ℞-only eu: rx-only in general: ℞ (prescription only) pharmacokinetic databioavailability93%metabolismliver (cyp3a4, cyp2e1)elimination half-life53 hoursexcretionkidney (20%)identifiers iupac name (rs)-3-ethyl-3-methyl-pyrrolidine-2,5-dione cas number77-67-8 ypubchem cid3291iuphar/bps7182drugbankdb00593 ychemspider3175 yunii5seh9x1d1dkeggd00539 ychebichebi:4887 ychemblchembl696 ycomptox dashboard (epa)dtxsid7023019 echa infocard100.000.954 chemical and physical dataformulac7h11no2molar mass141.170 g·mol−13d model (jsmol)interactive imagechiralityracemic mixturemelting point64 to 65 °c (147 to 149 °f) smiles o=c1nc(=o)cc1(c)cc inchi inchi=1s/c7h11no2/c1-3-7(2)4-5(9)8-6(7)10/h3-4h2,1-2h3,(h,8,9,10) ykey:hapovyfovvwlrs-uhfffaoysa-n y (verify) ethosuximide is usually well tolerated. common side effects include loss of appetite, abdominal pain, diarrhea, and feeling tired. serious side effects include suicidal thoughts, low blood cell levels, and lupus erythematosus. it is unclear if it has adverse effects on the fetus during pregnancy. ethosuximide is in the succinimide family of medications. its mechanism of action is thought to be due to antagonism of the postsynaptic t-type voltage-gated calcium channel. ethosuximide was approved for medical use in the united states in 1960. it is on the world health organization's list of essential medicines. ethosuximide is available as a generic medication. as of 2019 its availability was limited in many countries with concerns of price fixing in the united states. medical uses it is approved for absence seizures. ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence drug, valproic acid. adverse effects as with other anticonvulsants, ethosuximide carries a warning about use during pregnancy. although a causal relationship with birth defects has not be established, the potential for harm to the baby is weighed against the known harm caused by a mother having even minor seizures. common drowsiness mental confusion insomnia headache ataxia rare paranoid psychosis increased libido exacerbation of depression gastrointestinal dyspepsia vomiting nausea cramps constipation diarrhea stomach pain loss of appetite weight loss gum enlargement swelling of tongue abnormal liver function genitourinary microscopic hematuria vaginal bleeding blood the following can occur with or without bone marrow loss: pancytopenia agranulocytosis leukopenia eosinophilia skin urticaria systemic lupus erythematosus stevens–johnson syndrome hirsutism pruritic erythematous rashes eyes myopia drug interactions valproates can either decrease or increase the levels of ethosuximide; however, combinations of valproates and ethosuximide had a greater protective index than either drug alone. it may elevate serum phenytoin levels. mechanism of action the mechanism by which ethosuximide affects neuronal excitability includes block of t-type calcium channels, and may include effects of the drug on other classes of ion channel. the primary finding that ethosuximide is a t-type calcium channel blocker gained widespread support, but initial attempts to replicate the finding were inconsistent. subsequent experiments on recombinant t-type channels in cell lines demonstrated conclusively that ethosuximide blocks all t-type calcium channel isoforms. significant t-type calcium channel density occurs in dendrites of neurons, and recordings from reduced preparations that strip away this dendritic source of t-type calcium channels may have contributed to reports of ethosuximide ineffectiveness. in march 1989, coulter, huguenard and prince showed that ethosuximide and dimethadione, both effective anti-absence agents, reduced low-threshold ca2+ currents in t-type calcium channels in freshly removed thalamic neurons. in june of that same year, they also found the mechanism of this reduction to be voltage-dependent, using acutely dissociated neurons of rats and guinea pigs; it was also noted that valproic acid, which is also used in absence seizures, did not do that. the next year, they showed that anticonvulsant succinimides did this and that the pro-convulsant ones did not. the first part was supported by kostyuk et al. in 1992, who reported a substantial reduction in current in dorsal root ganglia at concentrations ranging from 7 μmol/l to 1 mmol/l. that same year, however, herrington and lingle found no such effect at concentrations of up to 2.5 mmol/l. the year after, a study conducted on human neocortical cells removed during surgery for intractable epilepsy, the first to use human tissue, found that ethosuximide had no effect on ca2+ currents at the concentrations typically needed for a therapeutic effect. in 1998, slobodan m. todorovic and christopher j. lingle of washington university reported a 100% block of t-type current in dorsal root ganglia at 23.7 ± 0.5 mmol/l, far higher than kostyuk reported. that same year, leresche et al. reported that ethosuximide had no effect on t-type currents, but did decrease noninactivating na+ current by 60% and the ca2+-activated k+ currents by 39.1 ± 6.4% in rat and cat thalamocortical cells. it was concluded that the decrease in na+ current is responsible for the anti-absence properties. in the introduction of a paper published in 2001, dr. juan carlos gomora and colleagues at the university of virginia in charlottesville pointed out that past studies were often done in isolated neurons that had lost most of their t-type channels. using cloned α1g, α1h, and α1i t-type calcium channels, gomora's team found that ethosuximide blocked the channels with an ic50 of 12 ± 2 mmol/l and that of n-desmethylmethsuximide (the active metabolite of mesuximide) is 1.95 ± 0.19 mmol/l for α1g, 1.82 ± 0.16 mmol/l for α1i, and 3.0 ± 0.3 mmol/l for α1h. it was suggested that the blockade of open channels is facilitated by ethosuximide's physically plugging the channels when current flows inward. stereochemistry ethosuximide is a chiral drug with a stereocenter. therapeutically, the racemate, the 1: 1 mixture of ( s ) and ( r ) - isomers used. enantiomers of ethosuximide cas-nummer: 39122-20-8 cas-nummer: 39122-19-5 society and culture cost as of 2019 there were concerns in the united states that the price of ethosuximide was inflated by manufacturers. availability availability of ethosuximide is limited in many countries. it was marketed under the trade names emeside and zarontin. however, both capsule preparations were discontinued from production, leaving only generic preparations available. emeside capsules were discontinued by their manufacturer, laboratories for applied biology, in 2005. similarly, zarontin capsules were discontinued by pfizer in 2007. syrup preparations of both brands remained available.