View source for Sultiame

{{Short description|Chemical compound}}
{{Infobox drug
| Verifiedfields = changed
| verifiedrevid = 470474738
| IUPAC_name = 4-(1,1-dioxothiazinan-2-yl)benzenesulfonamide
| image = Sultiame.svg
| AAN = Sulthiame
| USAN = sulthiame
<!--Clinical data-->
| tradename =  Ospolot
| Drugs.com = {{drugs.com|international|sultiame}}
| pregnancy_AU = D
| legal_AU = S4
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
| bioavailability = 100% (oral)
| protein_bound = 29%
| metabolism = [[Liver|Hepatic]] secretion
| elimination_half-life = 24 hours
| excretion = Fecal (10%) and [[Kidney|renal]] (90%)
<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 61-56-3
| ATC_prefix = N03
| ATC_suffix = AX03
| PubChem = 5356
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB08329
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5163
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = I00Q766CZ2
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01787
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 328560
<!--Chemical data-->
| C=10 | H=14 | N=2 | O=4 | S=2
| smiles = O=S2(=O)N(c1ccc(cc1)S(=O)(=O)N)CCCC2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H14N2O4S2/c11-18(15,16)10-5-3-9(4-6-10)12-7-1-2-8-17(12,13)14/h3-6H,1-2,7-8H2,(H2,11,15,16)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HMHVCUVYZFYAJI-UHFFFAOYSA-N
}}
'''Sultiame''' (or '''sulthiame''') is a [[sulfonamide (medicine)|sulfonamide]] and [[Enzyme inhibitor|inhibitor]] of the [[enzyme]] [[carbonic anhydrase inhibitor|carbonic anhydrase]]. It is used as an [[anticonvulsant]] and in recent studies showed promise in reducing sleep disordered breathing and other symptoms of obstructive sleep apnea (OSA).
==History==
Sultiame was first synthesised in the laboratories of [[Bayer]] AG in the mid-1950s and eventually launched as '''Ospolot''' in [[Europe]] and other markets the early 1960s. It never became a registered drug in the United States. The brand was transferred to Desitin GmbH in 1993 and is sold in several European countries, in Israel, Japan, and Australia.
Sultiame became established as a second-line drug for treatment of [[Focal seizures|partial]] epilepsy in the 1960s and 1970s and was often used in combination with the established anticonvulsant [[phenytoin]]. [[temporal lobe epilepsy|Temporal lobe seizures]] appeared particularly responsive to sultiame. Doubts subsequently arose as to whether sultiame has [[intrinsic]] anticonvulsant properties. After discovering sultiame's ability to raise the blood levels of [[phenytoin]],<ref name = "Hansen_1968">{{cite journal | vauthors = Hansen JM, Kristensen M, Skovsted L | title = Sulthiame (Ospolot) as inhibitor of diphenylhydatoin metabolism | journal = Epilepsia | volume = 9 | issue = 1 | pages = 17–22 | date = March 1968 | pmid = 4386877 | doi = 10.1111/j.1528-1157.1968.tb04954.x | s2cid = 20168357 }}</ref> it was assumed that sultiame would only act in combination with phenytoin. This finding, together with the equivocal results of a study in the US,<ref name = "Hansen_1968" /> resulted in a quick decline of sultiame's use. It was only in 1988, that the [[Germany|German]] child neurologist [[Hermann Doose]] discovered its specific effects in [[benign focal epilepsies of childhood]].<ref>{{cite journal | vauthors = Doose H, Baier WK, Ernst JP, Tuxhorn I, Völzke E | title = Benign partial epilepsy--treatment with sulthiame | journal = Developmental Medicine and Child Neurology | volume = 30 | issue = 5 | pages = 683–4 | date = October 1988 | pmid = 2906619 | doi = 10.1111/j.1469-8749.1988.tb04809.x | s2cid = 37726714 }}</ref> Today,  sulthiame is the drug of choice for benign focal epilepsies of childhood (such as [[benign rolandic epilepsy]]) in the [[German language|German]]-speaking countries and Israel.<ref>{{cite journal | vauthors = Debus OM, Kurlemann G | title = Sulthiame in the primary therapy of West syndrome: a randomized double-blind placebo-controlled add-on trial on baseline pyridoxine medication | journal = Epilepsia | volume = 45 | issue = 2 | pages = 103–8 | date = February 2004 | pmid = 14738417 | doi = 10.1111/j.0013-9580.2004.19003.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Koepp MJ, Patsalos PN, Sander JW | title = Sulthiame in adults with refractory epilepsy and learning disability: an open trial | journal = Epilepsy Research | volume = 50 | issue = 3 | pages = 277–82 | date = August 2002 | pmid = 12200218 | doi = 10.1016/s0920-1211(02)00054-2 | s2cid = 13220334 }}</ref>
==Indications==
Historically, sultiame has been used to treat [[Focal seizures|partial]] seizures. In Australia, it is currently registered for behavioural disorders associated with [[epilepsy]]; [[Attention-deficit hyperactivity disorder|hyperkinetic]] behaviour; temporal lobe epilepsy; [[Myoclonus|myoclonic]] [[seizure]]s; [[grand mal]] attacks; and [[Jacksonian seizure]]s.<ref>[http://www.pharmalab.com.au/resources/5/Ospolot%20PI%20TAB002%20TAB003%20Version0804.pdf Pharmalab Pty Ltd. ''Product Information Ospolot (Sulthiame)''.]</ref> In contrast to other sulfonamide drugs, sultiame is devoid of [[antibacterial]] activity.
Latest research is evaluating sultiamine for sleep apnea with early positive results.<ref>[https://www.medscape.com/viewarticle/oral-epilepsy-drug-eases-symptoms-osa-2024a1000h8l Medscape ''Oral Epilepsy Drug Eases Symptoms of OSA''.]</ref>
==Adverse effects==
{{unreferenced section|date=October 2015}}
The more common adverse effects are [[ataxia]], [[paraesthesia]] of face and limbs, [[hyperpnoea]], [[dyspnoea]], and [[Anorexia nervosa|anorexia]]. Less common adverse effects include giddiness, rash, [[Stevens–Johnson syndrome]], [[nausea]], weight loss, [[leukopenia]], headache, depression, drooling, increased pain, [[insomnia]], [[status epilepticus]]. Disturbances in [[calcium]] and [[vitamin D]] [[metabolism]] have been occasionally reported after long-term use.
== Interactions ==
Sultiame taken together with [[primidone]] may lead to severe side-effects, including psychotic reactions. The addition of sulthiame to phenytoin therapy has shown to be followed by a rise in the serum levels of phenytoin. Sultiame may also lead to a rise of [[phenobarbitone]] blood levels. [[Alcohol (drug)|Alcohol]] must not be consumed during treatment.
==Overdose==
[[Vomiting]], [[hypotension]], headache, [[vertigo (medical)|vertigo]], [[ataxia]], metabolic [[acidosis]] with [[hyperpnoea]] and [[catatonic]] state may occur. There is no specific [[antidote]]. It is not known whether [[Kidney dialysis|dialysis]] may help in case of overdose.
==Synthesis==
[[File:Sultiame synthesis.png|thumb|center|700px|Sultiame synthesis: B. Helferich and R. Behnisch, {{US Patent|2,916,489}}  (1959).]]
[[Sulfanilamide]] can be reacted with ω-chlorobutylsulfonyl chloride and aqueous sodium carbonate to form the presumed intermediate (middle), which spontaneously cyclizes to give the drug.
== References ==
{{reflist|1}}
{{Anticonvulsants}}
[[Category:Anticonvulsants]]
[[Category:Sulfonamides]]
[[Category:Carbonic anhydrase inhibitors]]
[[Category:Thiazines]]
[[Category:Sultams]]
[[Category:Sulfur–nitrogen compounds]]