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{{drugbox
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 470474738
| IUPAC_name = 4-(1,1-dioxothiazinan-2-yl)benzenesulfonamide
| IUPAC_name = 4-(1,1-dioxothiazinan-2-yl)benzenesulfonamide
| image = Sultiame.svg
| image = Sultiame.png
 
<!--Clinical data-->
| tradename = 
| Drugs.com = {{drugs.com|international|sultiame}}
| pregnancy_AU = D
| pregnancy_US = D
| 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
| CAS_number = 61-56-3
| ATC_prefix = N03
| ATC_prefix = N03
| ATC_suffix = AX03
| ATC_suffix = AX03
| PubChem = 5356
| PubChem = 5356
| C = 10 | H = 14 | N = 2 | O = 4 | S = 2
| 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  
| molecular_weight = 290.0395 g/mol
| molecular_weight = 290.0395 g/mol
| bioavailability = 100% (oral)
| smiles = O=S2(=O)N(c1ccc(cc1)S(=O)(=O)N)CCCC2
| protein_bound = 29%
| InChI = 1/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)
| metabolism = [[Liver|Hepatic]] secretion
| InChIKey = HMHVCUVYZFYAJI-UHFFFAOYAA
| elimination_half-life = 24 hours
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| excretion = Fecal (10%) and [[Kidney|renal]] (90%)
| 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)
| routes_of_administration = Oral
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| legal_UK = POM
| StdInChIKey = HMHVCUVYZFYAJI-UHFFFAOYSA-N
| legal_US = Rx-only
| pregnancy_AU = D
| pregnancy_US = D
}}
}}
'''Sultiame''' ([[International Nonproprietary Name|rINN]], also known as '''sulthiame''') is a [[sulfonamide]] and [[inhibitor]] of the [[enzyme]] [[carbonic anhydrase inhibitor|carbonic anhydrase]]. It is used as an [[anticonvulsant]].
__NOTOC__
 
{{SI}}
 
{{CMG}}
 
==Overview==
'''Sultiame''' ([[International Nonproprietary Name|rINN]], also known as '''sulthiame''') is a [[sulfonamide (medicine)|sulfonamide]] and [[Enzyme inhibitor|inhibitor]] of the [[enzyme]] [[carbonic anhydrase inhibitor|carbonic anhydrase]]. It is used as an [[anticonvulsant]].


==History==
==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 [[USA]]. The brand was transferred to Desitin GmbH in 1993 and is sold in several European countries, in [[Israel]], [[Japan]], and [[Australia]].
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 [[USA]]. The brand was transferred to [[Desitin Arzneimittel GmbH|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>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=4386877&ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Hansen JM et al. ''Sulthiame (Ospolot) as inhibitor of diphenylhydantoin metabolism''. Epilepsia 1968;9:17-22.]</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>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=4386877&ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Green JR et al. ''Sulthiame: Evaluation as an anticonvulsant''. Epilepsia 1974;15:329-49.]</ref>, 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>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=2906619&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Doose H et al. ''Benign partial epilepsy - treatment with sulthiame''. Dev Med Child Neurol 1988;30:683-4.]</ref>. Today,  sulthiame is the drug of choice for benign focal epilepsies of childhood (e.g., Rolandic epilepsy) in the [[German language|German]]-speaking countries and Israel<ref>[http://www.epi.ch/isfiles/e1_2003.pdf Wohlrab G. ''Epilepsiebehandlung im Kindes- und Jugendalter: Kontinuität und Wandel''. Epileptologie 2003;20:25-30.]</ref>. There is renewed interest in sultiame's other potential uses, e.g., in [[West syndrome]]<ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=14738417&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Debus OM et al. ''Sulthiame in the primary therapy of West syndrome''. Epilepsia 2004;45:103-8.]</ref> and other [[refractory]] epilepsies<ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12200218&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Koepp MJ et al. ''Sulthiame in adults with refractory epilepsy and learning disability: an open trial''. Epilepsy Res 2002;50:277-82.]</ref>
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>Hansen JM, Kristensen M, Skovsted L. ''Sulthiame (Ospolot) as inhibitor of diphenylhydantoin metabolism''. Epilepsia 1968;9:17-22. PMID 4386877</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>Green JR et al. ''Sulthiame: Evaluation as an anticonvulsant''. Epilepsia 1974;15:329-49. PMID 4386877</ref> 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>Doose H et al. ''Benign partial epilepsy - treatment with sulthiame''. Dev Med Child Neurol 1988;30:683-4. PMID 2906619</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>Wohlrab G. [http://www.epi.ch/_files/Epileptologie_(PDF)/E1_2003.pdf ''Epilepsiebehandlung im Kindes- und Jugendalter: Kontinuität und Wandel''.] Epileptologie 2003;20:25-30.</ref> There is renewed interest in sultiame's other potential uses, e.g., in [[West syndrome]]<ref>Debus OM et al. ''Sulthiame in the primary therapy of West syndrome''. Epilepsia 2004;45:103-8. PMID 14738417</ref> and other [[refractory]] epilepsies<ref>Koepp MJ et al. ''Sulthiame in adults with refractory epilepsy and learning disability: an open trial''. Epilepsy Res 2002;50:277-82. PMID 12200218</ref>


==Indications==
==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.
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.


==Adverse effects==
==Adverse effects==


The more common adverse effects are [[ataxia]], [[paraesthesia]] of face and limbs, [[hyperpnoea]], [[dyspnoea]], and [[anorexia]]. Less common adverse effects include giddiness, rash, [[Stevens-Johnson syndrome]], [[nausea]], weight loss, [[leukopenia]], headache, psychic changes, depression, drooling, increased pain, frequency of fits, [[insomnia]], [[status epilepticus]]. Disturbances in [[calcium]] and [[vitamin D]] [[metabolism]] have been occasionally reported after long-term use.
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, psychic changes, depression, drooling, increased pain, frequency of fits, [[insomnia]], [[status epilepticus]]. Disturbances in [[calcium]] and [[vitamin D]] [[metabolism]] have been occasionally reported after long-term use.


==Interactions==
==Interactions==
Line 39: Line 76:
[[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 [[dialysis]] may help in case of 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 [[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).]]
p-Aminobenzenesulfonamide can be alkylated by ω-chlorobutylsulfonyl chloride in base via presumed intermediate, which spontaneously cyclizes to give sulthiame.
== References ==
== References ==
<references/>
{{reflist|2}}


{{Anticonvulsants}}


{{Anticonvulsants}}
[[Category:Anticonvulsants]]
[[Category:Anticonvulsants]]
[[Category:Sulfonamides]]
[[Category:Sulfonamides]]
[[Category:Carbonic anhydrase inhibitors]]
[[Category:Carbonic anhydrase inhibitors]]
 
[[Category:Thiazines]]
[[de:Sultiam]]
[[Category:Drug]]

Revision as of 15:03, 10 April 2015

Sultiame
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability100% (oral)
Protein binding29%
MetabolismHepatic secretion
Elimination half-life24 hours
ExcretionFecal (10%) and renal (90%)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC10H14N2O4S2
Molar mass290.0395 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Sultiame (rINN, also known as sulthiame) is a sulfonamide and inhibitor of the enzyme carbonic anhydrase. It is used as an anticonvulsant.

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 USA. 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 partial epilepsy in the 1960s and 1970s and was often used in combination with the established anticonvulsant phenytoin. 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,[1] 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,[2] resulted in a quick decline of sultiame's use. It was only in 1988, that the German child neurologist Hermann Doose discovered its specific effects in benign focal epilepsies of childhood.[3] Today, sulthiame is the drug of choice for benign focal epilepsies of childhood (such as benign rolandic epilepsy) in the German-speaking countries and Israel.[4] There is renewed interest in sultiame's other potential uses, e.g., in West syndrome[5] and other refractory epilepsies[6]

Indications

Historically, sultiame has been used to treat partial seizures. In Australia, it is currently registered for behavioural disorders associated with epilepsy; hyperkinetic behaviour; temporal lobe epilepsy; myoclonic seizures; grand mal attacks; and Jacksonian seizures.[7] In contrast to other sulfonamide drugs, sultiame is devoid of antibacterial activity.

Adverse effects

The more common adverse effects are ataxia, paraesthesia of face and limbs, hyperpnoea, dyspnoea, and anorexia. Less common adverse effects include giddiness, rash, Stevens–Johnson syndrome, nausea, weight loss, leukopenia, headache, psychic changes, depression, drooling, increased pain, frequency of fits, 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 must not be consumed during treatment.

Overdose

Vomiting, hypotension, headache, vertigo, ataxia, metabolic acidosis with hyperpnoea and catatonic state may occur. There is no specific antidote. It is not known whether dialysis may help in case of overdose.

Synthesis

Sultiame synthesis: B. Helferich and R. Behnisch, Template:US Patent (1959).

p-Aminobenzenesulfonamide can be alkylated by ω-chlorobutylsulfonyl chloride in base via presumed intermediate, which spontaneously cyclizes to give sulthiame.

References

  1. ↑ Hansen JM, Kristensen M, Skovsted L. Sulthiame (Ospolot) as inhibitor of diphenylhydantoin metabolism. Epilepsia 1968;9:17-22. PMID 4386877
  2. ↑ Green JR et al. Sulthiame: Evaluation as an anticonvulsant. Epilepsia 1974;15:329-49. PMID 4386877
  3. ↑ Doose H et al. Benign partial epilepsy - treatment with sulthiame. Dev Med Child Neurol 1988;30:683-4. PMID 2906619
  4. ↑ Wohlrab G. Epilepsiebehandlung im Kindes- und Jugendalter: Kontinuität und Wandel. Epileptologie 2003;20:25-30.
  5. ↑ Debus OM et al. Sulthiame in the primary therapy of West syndrome. Epilepsia 2004;45:103-8. PMID 14738417
  6. ↑ Koepp MJ et al. Sulthiame in adults with refractory epilepsy and learning disability: an open trial. Epilepsy Res 2002;50:277-82. PMID 12200218
  7. ↑ Pharmalab Pty Ltd. Product Information Ospolot (Sulthiame).

Template:Anticonvulsants

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