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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, U.S. 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

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

UpToDate Contents

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1. 点頭てんかんのマネージメントおよび予後 management and prognosis of infantile spasms
2. 小児期の良性部分てんかん benign partial epilepsies of childhood

English Journal

Sulfonamide inhibition studies of the η-class carbonic anhydrase from the malaria pathogen Plasmodium falciparum.

Vullo D1, Del Prete S2, Fisher GM3, Andrews KT3, Poulsen SA3, Capasso C4, Supuran CT5.
Bioorganic & medicinal chemistry.Bioorg Med Chem.2015 Feb 1;23(3):526-31. doi: 10.1016/j.bmc.2014.12.009. Epub 2014 Dec 11.
The η-carbonic anhydrases (CAs, EC 4.2.1.1) were recently discovered as the sixth genetic class of this metalloenzyme superfamily, and are so far known only in protozoa, including various Plasmodium species, the causative agents of malaria. We report here an inhibition study of the η-CA from Plasm
PMID 25533402

Comparison of antiepileptic drugs, no treatment, or placebo for children with benign epilepsy with centro temporal spikes.

Tan HJ1, Singh J, Gupta R, de Goede C.
The Cochrane database of systematic reviews.Cochrane Database Syst Rev.2014 Sep 5;9:CD006779. doi: 10.1002/14651858.CD006779.pub2.
BACKGROUND: Benign Epilepsy with Centro Temporal Spikes (BECTS) is a common epilepsy syndrome with onset in childhood which almost always remits by adolescence. It is characterised by focal seizures associated with motor signs and somatosensory symptoms, at times progressing to become generalised. T
PMID 25190506

Individualized phenytoin therapy for pediatric Japanese epilepsy patients based on CYP2C9 and CYP2C19 genotypes.

Yamamoto Y1, Takahashi Y, Imai K, Miyakawa K, Ikeda H, Ueda Y, Yamaguchi T, Nasu H, Ohtani H, Shigematsu H, Kagawa Y, Inoue Y.
Therapeutic drug monitoring.Ther Drug Monit.2014 Aug 26. [Epub ahead of print]
BACKGROUND:: The aims of this study were to identify the target dose of phenytoin (PHT) and to compare the treatment continuation rate between patients receiving conventional therapy and patients receiving individualized therapy based on genotyping of the CYP2C9*3, CYP2C19*2, and CYP2C19*3 alleles.
PMID 25162219

Japanese Journal

難治性てんかんに対する sulthiame の効果

宮嶋智子,熊田知浩,木村暢佑,三國貴康,藤井達哉
脳と発達 41(1), 17-20, 2009-01-01
NAID 10023975586

P2-54 スルチアムが有効であったカルバマゼピン無効のローランドてんかんの2例(薬物治療4,一般演題(ポスター),てんかん制圧:新たなステージに向けて,第41回日本てんかん学会)

大府正治,児玉梨恵,井原由紀子,藤田貴子,中村紀子,友納優子,鶴澤礼実,井上貴仁,安元佐和,小川厚,友田靖子,廣瀬伸一,満留昭久
てんかん研究 25(3), 373, 2007-09-30
NAID 110006481268

Sulthiame in childhood epilepsy

BEN-ZEEV BRURIA,WATEMBERG NATHAN,LERMAN PINCHAS,BARASH ITSHAK,BRAND NATHAN,LERMAN-SAGIE TALLY
Pediatrics international : official journal of the Japan Pediatric Society 46(5), 521-524, 2004-10-01
NAID 10016543713

Related Pictures

epilepsy active ingredient sulthiame Systematic ( IUPAC ) name sulthiame 1 90 min lamotrigine 2 74 min is Acetazolamide, Sulthiame and Newer arghlblargh! 苏噻嗪片|Ospolot(Sulthiame Tablets Systemic inflammatory response syndrome Sultiame synthesis: B. Helferich and R

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リンク元

「スルチアム」

Sultiame
Systematic (IUPAC) name
	4-(1,1-dioxothiazinan-2-yl)benzenesulfonamide
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy; category	AU: D; US: D;
Legal status	UK: POM; US: ℞-only;
Routes	Oral
Pharmacokinetic data
Bioavailability	100% (oral)
Protein binding	29%
Metabolism	Hepatic secretion
Half-life	24 hours
Excretion	Fecal (10%) and renal (90%)
Identifiers
CAS number	61-56-3
ATC code	N03AX03
PubChem	CID 5356
DrugBank	DB08329
ChemSpider	5163
UNII	I00Q766CZ2
KEGG	D01787
ChEMBL	CHEMBL328560
Chemical data
Formula	C10H14N2O4S2
Molecular mass	290.0395 g/mol
	SMILES O=S2(=O)N(c1ccc(cc1)S(=O)(=O)N)CCCC2;
	InChI InChI=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) ; Key:HMHVCUVYZFYAJI-UHFFFAOYSA-N ;
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英: sultiame, sulthiame
商: オスポロット

[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).

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sulthiame