Sultiame

Sultiame

Sultiame
Systematic (IUPAC) name
4-(1,1-dioxothiazinan-2-yl)benzenesulfonamide
Clinical data
AHFS/Drugs.com
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Legal status
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability 100% (oral)
Protein binding 29%
Metabolism Hepatic secretion
Biological half-life 24 hours
Excretion Fecal (10%) and renal (90%)
Identifiers
CAS Registry Number  N
ATC code N03
PubChem CID:
DrugBank  YesY
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEMBL  YesY
Chemical data
Formula C10H14N2O4S2
Molecular mass 290.0395 g/mol
 N   

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

Contents

  • History 1
  • Indications 2
  • Adverse effects 3
  • Interactions 4
  • Overdose 5
  • Synthesis 6
  • References 7

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

  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. ^ .Product Information Ospolot (Sulthiame)Pharmalab Pty Ltd.