SULTHIAME

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H14N2O4S2
Molecular Weight	290.359
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)C1=CC=C(C=C1)N2CCCCS2(=O)=O

InChI

InChIKey=HMHVCUVYZFYAJI-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17588751
Curator's Comment: Description was created based on several sources, including http://www.cochrane.org/CD009472/EPILEPSY_sulthiame-add-therapy-epilepsy

Sulthiame is a potent inhibitor of carbonic anhydrase II, VII, IX, and XII. Sulthiame is an antiepileptic drug that is used widely in some European countries and in Israel. Sometimes it is used as an additional (add-on) antiepileptic medicine in non responders, alongside an existing antiepileptic medicine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Carbonic anhydrase II 88 Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17588751	Inhibitor 8297	7.0 nM [Ki]
Carbonic anhydrase VI 16 Target ID: CHEMBL3025 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17588751	Inhibitor 8297	6.0 nM [Ki]
Carbonic anhydrase IX 35 Target ID: CHEMBL3594 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17588751	Inhibitor 8297	43.0 nM [Ki]
Carbonic anhydrase XII 30 Target ID: CHEMBL3242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17588751	Inhibitor 8297	56.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: https://www.old.health.gov.il/units/pharmacy/trufot/alonim/Rishum_1_250060716.pdf	Primary		Approved 8429	OSPOLOT Approved Use Epileptic seizures of focal origin with or without secondary generalisation, especially benign partial epilepsies in childhood, such as rolandic epilepsy, pseudo-Lennox syndrome, bioelectric status epilepticus in non-REM sleep (ESES), Landau-Kleffner syndrome. Launch Date 1969

PubMed

Title	Date	PubMed
Phenytoin (Dilantin) intoxication.	1967	6081207
[Permanent cerebellar damage through temporary overdase of hydantoin].	1969 Jun 20	5785298
Delayed phenytoin idiosyncrasy.	1969 Nov 22	5354845
Carbamazepine-induced choreoathetoid dyskinesias.	1982 Jun	6811702
Progressive elevation of liver enzymes in a child treated with sulthiame.	2001 Jun	11521216
Reduction of voltage-operated sodium currents by the anticonvulsant drug sulthiame.	2001 May 4	11325350
Sulthiame in adults with refractory epilepsy and learning disability: an open trial.	2002 Aug	12200218
Carbamazepine versus sulthiame in treating benign childhood epilepsy with centrotemporal spikes.	2002 Dec	12593467
Serum concentrations of topiramate in patients with epilepsy: influence of dose, age, and comedication.	2002 Jun	12021627
Carbonic anhydrase inhibitor sulthiame reduces intracellular pH and epileptiform activity of hippocampal CA3 neurons.	2002 May	12027906
New antiepileptic drug therapies.	2002 Nov	12616686
Add-on treatment with pyridoxine and sulthiame in 12 infants with West syndrome: an open clinical study.	2002 Sep	12160666
[Electroclinical characteristics of Landau-Kleffner syndrome].	2003	14571670
Treatment with Sulthiame (Ospolot) in benign partial epilepsy of childhood and related syndromes: an open clinical and EEG study.	2003 Apr	12776234
The influence of sulthiame on EEG in children with benign childhood epilepsy with centrotemporal spikes (BECTS).	2003 Feb	12558577
Effect of antiepileptic drug monotherapy on crystalluria in children and young adults.	2003 Oct	14586614
Sulthiame in the primary therapy of West syndrome: a randomized double-blind placebo-controlled add-on trial on baseline pyridoxine medication.	2004 Feb	14738417
Sulthiame in childhood epilepsy.	2004 Oct	15491376
Management of Landau-Kleffner syndrome.	2005	16356025
[The risk of second seizure in children with benign childhood epilepsy with centrotemporal spikes without treatment--a prospective study].	2005	15813357
Effect of antiepileptic drug polytherapy on crystalluria.	2005 Feb	15664771
[Antiepileptic drugs in the treatment of autistic regression syndromes].	2005 Jan 15	15736083
Visually self-induced seizures sensitive to round objects.	2005 May	15857450
Perisylvian polymicrogyria in Landau-Kleffner syndrome.	2005 May 10	15883344
Children with rolandic epilepsy have abnormalities of oromotor and dichotic listening performance.	2005 Sep	16138667
Effect of antiepileptic drug monotherapy on urinary pH in children and young adults.	2006 Jan	15909204
P50 sensory gating deficit in children with centrotemporal spikes and sharp waves in the EEG.	2006 Jan 30	16246492
A single dose of sulthiame induces a selective increase in resting motor threshold in human motor cortex: A transcranial magnetic stimulation study.	2006 Nov	16930943
Recurrent absence status epilepticus (spike-and-wave stupor) associated with lamotrigine therapy.	2006 Sep	16970892
Sulthiame therapy for continuous spike and wave in slow-wave sleep.	2006 Sep	16939861
Treatment of epilepsy in Rett syndrome.	2007 Jan	17178248
Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: kinetic and X-ray crystallographic studies.	2007 Sep 1	17588751
Deterioration in cognitive function in children with benign epilepsy of childhood with central temporal spikes treated with sulthiame.	2008 Jan	18184938
Current trends in the treatment of infantile spasms.	2009	19557123
Rational treatment options with AEDs and ketogenic diet in Landau-Kleffner syndrome: still waiting after all these years.	2009 Aug	19682054
[Sulthiame treatment for patients with intractable epilepsy].	2009 Jan	19172811
Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES).	2009 Jun	19054417
Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates?	2009 Sep	19703035
2-Chloro-N-(4-sulfamoylphen-yl)acetamide.	2010 Jun 5	21587833
Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children.	2010 Mar	19709134
Respiratory alkalosis and metabolic acidosis in a child treated with sulthiame.	2010 Oct	20930598

Patents

Sample Use Guides

In Vivo Use Guide

The dosage must be established and monitored by the doctor on an individual basis. The maintenance dose is about 5 to 10 mg/kg body weight per day. It should be build up step-wise (tapered in) over a one-week period. Ospolot film-coated tablets have a dose notch. Due to the short half-life of sulthiame, the daily dose should as far as possible be spread over three single doses. If the daily dose is spread over the day in this way, constant plasma levels are to be expected after five to six days. Therapeutic plasma concentrations of sulthiame have not yet been determined.

Route of Administration: Oral

In Vitro Use Guide

In the majority of hippocampal CA3 neurons sulthiame (1.0-1.5 mM) reversibly decreased pHi. Sulthiame (1.0-2.5 mM) reversibly reduced the frequency of action potentials and epileptiform bursts.

Name

Type

Language

SULTHIAME

Official Name

English

SULTIAME [JAN]

Common Name

English

SULTIAME

Official Name

English

sultiame [INN]

Common Name

English

SULTIAME [MART.]

Common Name

English

SULTHIAME [MI]

Common Name

English

Sultiame [WHO-DD]

Common Name

English

TROLONE

Brand Name

English

OSPOLOT

Brand Name

English

P-(TETRAHYDRO-2H-1,2-THIAZIN-2-YL)BENZENESULFONAMIDE, S,S-DIOXIDE

Common Name

English

SULTHIAME [USAN]

Common Name

English

4-(Tetrahydro-2H-1,2-thiazin-2-yl)benzenesulfonamide, S,S-dioxide

Common Name

English

RIKER-594

Code

English

RIKER 594

Code

English

BENZENESULFONAMIDE, 4-(TETRAHYDRO-2H-1,2-THIAZIN-2-YL)-, S,S-DIOXIDE

Common Name

English

CONADIL

Brand Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

401213