Sultiame (or sulthiame) is a sulfonamide and Enzyme inhibitor of the enzyme 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 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,
Indications
Historically, sultiame has been used to treat
Focal seizures seizures. In Australia, it is currently registered for behavioural disorders associated with
epilepsy; hyperkinetic behaviour; temporal lobe epilepsy;
Myoclonus ;
grand mal attacks; and Jacksonian seizures.
[ Pharmalab Pty Ltd. Product Information Ospolot (Sulthiame).] In contrast to other sulfonamide drugs, sultiame is devoid of
antibacterial activity.
Latest research is evaluating sultiamine for sleep apnea with early positive results.[ Medscape Oral Epilepsy Drug Eases Symptoms of OSA.]
Adverse effects
The more common adverse effects are
ataxia,
paraesthesia of face and limbs,
hyperpnoea,
dyspnoea, and
Anorexia nervosa. 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 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
Kidney dialysis may help in case of overdose.
Synthesis
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.
