Carisbamate, a new carbamate for the treatment of epilepsy.
Carisbamate is a novel drug with neuromodulator activity that is currently under development for the treatment of epilepsy, diabetic neuropathy and neuralgia. The compound possessed a promising pharmacological profile in tests in vivo, and demonstrated broad anticonvulsant activity in preclinical studies, both elevating seizure threshold and preventing seizure spread. Carisbamate was also effective in protecting against spontaneous recurrent seizures in kainate-treated animals and in genetic models of epilepsy, and displayed antiepileptic and neuroprotective activity in the lithium-pilocarpine model of status epilepticus. In a phase I clinical trial, orally administered carisbamate demonstrated efficacy at high doses of 500 to 1000 mg. A phase II clinical trial confirmed that oral carisbamate was efficacious at a 300- to 1600-mg dose range. The preliminary evaluations of carisbamate in humans indicated complete absorption, extensive metabolism, and carbamate ester hydrolysis. The most frequently reported side effects associated with carisbamate are dizziness, headache, somnolence and nausea. In clinical trials, carisbamate did not display any significant interactions with commonly used antiepileptic drugs such as carbamazepine, valproate and lamotrigine. At the time of publication, a phase III clinical trial for carisbamate in the treatment of epilepsy was ongoing, as well as phase II trials in neuropathy and neuralgia. Data from preclinical brain injury studies with carisbamate and the analog RWJ-333369-A have also been reported. This drug profile will focus on the development of carisbamate in epilepsy.
Kulig
Katarzyna
K
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
Malawska
Barbara
B
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D018849:Controlled Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D010330:Patents as Topic
D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol