A mixed Nav blocker and KCa2 activator, as a potent novel anticonvulsant

Abstract

Current treatment options for epilepsy leave up to 30% of patients with recurring seizures and drug side effects, creating an urgent need for a strong anticonvulsant. Researchers at the University of California, Davis have identified a novel compound which shows potential as a treatment method for seizures as well as pain.

Full Description

Epilepsy is a complex neurological disorder, affecting well over 50 million people worldwide. Epilepsy is characterized by recurrent spontaneous seizures due to neuronal hyper-excitability and hyper-synchronous neuronal firing. Currently there are more than twenty antiepileptic drugs available on the market. Unfortunately, despite the broad variety of drugs available, about 30% of patients with epilepsy continue to experience seizures or suffer from unacceptable drug side effects such as drowsiness, behavioral changes, liver damage, and teratogenicity.

Researchers at the University of California, Davis have identified a novel potent and orally active anticonvulsant.  The compound demonstrates efficacy in seizure types that are difficult to treat. The novel feature of the invention is that the compound has dual mechanisms of action: sodium channel block and SK channel (KCa2 channel) activation. As a consequence of this, this compound has a broader effect than a typical sodium channel blocker. In addition to treating seizures, this novel compound has also been shown to reduce acute pain response in the formalin pain and the sciatic ligation models.

Applications

• Treatment for disorders characterized by neuronal hyperexcitability such as epilepsy and ataxia
• Treatment for acute and neuropathic pain

Patent Status

Features/Benefits

• Anticonvulsant with novel mechanism of action
• Potent and orally available (ED₅₀ in rodents 1-5 mg/kg)
• Broad spectrum antianticonvulsant to treat organophosphate induced seizures  
• Effective in pain models