New antiepileptic drug candidate

We offer a focused drug development project for a novel antiepileptic drug which targets a steady niche market. Our brand new approach promises the treatment not only for the traditional epileptic cases but also the ~30% of epilepsy cases which are irresponsive to current antiepileptic therapy. The size of current antiepileptic drugs was more than 11.5 billion US dollars in 2008 (collective product sales). Therefore, the potential market of our novel compounds is huge.

The target is the pharmacological manipulation of gap junction channels that participate in non-synaptic intercellular communication, which is a novel therapeutic approach and have been extensively studied by our collaborative partner.

Our pending patent application covers 105 new type antiepileptic compounds. The lead molecules were examined in vivo and showed excellent antiepileptic effects. In a 28-day toxicity study no toxicity was observed.

Effects of intravenous pretreatment of VID-45110 and of levetiracetam (LEV) on the latency of the first ictal period (A), on summated ictal activity (B) and on the average amplitude of seizure discharges (C) of cortical seizure activity induced by 4-AP (considered as control). Data are expressed as mean + SD. Stars indicate statistically significant changes. Significance criterion: p < 0.05.

Results

The Nested Chemical Library™ was used for preselecting potentially antiepileptic compounds.

We searched for molecules, which anticonvulsive effects were comparable and competitive to that of carbenoxolone. For this reason we carried out experiments in which the tested molecules were applied together with the GJ blocker, carbenoxolone. Our results showed that anticonvulsive effects of one of the tested molecule, the VID-45110 and of carbenoxolone to some extent overlapped with one another. The anticonvulsive effect of VID-45110 was a bit more intensive, but had considerably longer duration than that of carbenoxolone. This finding suggests that VID-45110 may exert its effects at least partially through the blocking of the GJ channels

We tested the effects of some VID-45110 analog compounds on the induction, maintenance and propagation of seizure discharges on the 4-aminopyridine (4-AP)-induced in vivo epilepsy model, which provided good opportunities to investigate the periods of both epileptogenesis and ictogenesis. In order to estimate the power of the possible antiepileptogenic and/or anticonvulsant efficacy of these compounds we compared their data to the well-known and wildly used AEDs (carbamazepin and levetiracetam) that were also tested on the 4-AP epilepsy model in identical circumstances. The results are shown in the following figures.