ucb L059, a novel anti-convulsant drug: pharmacological profile in animals

ONO‐2506 inhibits spike–wave discharges in a genetic animal model without affecting traditional convulsive tests via gliotransmission regulation

“…The majority of the established anticonvulsants were developed based on traditional convulsion screening tests, namely maximal electroshock seizure test (MES) (White et al, 2002) and pentylenetetrazol-induced seizure test (PTZ) (White et al, 2002), rather than on mechanism-directed drug design (Gower et al, 1992;Loscher and Honack, 1993;White et al, 2002). Levetiracetam, which has been shown to exhibit little anticonvulsant activity in MES and PTZ (Gower et al, 1992;Loscher and Honack, 1993), provides benefit in some individual patients with refractory epilepsy; however, drug refractoriness or intolerability is still a major problem in anticonvulsant medication (Otoul et al, 2005). Thus, neurocentric pharmacotherapy against epilepsy over several past decades did not provide a major breakthrough in overcoming refractoriness to antiepileptic drugs.…”

Molecular targets versus models for new antiepileptic drug discovery

“…Levetiracetam is not active in the traditional MES or s.c. MET AED screening models when conducted according to standard protocols (Klitgaard et al, 1998;Klitgaard, 2001). Nevertheless, the drug was discovered in another common screening model: audiogenic seizures in susceptible mice, and subsequently found to have activity in a range of chemoconvulsant models, including seizures induced by sub-maximal pentylenetetrazol doses (Gower et al, 1992), the 6-Hz model, and also various kindling models, including amygdala kindled rats, where it potently inhibits fully kindled seizures (Löscher and Hönack, 1993). Levetiracetam is active in a rat genetic model of absence epilepsy (Gower et al, 1995), which predicts its likely clinical activity in human absence epilepsy (Table 1).…”

“…Levetiracetam is active in a rat genetic model of absence epilepsy (Gower et al, 1995), which predicts its likely clinical activity in human absence epilepsy (Table 1). Levetiracetam also seems to have "antiepileptogenic" activity, in that it retards the development of pentylenetetrazol-kindled seizures (Gower et al, 1992) as well as conventional amygdalakindled seizures (Löscher et al, 1998). Gabapentin and levetiracetam are novel AEDs with distinct clinical profiles that were identified by presently available epilepsy screening models.…”

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam

“…However, in order to be effective in the treatment of myoclonic jerks a very high dose of piracetam (up to 16 g/day or more) is necessary. Levetiracetam proved to show a potent anticonvulsant effect on relatively low doses (5-30 mg/kg) in various models of generalized seizures in rats and mice [6]. It also proved to be effective in the pentylene tetrazol (PTZ) and bicuculline-induced seizures but ineffective in the standard version of the maximum electroshock and subcutaneous PTZ seizures tests [10].…”