| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T73676 | ||||
| Target Name | Synaptic vesicle glycoprotein 2A | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Brivaracetam | Drug Info | IC50 = 80 nM | [536934] | |
| Action against Disease Model | Brivaracetam | UCB-34714 binds the LBS with pIC50 = 7.1. UCB-34714 induces the most potent and complete seizure suppression in animal models at doses devoid of side effects. Further testing ofUCB-34714 in animal models mimicking several other CNS diseases, such as neuropathic pain and essential tremor, also confirmed promising pharmacological activities | [552405] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Synaptic vesicle protein 2A (SV2A) is involved in neurotransmitter release and has been identified as the binding site for levetiracetam (Keppra), a novel antiepileptic drug. Homozygous SV2A (-/-) mice are not viable beyond a few weeks. In contrast, heterozygous SV2A (+/-) mice have a normal lifespan. We performed a behavioural phenotyping on SV2A (+/-) mice in a battery of tests: gross behavioural observation, spontaneous locomotor activity, sensori-motor coordination, acute pain sensitivity, exploration in an elevated plus-maze and an assessment of learning abilities in an inhibitory avoidance procedure. SV2A (+/-) mice were compared to age-matched, 2-month-old wild type controls. Overall, gross behaviour, spontaneous locomotor activity, sensori-motor coordination and acute pain sensitivity were comparable between wild type and SV2A (+/-) mice. When tested in a plus-maze, SV2A (+/-) mice displayed significant increased avoidance of open elevated arms whereas locomotor activity was not altered. Finally, both SV2A (+/-) and wild type mice showed comparable memory performance at the end of a multi-trial passive avoidance procedure. Interestingly, SV2A (+/-) mice exhibited increased avoidance of the lit area during the first sessions without foot shock. These results suggest an anxiety-like phenotype for SV2A (+/-) mice indicated by increased open-arm avoidance in the elevated plus-maze test as well as a shorter latency to escape from a lit area in the inhibitory avoidance procedure | [536934] | |||
| References | |||||
| Ref 536934 | Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43. Epub 2008 Nov 12. | ||||
| Ref 552405 | Discovery of 4-substituted pyrrolidone butanamides as new agents with significant antiepileptic activity. J Med Chem. 2004 Jan 29;47(3):530-49. | ||||
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