Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy

Autor: Evgenia Sitnikova, Elizaveta Rutskova, Kirill Smirnov
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 2, p 1477 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms24021477
Popis: Spike-wave discharges are the hallmark of idiopathic generalized epilepsy. They are caused by a disorder in the thalamocortical network. Commercially available anti-epileptic drugs have pronounced side effects (i.e., sedation and gastroenterological concerns), which might result from a low selectivity to molecular targets. We suggest a specific subtype of adrenergic receptors (ARs) as a promising anti-epileptic molecular target. In rats with a predisposition to absence epilepsy, alpha2 ARs agonists provoke sedation and enhance spike-wave activity during transitions from awake/sedation. A number of studies together with our own observations bring evidence that the sedative and proepileptic effects require different alpha2 ARs subtypes activation. Here we introduce a new concept on target pharmacotherapy of absence epilepsy via alpha2B ARs which are presented almost exclusively in the thalamus. We discuss HCN and calcium channels as the most relevant cellular targets of alpha2 ARs involved in spike-wave activity generation.
Databáze: Directory of Open Access Journals
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