Pentilentetrazol ile Sıçanlarda Oluşturulan Deneysel Epilepsi Modelinde Oksolamin Sitratın antikonvulsan Etkisi

Yıl 2020, Cilt: 11 Sayı: 1, 92 - 99, 03.03.2020

Mümin Alper Erdoğan , Oytun Erbaş

Öz

Amaç: Dünya çapında milyonlarca kişi epilepsi hastası olarak sorun yaşamaktadır ve hastaların %25'inde şu anda mevcut bulunan antiepileptik ilaçlara karşı dirençli nöbetler gözlenmektedir. Bu nedenlerle, etkili ve henüz tolere edilebilen daha fazla sayıda antiepileptik ilaca ihtiyaç duyulmaya devam etmektedir. Oksolamin sitrat, pre-klinik verilere dayanarak antiepileptik aktiviteye sahip olabilen yaygın bir antitussif ilaçtır.

Materyal-Metot: Sıçanlar randomize bir şekilde intraperitoneal (i.p.) Oksolamin ile iki farklı dozda ve plasebo şeklinde tedavi edildi ve daha sonrasında güçlü bir nöbet indükleyici bileşik olan pentilentetrazole (PTZ) i.p. olarak maruz bırakıldı. Oksolaminin epilepsi için sıçan modelimizde antiepileptik özelliklere sahip olup olmadığını belirlemede sıçanların hemen sonrasındaki nöbet aktivitesi elektroensefalografi (EEG), Racine'nin konvülsiyon ölçeği (RCS) ve ilk miyoklonik jerk (TFMJ) zamanı ile değerlendirildi.

Bulgular: Plasebo ile karşılaştırıldığında, her iki dozda Oksolamin, nöbet aktivitesini önemli ölçüde inhibe etti. Ortalama EEG spike dalga yüzdesi % 75.3'ten (plasebo) % 35.8'e (düşük doz, p <0.01) ve %28.6'ya (yüksek doz, p <0.0001) azaldı. RCS, ortalama 5.7'den (plasebo) 4.7'ye (düşük doz, p <0.001) ve 3.3'e (yüksek doz, p <0.0001) düştü. TFMJ ortalama 62.5s'den (plasebo), 177.5s'ye (düşük doz, p <0.001) ve 223.3s'ye (yüksek doz, p <0.0001) yükseldi.

Sonuç: Yaygın bir antitussif ilaç olan Oksolamin sitrat, PTZ ile indüklenen status epileptikus sıçan modelinde nöbet aktivitesini baskılamaktadır. Refrakter epilepsi için devam eden etkili yeni tedaviler bulma gereksinimi göz önüne alındığında, oksolaminin antiepileptik olarak kullanılma olasılığı daha ileri düzeyde araştırılmalıdır.

Anahtar Kelimeler

Nöbet, Epilepsi, Oksolamin, Pentilentetrazol, Sıçan

Kaynakça

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