Farelerde pentilentetrazol ile oluşturulan epilepsiye endokannabinoidlerin etkisi

Yıl 2020, Cilt: 4 Sayı: 3, 209 - 215, 29.10.2020

Engin Yücel , Zühal Aktuna İsmail Semih Keskil

https://doi.org/10.30565/medalanya.690410

Öz

Amaç: Pentilentetrazol (PTZ) yaygın antikonvülzan olduğu varsayılan ilaçların değerlendirilmesi için kullanılan bir maddedir ve sinir liflerinin tekrarlayan şekilde uyarılmasını ve refrakter süresinin kısaltılmasını sağlar. Anandamid, nöronlarda sentezlenen ve depolarizasyon sırasında atılan bir endokannabinoiddir ve çok hızlı bir şekilde inaktive olur. Epilepsi gibi sinirsel bozukluklarda, yüksek anandamid düzeyleri gözlenmiştir. Etanol akut bir uygulama sonrası, antikonvülsif etkisi olan bir psikoaktif maddedir, ancak yüksek dozlarda tekrar tekrar verilmesi prokonvülsan etkiye yol açar. Bu çalışmada amacımız endokannabinoidlerin farelerde PTZ kaynaklı epileptik nöbetleri indükleyen anandamidin etkisini, kannabinoid reseptörlerinin tiplerini belirleyerek araştırmaktı.

Yöntemler: Küçük hayvan deney modelimizde, 25-35 gr ağırlığında otuz iki İsviçre albino erkek fare kullanıldı. Çalışma sırasında, deney hayvanları; kontrol, anandamid, anandamidin sentetik analoğu (WIN 55.212-2) ve etanol olarak rastgele dört gruba ayrıldı. Epileptik atakların sayısı, ilk epileptik atak süresi, epileptik atakların toplam süresi ve PTZ enjeksiyonundan sonraki ilk ataktaki bekleme, mortalite ve alevlenme gelişim süresi her grupla karşılaştırıldı.

Bulgular: WIN 55.212-2, anandamid ve etanol gruplarının tümünde mortalite oranı ve nöbet süresi anlamlı olarak daha düşüktü. PTZ enjeksiyonu öncesi etanol ve anandamid uygulandığında gecikme süreleri anlamlı olarak yüksek bulundu; ancak gruplar arasında bir fark yoktu. Bununla birlikte, benzer bir ilişki WIN 55.212-2 ve etanol arasında da mevcut değildi.

Sonuç: Endokannabinoid anandamid’in gözlenen antiepileptik etkisinin, çözücüsü olan etanol’ün etkisine bağlı olduğu söylenebilir; fakat bu etki de analoğu olan WIN 55.212-2 ile gözlenmemiştir. Her iki endokannabinoid de kannabinoid reseptörlerini etkilese de, bunların etkileri arasındaki söz konusu fark, onların farklı farmakokinetik, metabolizma ya da yıkım ürünlerine veya aktif metabolitlerine de bağlı olabilir.

Anahtar Kelimeler

Endokannabinoidler;, Pentilentetrazol;, Epilepsi;, Ethanol;, Anandamid;

Effects of endocannabinoids in pentylenetetrazole induced seizures in mice

Öz

Aim: Pentylenetetrazole (PTZ) is an agent widely used for the assessment of putative anticonvulsant drugs and is supposed to induce repetitive firing of nerve fibers as well as shorten the refractory period. Anandamide is an endocannabinoid synthesized in neurons, excreted by depolarization and inactivated very quickly. Ethanol is a psychoactive substance which has an anti convulsive effect after acute application, although repeated administrations of high doses lead to proconvulsant actions. In order to explore whether endocannabinoids are effective in the treatment of epilepsy or not, we aimed to study the effect of anandamide on PTZ induced epileptic seizures in mice by determining which types of cannabinoid receptors are.

Methods: In our small animal experimental model, thirty-two Swiss albino male mice weighing 25-35 g were used. During the study, the experimental animals were randomly divided into four groups as the control, anandamide, synthetic analogue of anandamide (WIN 55.212-2), and ethanol and the number of epileptic attacks, duration of the first epileptic attack, the total duration of the epileptic attacks and the latency time to the first attack after PTZ injection, mortality and the day of kindling development were compared in each group.

Results: The mortality rate and seizure duration were significantly lower in all of the anandamide, WIN 55.212-2 and ethanol groups. After pre-PTZ injection of ethanol and anandamide, latency periods were significantly higher, without any difference between the groups. However, a similar relationship was not present between WIN 55.212-2 and ethanol.

Conclusion: Our data showed that the antiepileptic effect of endocannabinoid anandamide observed was due to the its solvent, ethanol; however this effect was not found with its analogue WIN 55.212-2. Although both endocannabinoids resulted in interaction in the cannabinoid receptors, this difference may be the result of their different pharmacokinetics, metabolisms or degradation products and active metabolites.

Anahtar Kelimeler

Endocannabinoids;, Pentylenetetrazole;, Seizure;, Ethanol;, Anandamide;

Kaynakça

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