Evaluation of the Effects of Novel Nafimidone Derivatives on Thermal Hypoalgesia in Mice with Diabetic Neuropathy

Abstract

Objective: Diabetic neuropathy (DN) is a common complication in Diabetes Mellitus. The streptozotocin-induced diabetic rodent is the most commonly used animal model of diabetes and increased sodium channel expression and activity were revealed in this model. At this study, we evaluated the effect of three different nafimidone derivatives which have possible anticonvulsant activity on disorders of thermal pain sensation in diabetic mice. Study Design: Randomized animal experiment. Material and Methods: Mice were divided randomly into five groups (5 mice per group): Control, Diabetes, Dibetes+C1, Diabetes+C2, Diabetes+C3. We used hot and cold plate, and tail-immersion tests for assessment of thermal nociceptive responses. Results: Compared with the control group, the hot-plate response time and the number of paw liftings on cold plate as important indicators of loss of sensation increased, but no significant difference (p>0.05) was found in tail-immersion response time test in diabetes group. C3 compound moved it back to control group levels in the all of three tests. C1 and C2 compounds were effective only in cold-plate test. Conclusion: Nafimidone derivatives may be effective in the cases where epilepsy and diabetes occur together since it has shown efficacy against “loss of sensation” which evolves in diabetic neuropathy over time as well as its antiepileptic effect. Turkish Başlık: Diabetik Nöropati Oluşturulmuş Farelerde Yeni Geliştirilmiş Nafimidone Türevlerinin Termal Hipoaljezi Üzerine Etkileri Anahtar Kelimeler: Diabet, Diabetik nöropati, Duyu kaybı, Antikonvülzanlar, Na kanal blokerleri, Nafimidon türevleri Amaç: Nöropati, diabetes mellitusun sık karşılaşılan komplikasyonudur ve periferik duyusal polinöropatinin ensık nedenidir. İlelemiş periferik polinöropati ise azalmış ısı duyarlılığı ile ilişkilidir. Bazı antikonvülzanların, diabetin neden olduğu nöropatinin tedavisindeki etkinliği deneysel ve klinik çalışmalarla gösterilmiştir. Bu çalışmada antikonvülzan etkinliği bilinen nafimidon'un üç farklı türevinin diabet oluşturulmuş farelerdeki termal hipoaljezi üzerine olan etkilerini araştırdık. Gereç ve Yöntemler: Fareler kontrol, diabetik, diabetik+C1, diabetik+C2, diabetik+C3 olmak üzere beşerli beş grub'a ayrıldı. Bütün gruplara, termal hipoaljeziyi değerlendirmek için hot-plate, cold-plate ve tail-immersion testleri uygulandı. Bulgular: Diabet ve kontrol grupları karşılaştırıldığında, termal hipoaljezinin önemli bir göstergesi olarak hot-plate ve cold-plate testindeki pençe çekme süresi ve sayısı diabet grubunda anlamlı ölçüde artış saptandı (p<0.005), tail-immersion süresinde anlamlı bir değişiklik saptanmadı (p˃0.05). C3 türevi, üç test sonucununda kontrol grubu değerlerine gelmesini sağladı, C1 ve C2 türevleri ise sadece cold-plate testinde etkili oldular. Sonuç: Bu çalışmadaki test sonuçları, nafimidon türevi antikonvülzanların diabetin neden olduğu termal hipoaljezinin önlenmesinde etkili oldukları ve bu bileşiklerin gelecekte potansiyel tedavi ajanları olarak kullanılabilecekleri yönünde destekleyici bulgular olarak yorumlandı.

Keywords

• Diabet, diabetic neuropathy, loss of sensation, antiepileptic, Na channel blocker, nafimidone derivatives

Evaluation of the Effects of Novel Nafimidone Derivatives on Thermal Hypoalgesia in Mice with Diabetic Neuropathy

Öz

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