Umut Salgın GÖKŞEN, Nesrin Gökhan KELEKÇİ

6414

Antiinflamatuvar Tedavide Yeni Bir Yaklaşım: Siklooksijenaz ve 5-Lipooksijenazın Dual İnhibitörleri

Dual Siklooksijenaz-2/5-Lipooksijenaz COX-2/5-LOX inhibitörleri, araşidonik asitin iki major yolağı olan COX-2 ve 5-LOX yolaklarını inhibe eder. Bu iki yolağın blokajı ile inflamasyona neden olan prostanoit ve lökotrienlerin biyosentezi inhibe edilir. Klasik NSAİ ilaçların neden olduğu gastrointestinal Gİ sistemdeki yan etkiler bu bileşiklerde ya bulunmamakta ya da minimuma indirilmiştir. Yapılan çalışmalar sonucu COX ve 5-LOX enzimlerini aynı anda inhibe edebilecek çeşitli yapısal özelliklere sahip dual inhibitörler tasarlanmış ve bazıları preklinik klinik öncesi ya da klinik çalışmalara alınmıştır. Bunlar hem LT hem de prostanoitlerin biyosentezini inhibe ederek kuvvetli antiinflamatuvar etki göstermişlerdir. COX ve 5-LOX inhibitörlerinin kombinasyonu hem iki sınıf ilacın tek başına kullanılışlarından daha etkili olacak, aynı zamanda her iki enzimin tek bir ilaçla inhibisyonu ile güçlü dozlamadan ve ilaç etkileşimlerinden kaçınılmış olunacaktır. Bu nedenle dual COX-2/5-LOX inhibitörleri, inflamatuvar hastalıkların tedavisinde klasik NSAİ ilaçlara ve selektif COX-2 inhibitörlerine önemli bir alternatif sağlar.
Anahtar Kelimeler:

NSAİ, COX, 5-LOX, COX/5-LOX΄un dual inhibitörleri

A New Avenue in Anti-Inflammatory Therapy: Dual Inhibitors of Cyclooxygenase and 5-Lipoxygenase

Dual inhibitors are drugs able to block both the COX Cyclooxygenase and the 5-LOX 5-Lipoxygenase metabolic pathways. The biosynthesis of prostanoits and leukotriens giving rise to inflammation is inhibited by the blockage of the these two pathways. Dual inhibitors appear to be almost exempt from gastric toxicity, which is the most troublesome side effect of nonsteroidal antiinflammatory drugs NSAIDs . Various chemical families of dual COX/5-LOX inhibitors have been designed and some of them are currently undergoing preclinical or clinical development. The antiinflammatory effect of the combined COX/5-LOX inhibitors is higher than their individual antiinflammatory effects. Also it is forbeared from drug interactions and potent dosing by dual inhibition. Dual COX/5-LOX inhibitors constitute a valuable alternative to classical NSAIDs and selective COX-2 inhibitors for the treatment of inflammatory diseases.
Keywords:

NSAI, COX, 5-LOX, Dual inhibitors of COX/5-LOX,

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Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi-Cover
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1981
  • Yayıncı: Hacettepe Üniversitesi Eczacılık Fakültesi Dekanlığı
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