Ampakines: Selective AMPA receptor modulators with potential benefits

Yıl 2012, Cilt: 2 Sayı: 4, 143 - 148, 30.01.2014

Salih Gümrü Feyza Arıcıoğlu

Öz

The study of the glutamatergic neurotransmitter system has received attention during the last decade in the pathophysiology and treatment of neuropsychiatric disorders. Glutamate is the major mediator of excitatory synaptic transmission in brain, and thereby contributes to important brain functions. Its ionotropic and metabotropic receptors function in a great variety of activities. The ionotropic glutamatergic receptors, ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) can trigger the activation of the whole system. Ampakines are a structurally diverse family of small molecules that selectively and positively modulate AMPA receptors, and causing fast, excitatory transmission in the brain. They enhance learning and memory processes by intervening communication between cortical regions. Besides, their function in regulating some growth factors, such as BDNF (brain-derived neurotrophic factor), explains their wide range of therapeutic potentials. Ampakines have given successful results in animal models of mood and neurodegenerative disorders, yet their clinical studies continue for a couple of molecules.

Key words: Glutamatergic system, AMPA receptors, ampakines, BDNF

Anahtar Kelimeler

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Ampakinler: Seçici AMPA reseptör modülatörlerinin olası faydaları

Öz

Glutamaterjik sistemin nöropsikiyatrik hastalıkların patofizyoloji ve tedavisindeki rolleri üzerine yapılan çalışmalara olan ilgi son yıllarda artmıştır. Eksitatör sinaptik iletimin ana mediyatörü olması sebebiyle, glutamatın beyin üzerindeki etkileri önemlidir. Glutamaterjik sistem, beyindeki iyonotropik ve metabotropik reseptörleri üzerinden gösterdiği geniş bir etki skalasına sahiptir. İyonotropik glutamat reseptörlerinden ?-amino-3-hidroksi-5-metil-4-izoksazolpropiyonik asit (AMPA) tipi reseptörler glutamaterjik sistemin oluşturduğu aktivasyonda rol oynar. Ampakinler, yapısal olarak farklı, AMPA reseptörlere selektif pozitif modülatör etkisi olan, küçük moleküllerden oluşan bir gruptur. Kortikal ağlar arasındaki iletişimi sağlayarak öğrenme ve bellek üzerinde pozitif etki sağladıkları halde, BDNF (beyin kaynaklı nörotrofik faktör) gibi nörotrofik faktörlerini regüle etmeleri terapötik potansiyelleri hakkında fikir vermektedir. Duygudurum bozuklukları ve nörodejeneratif hastalıkların hayvan modellerinde umutlandırıcı sonuçlar veren birçok ampakin molekülünün klinik çalışmaları sürmektedir.

Anahtar Kelimeler : Glutamaterjik sistem, AMPA reseptörleri, ampakinler, BDNF

Anahtar Kelimeler

Glutamaterjik sistem, AMPA reseptörleri, ampakinler, BDNF

Kaynakça

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