AMİTRİPTİLİNİN FAREDEKİ ANTİDEPRESAN BENZERİ ETKİSİNİN ADENOZİN A2A RESEPTÖR ANTAGONİZMASI İLE ARTIŞI

Yıl 2018, Cilt: 27 Sayı: 3, 205 - 210, 25.12.2018

Gülay Sezer

Öz

Amaç: Antidepresan bir ilaç olan amitriptilinin
periferal etkilerinde adenozinerjik sistemin rolü olduğu
ağrı modellerinde ve amitriptilinin neden olduğu
kardiyovasküler sistem toksisitesinde gösterilmiştir.
Ancak amitripitilinin antidepresan aktivitesinde
adenozin ya da adenozin A2A reseptör antagonismasının
rolü olup olmadığına dair bilgi bulunmadığı için bu çalışmayı planladık.
Metod: Deneylerde antidepresan benzeri etkiyi tayin
için Balb-c fareler üzerinde zorunlu yüzme testi uygulanmıştır. Farelere serum fizyolojik (kontrol grubu),
amitriptilin, SCH 58261 (A2A reseptör antagonisti), SCH
58261+amitriptilin, adenozin, adenozin+amitriptilin
intraperitoneal yoldan uygulanmıştır.
Bulgular: Amitriptilin her iki dozunda da kontrol grubuna göre hareketsiz kalma zamanını azaltmıştır.
Amitriptilinin hareketsiz kalma süresini azaltıcı etkisi
SCH 58261 ile ön muamele edildiğinde daha da artmıştır. Adenozin ile amitriptilin birlikte uygulandığında ise
amitriptilinin hareketsiz kalma süresini azaltıcı etkisi
azalmakla birlikte bu etki istatistiksel olarak anlamlı
bulunmamıştır.
Tartışma: Amitriptilinin faredeki antidepresan benzeri
etkisinde adenozinerjik sistemin rolü olabileceği ve A2A
receptor antagonisti ile ön muamele edildiğinde bu
etkinin artabileceği gösterilmiştir. Bu bulgunun özellikle ilaca dirençli hastalarda önemli olabileceğini düşünmekteyiz.

Anahtar Kelimeler

Amitriptilin, adenozin, adenozin A2A reseptör, antidepresan etki, fare

ADENOSINE A2A RECEPTOR ANTAGONISM INCREASED THE ANTIDEPRESSANT-LIKE EFFECT OF AMITRIPTYLINE IN MICE

Öz

Objective: The role of the endogenous adenosinergic
system in the peripheral effect of an antidepressant
drug, amitriptyline, has been demonstrated in pain
models and also in cardiovascular toxicity induced by
amitriptyline. We performed this study as there is no
information on whether adenosine or adenosine A2A
receptor antagonists have any effect on the
antidepressant-like activity of amitriptyline in mice.
Methods: Balb-c mice were used in experiments and
forced swimming test was used to evaluate the
antidepressant-like activity. Mice were injected with
saline (control), amitriptyline, SCH 58261 (A2A receptor
antagonist), SCH 58261 + amitriptyline, adenosine,
adenosine + amitriptyline, intraperitoneally.
Results: Amitriptyline decreased immobility time
compared to control group at both doses. SCH 58261
did not produce antidepressant like effect in the applied
dose alone. Pretreatment of amitriptyline with SCH
58261 produced stronger inhibition of immobility time
than amitriptyline induced alone in the same dose. Coadministration of adenosine with amitriptyine,
however, it was not decreased the anti-immobility effect
of amitriptyline. However, it was not statistically
significant.
Conclusion: It has been demonstrated that
adenosinergic system may have a role in the
antidepressant-like activity of amitriptyline in mice, and
pretreatment with the A2A receptor antagonist may
induce a more pronounced antidepressant-like activity.
We are of the opinion that this finding may be of
particular importance in the case of drug resistant
patients. 

Anahtar Kelimeler

Amitriptyline, adenosine, adenosine A2A receptor, antidepressan activity, mouse

Kaynakça

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