Benzodiazepine receptors mediated anxiolytic-like effects of some 1,3,5-triaryl-4,5-dihydro-1h-pyrazole derivatives

Year 2016, Volume: 41 Issue: 2, 304 - 315, 30.06.2016

Özgür Can , Nazlı Turan Feyza Alyu

https://doi.org/10.17826/cutf.208627

Cited By: 3

Abstract

Purpose: Pyrazole is a heterocycle structure characterized by a five-membered ring of three carbon and two adjacent nitrogen atoms. Numerous compounds including pyrazole nucleus have been reported to possess wide diverse of pharmacological activities related to central nervous system. Based on this knowledge, in the present study, we planned to examine probable anxiolytic-like effects of eighteen 1,5-diaryl-3-[4-(methylsulfonyl)phenyl]-4,5-dihydro-1H-pyrazole derivative test compounds (2a-s) which previously synthesized by our research group.
Material and Methods: Anxiolytic activity potential of the test compounds (100 mg/kg, i.p) was evaluated in mice using hole-board and plus-maze tests. An antagonism study was conducted with flumazenil (3 mg / kg, ip), a GABA-benzodiazepine receptor blocker, in order to investigate mechanism of the anxiolytic-like activities.
Results: In the hole-board tests, compounds 2g, 2h, 2k and 2s significantly increased total number of the head-dipping behavior and number of the explored holes. In the plus-maze tests, the same compounds increased the time spent in the open arms and the number of entries into the open arms. These findings indicated that these four compounds have anxiolytic-like effects. Reference drug diazepam (1 mg/kg, i.p) also showed its anxiolytic activity in both of the tests, as expected. 
Conclusion: Benzodiazepine receptors mediated the anxiolytic-like effects of 2g, 2h, 2k and 2s coded 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivative compounds.

Keywords

Anxiolytic, 4, 5-dihydro-1H-pyrazole, flumazenil, hole-board test, elevated plus-maze tests

1,3,5-triaril-4,5-dihidro-1h-pirazol türevi bazı bileşiklerin benzodiazepin reseptörleri aracılıklı anksiyolitik-benzeri etkileri

Abstract

Amaç: Pirazol, üç karbon atomundan ve yan yana iki azot atomundan oluşan beş üyeli heterosiklik bir halka sistemidir. Literatürde pirazol çekirdeği taşıyan kimyasal bileşiklerin santral sinir sistemi üzerinde önemli bir etkinlik potansiyeli olduğuna ilişkin çok sayıda çalışmaya rastlamak mümkündür. Bu bilgiden hareketle, bu çalışmada, araştırma grubumuz tarafından sentezlenmiş olan onsekiz adet 1,5-diaril-3- [4- (metilsülfonil) fenil] -4,5-dihidro-1H-pirazol türevi bileşiğin (2a-s) olası ankiyolitik-benzeri aktiviteleri yönünden araştırılması planlanmıştır. 
Gereç ve Yöntem: Test bileşiklerinin (100 mg/kg, ip) anksiyolitik aktivite potansiyelleri, farelerde, delikli tahta ve yükseltilmiş artı-labirent testleri ile değerlendirilmiştir. Anksiyolitik-benzeri etkinliğe aracılık eden mekanizmaları araştırmak üzere GABA-A benzodiazepin reseptör blokörü flumazenil (3 mg/kg, i.p) ile antagonizma çalışması yapılmıştır.
Bulgular: Serideki 2g, 2h, 2k ve 2s kodlu bileşikler, farelerin delikli tahta testlerinde ölçülen toplam baş daldırma ve keşfedilen delik sayılarını anlamlı olarak artırmıştır. Aynı bileşikler, yükseltilmiş artı-labirent testi uygulanan farelerin hem açık kola giriş sayılarını hem de açık kolda kalma sürelerini anlamlı biçimde artırmıştır. Bu bulgular, söz konusu dört bileşiğin anksiyolitik-benzeri etkilere sahip olduğunu ortaya koymuştur. Diğer yandan, referans ilaç olarak kullanılan diazepam (1 mg / kg, ip) da hem delikli tahta hem de yükseltilmiş artı-labirent testlerinde beklenen anksiyolitik aktiviteyi göstermiştir. Sonuç: 2g, 2h, 2k ve 2s kodlu 1,3,5-triaril-4,5-dihidro-1H-pirazol türevlerinin anksiyolitik-benzeri etkilerine benzodiazepin reseptörleri aracılık etmektedir.

Keywords

anksiyolitik, 4, 5-dihidro-1H-pirazol, delikli tahta testi, flumazenil, yükseltilmiş artı labirent testi

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