OPIOIDERGIC SYSTEM-MEDIATED ANTINOCICEPTIVE ACTIVITY OF TOFISOPAM

Öz

Objective: In this study, it was aimed to investigate the antinociceptive activity potential of Tofisopam and to elucidate the possible involvement of opioid system in this effect.
Material and Method: The antinociceptive efficacy potential of Tofisopam (25 and 50 mg/kg) was evaluated by hot-plate and acetic acid-induced writhing tests; while possible effects of this drug on the motor coordination of mice were evaluated with the Rota-rod tests.
Result and Discussion: Tofisopam at a dose of 50 mg/kg significantly prolonged the reaction times of mice in hot-plate tests and reduced the number of writhing behaviors in writhing tests. These findings indicated that Tofisopam has antinociceptive activity mediated by central and peripheral mechanisms. Tofisopam did not change the motor activities of mice. Pre-administration of naloxone to investigate the possible involvement of opioid receptors in the antinociceptive effect abolished the antinociceptive activity of Tofisopam. To elucidate the opioid receptor subtypes mediating the effect, mechanistic studies were carried out with naloxonazine (μ-opioid receptor blocker), naltrindole (δ-opioid receptor blocker) and nor-binaltorphimine (ҡ-opioid receptor blocker). All agents antagonized the antinociceptive effect of Tofisopam. Obtained findings revealed that Tofisopam at a dose of 50 mg/kg have antinociceptive activity mediated by μ-, δ- and ҡ-oipiod receptors.

Anahtar Kelimeler

• Analgesia
• acetic acid-induced writhing test
• hot-plate test
• opioidergic receptor
• tofisopam

TOFİSOPAM’IN OPİOİDERJİK SİSTEM ARACILIKLI ANTİNOSİSEPTİF ETKİNLİĞİ

Öz

Amaç: Bu çalışmada Tofisopam’ın antinosiseptif etkinlik potansiyelinin araştırılması ve bu etkiye opioiderjik sistemin olası katılımının aydınlatılması amaçlanmıştır.
Gereç ve Yöntem: Tofisopam’ın (25 ve 50 mg/kg) antinosiseptif etkinlik potansiyeli sıcak plaka ve asetik asid ile indüklenen kıvranma testleri ile araştırılmış; farelerin motor koordinasyonu üzerindeki olası etkileri ise Rota-rod testi ile değerlendirilmiştir.
Sonuç ve Tartışma: Tofisopam 50 mg/kg dozda, farelerin sıcak plaka testlerindeki reaksiyon sürelerini anlamlı ölçüde uzatmış; kıvranma testlerinde ise kıvranma davranışlarının sayılarını azaltmıştır. Bu bulgular Tofisopam’ın santral ve periferik mekanizmalar aracılıklı antinosiseptif aktiviteye sahip olduğuna işaret etmiştir. Tofisopam farelerin motor aktivitelerinde anlamlı bir değişikliğe neden olmamıştır. Antinosiseptif etkiye opioid reseptörlerin olası katılımını araştırmak amacı ile yapılan nalokson ön-uygulamaları Tofisopam’ın antinosiseptif aktivitesini ortadan kaldırmıştır. Etkiye aracılık eden opioid reseptör alt-tiplerinin aydınlatılması amacıyla naloksonazin (μ-opioid reseptör blokörü), naltrindol (δ-opioid reseptör blokörü) ve nor-binaltorfimin (ҡ-opioid reseptör blokörü) ile mekanistik çalışmalar yapılmıştır. Her üç ajan da Tofisopam’ın antinosiseptif etkisini antagonize etmiştir. Elde edilen bu bulgular Tofisopam’ın 50 mg/kg dozdaki antinosiseptif etkinliğine μ-, δ- ve ҡ-oipiod reseptörlerin aracılık ettiğini ortaya koymuştur.

Anahtar Kelimeler

• Analjezi
• asetik asid ile indüklenen kıvranma testi
• opioiderjik reseptör
• sıcak plaka testi
• tofisopam

Kaynakça

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