首页 | 本学科首页   官方微博 | 高级检索  
     


Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model
Authors:Amir Mohammadzadeh,Pé  ter P. Lakatos,Mihá  ly Balogh,Ferenc Zá  dor,Dá  vid Á  rpá  d Kará  di,Zoltá  n S. Zá  dori,Korné  l Kirá  ly,Anna Rita Galambos,Szilvia Barsi,Pá  l Riba,Sá  ndor Benyhe,Lá  szló    les,Tamá  s Tá  bi,É  va Szö    ,Laszlo G. Harsing,Jr.,Mahmoud Al-Khrasani
Abstract:The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.
Keywords:neuropathic pain   NFPS   Org-25543   CSF glycine content   glycine transporter inhibitor combination
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号