title: The acute effects of mirtazapine on pain related behavior in healthy animals.
abstract: OBJECTIVE
  To investigate whether the tetracyclic antidepressant mirtazapine has a pain-suppressing effect in healthy animals.
  
  
  METHODS
  In the first step, Swiss albino female mice weighing 25-35 g were used. Eight groups each containing 8 mice were established as follows:- Control (saline), mirtazapine 5 mg/kg, 10 mg/kg, and 20 mg/kg, mirtazapine 10mg/kg and its combinations L-Nitro-L-Arginine Methyl Ester (L-NAME) 100 mg/kg, L-Arginine 100 mg/kg, naloxone 1 mg/kg, and cyproheptadine 50 ug/kg. This study was performed in the Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey during March, April, and May 2009. One hour after the drugs were given intraperitoneally, hot plate, tail clip, tail flick, and writhing tests were used for evaluating antinociceptive effects. In the second step, the brain hippocampus of Sprague Dawley type male rats weighing 250±20 g were isolated and 0.6 um hippocampus slices were obtained. In vitro groups were established as control, mirtazapine 3x10(-3)M, 4x10(-3)M, 5x10(-3)M, mirtazapine 4x10(-3)M and its combinations L-NAME, L-Arginine, naloxone, and cyproheptadine 4x10(-3)M.
  
  
  RESULTS
  Mirtazapine did not show central spinal analgesic activity, but had significant peripheral and biphasic central analgesic effects at the supraspinal level. In addition, there were no significant differences between the different groups in nitric oxide synthase levels on the brain slices.
  
  
  CONCLUSIONS
  The nitrergic pathway does not have an effect on the central antinociceptive activity of mirtazapine, while opiatergic and serotonergic pathways have a significant role.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey. fskilic@ogu.edu.tr
authors.forename: Fatma S
authors.initials: FS
authors.lastname: Kilic
authors.forename: Ali E
authors.initials: AE
authors.lastname: Dogan
authors.forename: Canan
authors.initials: C
authors.lastname: Baydemir
authors.forename: Kevser
authors.initials: K
authors.lastname: Erol
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001120:Arginine; D001522:Behavior, Animal / Q000187:drug effects; D003533:Cyproheptadine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D000078785:Mirtazapine; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000009:adverse effects; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D012702:Serotonin Antagonists; D008803:Mianserin; D003533:Cyproheptadine; D009270:Naloxone; D001120:Arginine; D000078785:Mirtazapine; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester