title: Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors.
abstract: OBJECTIVE
  To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock.
  
  
  METHODS
  Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 μg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1β were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in α7 nicotinic acetylcholine receptor (α7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock.
  
  
  RESULTS
  In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti-shock effect of combined anisodamine and neostigmine was abolished in α7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective α7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock.
  
  
  CONCLUSIONS
  The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of α7 nAChRs.
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Gu-fang
authors.initials: GF
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Jian-guo
authors.initials: JG
authors.lastname: Liu
authors.forename: Ding-feng
authors.initials: DF
authors.lastname: Su
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D004359:Drug Therapy, Combination; D055786:Gene Knockout Techniques; D006439:Hemodynamics / Q000187:drug effects; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009388:Neostigmine / Q000008:administration & dosage / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D012991:Solanaceous Alkaloids / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002800:Cholinesterase Inhibitors; C579166:Chrna7 protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011978:Receptors, Nicotinic; D012991:Solanaceous Alkaloids; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D064569:alpha7 Nicotinic Acetylcholine Receptor; C003922:anisodamine; D009388:Neostigmine