title: In vivo and in vitro effects of neostigmine on gastrointestinal tract motility of horses.
abstract: OBJECTIVE
  To determine the response to neostigmine of the contractile activity of the jejunum and pelvic flexure and the effects of a continuous rate infusion (CRI) of neostigmine in horses.
  
  
  METHODS
  7 adult horses and tissue from 12 adult horses.
  
  
  METHODS
  A CRI of neostigmine (0.008 mg/kg/h) or placebo was administered to 6 horses in a crossover study design. Gastric emptying was evaluated by the acetaminophen test. The frequency of defecation and urination and the consistency and weight of feces were recorded throughout the experiment. The effect of neostigmine on smooth muscle contractile activity was evaluated in tissues from the jejunum and pelvic flexure. The effect of neostigmine and acetylcholine after incubation with muscarinic receptor antagonists (atropine and DAU 5884) and an acetylcholinesterase inhibitor (edrophonium) was also investigated in vitro.
  
  
  RESULTS
  No difference was observed between neostigmine and placebo for time to reach peak plasma acetaminophen concentration and absorption rate constant. A CRI of neostigmine increased fecal production and frequency of urination. Neostigmine induced a dose-dependent increase of contractile amplitude in jejunum and pelvic flexure muscle strips. Incubation of muscle strips with atropine and DAU 5884 inhibited the response to acetylcholine and neostigmine. Incubation of smooth muscle strips from the jejunum with edrophonium increased the response to acetylcholine and had no effect on the response to neostigmine in vitro.
  
  
  CONCLUSIONS
  A CRI of neostigmine increased fecal production and urination frequency in horses. A CRI of neostigmine did not decrease gastric emptying. Neostigmine stimulated contractile activity of jejunum and pelvic flexure smooth muscle strips in vitro.
authors.affiliation: Comparative Gastrointestinal Laboratory, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA. jenieto@ucdavis.edu
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Nieto
authors.forename: Betina
authors.initials: B
authors.lastname: Morales
authors.forename: Sawsan Z
authors.initials: SZ
authors.lastname: Yamout
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
authors.forename: Faye A
authors.initials: FA
authors.lastname: Harmon
authors.forename: Jack R
authors.initials: JR
authors.lastname: Snyder
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics; D000109:Acetylcholine / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006736:Horses; D008297:Male; D009388:Neostigmine / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D018712:Analgesics, Non-Narcotic; D018679:Cholinergic Agonists; D002800:Cholinesterase Inhibitors; D000082:Acetaminophen; D009388:Neostigmine; D000109:Acetylcholine