title: Additive interaction of the cannabinoid receptor I agonist arachidonyl-2-chloroethylamide with etomidate in a sedation model in mice.
abstract: BACKGROUND
  Both propofol and volatile anesthetics have been reported to interact with the endocannabinoid system. The purpose of this study was to evaluate the effect of selective agonists for cannabinoid receptor types 1 and 2 on etomidate-induced sedation.
  
  
  METHODS
  A controlled, blinded, experimental study was performed in 20 mice that received intraperitoneal injections of etomidate, the cannabinoid1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the cannabinoid2 receptor agonist JWH 133 alone, and both ACEA and JWH 133 combined with etomidate. The cannabinoid1 receptor antagonist AM 251 and the cannabinoid2 receptor antagonist AM 630 were administered 10 min before the delivery of ACEA and JWH 133, respectively. Each drug combination was applied to 6-8 mice of these 20 study animals. Sedation was monitored by a Rota-Rod (Ugo Basile, Comerio, Italy). Isobolographic analysis was used for evaluation of pharmacologic interaction.
  
  
  RESULTS
  Single drug administration of etomidate and ACEA produced dose- and time-dependent decreased time on the Rota-Rod (P < 0.05). No sedative effect was seen after JWH 133. Etomidate-induced sedation was significantly increased and prolonged with ACEA (P < 0.05), but not with JWH 133. Isobolographic analysis revealed an additive interaction between ACEA and etomidate that was antagonized by the cannabinoid1 receptor antagonist AM 251. The cannabinoid1 receptor antagonist had no effect on etomidate alone.
  
  
  CONCLUSIONS
  Etomidate-induced sedation was increased and prolonged by activation of the cannabinoid1 receptor, but not of the cannabinoid2 receptor, in mice. However, this interaction was only additive.
authors: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany. meybohm@anaesthesie.unikiel.de
authors: Patrick
authors: P
authors: Meybohm
authors: Philipp-Alexander
authors: PA
authors: Brand
authors: Mike
authors: M
authors: Ufer
authors: Florian
authors: F
authors: Thiemann
authors: Markus
authors: M
authors: Steinfath
authors: Andrea
authors: A
authors: Paris
authors: Jens
authors: J
authors: Scholz
authors: Berthold
authors: B
authors: Bein
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D023421:Models, Animal; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000502:physiology; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D006993:Hypnotics and Sedatives; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; D005045:Etomidate