title: Central antitussive effect of codeine in the anesthetized rabbit.
abstract: BACKGROUND
  Codeine represents a commonly used drug to suppress cough. Central antitussive effect of codeine has been confirmed in a number of animal studies. However, available data related to antitussive activity of codeine in rabbits are very limited.
  
  
  OBJECTIVE
  We investigated the effects of codeine on cough, single expiratory responses (expiration-like reflex) induced by mechanical tracheo-bronchial stimulation, and on the sneeze reflex in the anesthetized rabbit.
  
  
  METHODS
  Twenty pentobarbitone anesthetized spontaneously breathing rabbits were used for the study. Increasing doses of codeine (codeinum dihydrogenphosphate, Interpharm) were injected intravenously (iv); 0, 0.15, 0.76, and 3.78 mg/kg of codeine dissolved in saline, 0.25 ml/kg) or intracerebroventricularly (icv); 0, 0.015, 0.076, and 0.378 mg/kg of codeine dissolved in artificial cerebrospinal fluid, 0.033 ml/kg.
  
  
  RESULTS
  Both iv and icv injections of codeine led to a dose-dependent reduction of coughing provoked by tracheo-bronchial stimulation; however, the doses differed substantially. The effective cumulative dose for a 50% reduction in the number of coughs was 3.9 and 0.11 mg/kg after iv and icv administration of codeine, respectively; representing about 35-fold higher efficacy of the icv route. The numbers of expiration-like responses and sneeze reflex responses remained unchanged.
  
  
  CONCLUSIONS
  The study confirmed the central antitussive effect of codeine, but showed a low sensitivity of sneeze and expiration reflex to codeine. We validated the experimental model of an anesthetized rabbit for studies on central antitussive action.
authors.affiliation: Institute of Medical Biophysics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. simera@jfmed.uniba.sk
authors.forename: Michal
authors.initials: M
authors.lastname: Simera
authors.forename: I
authors.initials: I
authors.lastname: Poliacek
authors.forename: J
authors.initials: J
authors.lastname: Jakus
mesh_terms: D000758:Anesthesia; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003061:Codeine / Q000494:pharmacology*; D004576:Electromyography; D005260:Female; D008297:Male; D011817:Rabbits
chemical_list: D000996:Antitussive Agents; D003061:Codeine