Central antitussive effect of codeine in the anesthetized rabbit

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. MATERIALS AND 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.