Influence of codeine on lobeline-induced respiratory reflexes and sensations and on ventilation with exercise in healthy subjects

In 15 healthy subjects, the effect of 60 mg oral codeine and placebo was examined on intravenously injected lobeline-elicited respiratory reflexes and sensations. Its influence was also studied on ventilation and appearance of distressful respiratory sensations with modest but incremental exercise. After placebo, tachypnoea and respiratory sensations were evoked with 12.1 ± 1.9 μg/kg of lobeline i.v. (mean threshold dose) and after codeine, by significantly higher doses i.e., 18.0 ± 3.1 μg/kg (P < 0.05). Additionally after codeine, in response to incremental doses of lobeline the respiratory reflex was notably attenuated and the magnitude of respiratory sensations, subdued. Dry cough seen in 66% of the subjects with suprathreshold doses of lobeline i.e., 22.0 ± 3.4 μg/kg (mean), appeared post codeine, with significantly higher doses i.e., 27.0 ± 3.9 μg/kg (mean) (P < 0.05) and in a fewer subjects (60%). Mean increase in minute ventilation at the end of 8 min of incremental treadmill walking after codeine was 21% less than after placebo (P < 0.05); 60% of the subjects continued to walk for an additional 4 min and the onset of respiratory discomfort was delayed by 1-5 min. This is the first report of an attenuation of lobeline-elicited respiratory reflexes and sensations that are attributable to J receptors (pulmonary C fibres) by a pharmacological entity. It also suggests that codeine decreased these receptors' known contribution to respiratory augmentation and motor inhibition during exercise, which was seen as a delay in the onset of, and a decrease in the magnitude of respiratory discomfort during treadmill walking and an increase in the duration walked by more than half the subjects.