Ventilatory effects of domperidone, a new dopamine antagonist, in anaesthetized rabbits

The ventilatory effects of domperidone (DP), a dopamine antagonist that does not cross the blood-brain barrier, were studied on rabbits anaesthetized with pentobarbitone. DP induced hyperventilation (+20%), which was not dose-dependent, without any marked change in arterial blood gases. This effect was abolished by previous transection of both carotid sinus nerves. On an average, steady state hypoxia (PaO2 approximately 45 mmHg for 5 min) doubled ventilation before, and increased itself threefold after DP (0.10 mg kg-1 i.v.). Prazosin (PZ, 0.1 mg kg-1 i.v.), an alpha 1-adrenoceptor antagonist, induced hyperventilation (+16%) but decreased systemic arterial blood pressure. PZ did not modify the ventilatory response to steady state hypoxia. In short, DP has a slight stimulating effect on resting ventilation and potentiates the ventilatory response to steady state hypoxia. This last effect would not depend on additional alpha 1-adrenoceptor antagonism of DP, as PZ does not change the ventilatory response to hypoxia.