Effects of haloperidol on ventilation during isocapnic hypoxia in humans

Exposure to isocapnic hypoxia produces an abrupt increase in ventilation [acute hypoxic ventilatory response (AHVR)], which is followed by a subsequent decline [hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake, haloperidol has been reported to increase AHVR and almost entirely abolish HVD. To investigate whether this occurs in humans, the ventilatory responses of 15 healthy young volunteers to 20 min of isocapnic hypoxia (end-tidal PO2 = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) and after oral haloperidol (Seranace, 0.05 mg/kg) on different days. Three subjects were unable to complete the study because of akathisia. AHVR was significantly greater with haloperidol compared with control (P < 0.01, analysis of variance). However, no significant change in HVD was found [control HVD = 9.3 +/- 1.6 (SD) l/min, haloperidol HVD = 9.9 +/- 2.1 l/min; P = not significant, analysis of variance]. We conclude that combined central and peripheral dopamine-receptor antagonism in humans with haloperidol produces a similar pattern of change to that reported previously with the peripheral antagonist domperidone. We have been unable to show in humans a decrease in HVD by the centrally acting drug as observed in cats.