title: Effects of the dopamine antagonists haloperidol and domperidone on the normoxic ventilatory response to CO2 in cats.
abstract: We investigated the effects of the dopamine antagonists haloperidol and domperidone on the ventilatory response following square-wave changes in end-tidal CO2 during normoxia in chloralose-urethane anaesthetized cats. In 7 cats these responses were measured before (control, 28 runs) and after the administration of 1 mg/kg haloperidol i.v. (26 runs) and in 8 other cats before (39 runs) and after 0.5 mg/kg domperidone i.v. (34 runs). Each response was separated into a slow central and a fast peripheral part by fitting two exponential functions to the measured ventilation. These functions have as parameters a CO2 sensitivity, a time constant, a time delay and an apnoeic threshold B (extrapolated PETCO2 of the steady-state response curve at zero ventilation). Haloperidol significantly diminished the peripheral (Sp) and the central (Sc) ventilatory sensitivity to CO2 and the B-value (P less than 0.001). The ratio Sp/Sc, the time constants and the time delays were not significantly changed. Domperidone only diminished the B-value significantly (P less than 0.001). Since domperidone does not readily cross the blood-brain barrier, its effect was a CO2 independent increase of the ventilation mediated by the peripheral chemoreceptors. Haloperidol exhibited, besides the peripheral stimulatory effect a depressant central effect due to an action on the central integrative structures, resulting in a proportional decrease of Sp and Sc.
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002415:Cats; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
chemical_list: D018492:Dopamine Antagonists; D002245:Carbon Dioxide; D004294:Domperidone; D006220:Haloperidol