Characterization of the respiratory activity of (D-Ala2)methionine-enkephalinamide

The effects of central administration of (D-Ala2)methionine-enkephalinamide (EA) on respiration were studied in the unanesthetized rat. EA induced a dose-dependent depression of respiratory rate and tidal volume which was reversed by the subcutaneous administration of naloxone HCl (10 mg/kg). Increasing atmospheric CO2 concentration stimulated EA-induced respiratory depression and the peptide produced a parallel shift to the right of both the respiratory rate -- PaCO2 and tidal volume -- PaCO2 curves. Following chronic administration of EA tolerance to the respiratory depression was observed and chronic exposure to morphine produced partial tolerance to the respiratory depression induced by EA. It was concluded that EA desensitizes the central chemoreceptors to CO2 and the action of EA on respiration parallels that of morphine.