EFFECTS OF N-ALLYLNORMORPHINE UPON THE RESPIRATORY DEPRESSION DUE TO MORPHINE IN ANESTHETIZED MAN WITH STUDIES ON THE RESPIRATORY RESPONSE TO CARBON DIOXIDE

The antagonistic effect of N-allylnormorphine toward the respiratory depression produced by morphine in man was quantitatively recorded and studied.Even in the absence of hypoxia, concentrations of carbon dioxide in the blood during morphine depression were demonstrated which consistently were in excess of those demonstrated after the respiratory depression produced by morpbine had been antagonized by the administration of N-allylnormorphine.Correlations of respiratory activity with arterial carbon dioxide content indicated that, although the respiratory responses to carbon dioxide were similar both during morphine depression and after its antagonism by N-allylnormorphine, the arterial carbon dioxide content was consistently higher for corresponding degrees of respiratory activity before than after the administration of N-allylnormorphine.Evidence supporting the theory that N-allylnormorphine antagonizes morphine depression by the mechanism of drug competition and the displacement of morphine from certain receptors was discussed, and it was suggested that by such a mechanism N-allylnormorpnine restores the respiratory center to a more normal state of sensitivity to carbon dioxide and thus increases respiratory activity when given during morphine narcosis.Occasional indications of increased vasomotor activity and of analeptic effect following the administration of N-allynormorphine in the presence of morphine depression also were observed and considered compatible with the suggested mechanism of action of N-allylnormorphine.