The irreversible narcotic antagonistic and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone

The fumaramate methyl ester derivatives of naltrexone (β-FNA) and oxymorphone (β-FOA) were both found to be reversible agonists on the guinea pig ileal longitudinal muscle preparation. In addition, β-FNA possessed an irreversible antagonistic effect against morphine whereas β-FOA had no such capacity. Analysis by pA₂ values revealed that β-FOa resembled pure agonists like morphine and enkephalin while β-FNA resembled the mixed agonist-antagonists like nalorphine and pentazocine. The antagonism by β-FNA was very selective in that it antagonized pure agonists but had little or no effect on the effects of either mixed agonists, ethylketocyclazocine or other non-opiate-type agonists like norepinephrine.