Disposition and metabolism of [3H]pseudomorphine in the rat

Abstract

[3H]pseudomorphine (3H-PM) was prepared by the oxidation of [3H]morphine. A method for the estimation of 3H-PM in biological materials was developed with a minimal sensitivity of 2.5 ng/ml of biologic material. Following the subcutaneous injection of 3H-PM (10 mg/kg as free base) in rats, the levels of 3H-PM in brain and spinal cord over a 2-hr period ranged between 4.6 to 17.9 ng/g and 24 to 76.5 ng/g, respectively. No detectable levels of 3H-PM were present at 4 hr in the CNS. Peak plasma levels occurred at 30 min (501 ng/ml) and then fell rapidly with no detectable amounts present at 4 hr. About 78.2 per cent of the administered 3H-PM was accounted for in the urine and feces after 48 hr. Conjugated pseudomorphine was not detected in biological material, and direct chromatography of urine provided evidence for the presence of only free 3H-PM. The existence of a polar metabolite, however, cannot be precluded. Studies on rat brain extracts following the administration of [3H]morphine (10 mg/kg as free base) provided no evidence for the formation of pseudomorphine as an oxidative metabolite of morphine in vivo.