Differential distribution of pentazocine- 3H and cis-3-chloroallylnorpentazocine- 3H in the cat

Abstract

The distribution of pentazocine, 2′-hydroxy-5,9-dimethyl-2-(3,3-dimethylallyl)-6,7-benzomorphan, a nonaddicting analgesic in man was compared in the cat with that of its chloroallyl isolog, cis-2-(3-chloroallyl)-2′-hydroxy- cis-5,9-dimethyl-6,7-benzomorphan (CHDB), also a strong analgesic but clinically unsuitable because of its dysphoric effects. Representative tissue samples were analyzed for tritium content by the oxygen flask combustion technique followed by liquid scintillation counting. Peak levels of either benzomorphan and metabolites occurred in blood and in brain tissue within 40 minutes of intramuscular injection of the tritiated drug. The molecular species representing nearly all the radioactivity in brain was the parent drug rather than a tritiated metabolite. There did not seem to be a blood to brain penetration barrier for either benzomorphan like that reported to exist for morphine. Preferential lipid solubility of the chloroallyl isolog, revealed by its partition coefficient, provided an explanation for its greater concentration in white matter rather than gray matter in contrast to the behavior of pentazocine in this respect. Differences in distribution were also noted in peripheral tissues of the cat. After 8 hours, over 50% of the absorbed chloroallyl isolog and its metabolites was sequestered in the bile. Pentazocine or its metabolites were especially concentrated in the liver and gastrointestinal tract. Furthermore, the distribution of these benzomorphans considered together was quite unlike that reported for morphine in the cat.