Abstract
Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol were synthesized and evaluated for analgesic activity. 1-Methyl-4-piperidinol 4-piperonylate (14) exhibited activity in the codeine range (mouse hot plate). In monkeys, 14 acted neither as a typical narcotic agonist nor as a typical antagonist and showed no physical dependence liability of the morphine type. The nonquaternary C-4 piperidinol esters exhibited marginal to virtually no binding to the opiate receptor in rat brain homogenates. The interaction of various functional groups of this series with potential binding sites of a nonopiate type receptor is discussed.

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