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Interaction of oxotremorine with atropine, chlorpromazine, cyproheptadine, imipramine and phenoxybenzamine on the flexor reflex of the chronic spinal dog

Abstract

The central antimuscarinic actions of several drugs, atropine, phenoxybenzamine, cyproheptadine, imipramine and chlorpromazine, were determined by their ability to antagonize oxotremorine-induced facilitation of the electrically evoked flexor reflex and production of the steping reflex in the chronic spinal dog. The drug actions and interactions were determined by sequentially infusing the antagonist, methylatropine and oxotremorine and observing changes in flexor reflex amplitude. The facilitation of the flexor reflex and evocation of the steping reflex produced by oxotremorine in the methylatropine pretreated animal are thought to be due to a direct action on the spinal cord. Atropine, cyproheptadine, imipramine and chlorpromazine depressed the amplitude of the flexor reflex and phenoxybenzamine produced a slight enhancement. The interaction studies demonstrated that atropine almost completely prevented the spinal cord effects of oxotremorine while phenoxybenzamine showed no antagonism. Imipramine, chlorpromazine and cyproheptadine demonstrated the same relative degree of partial antagonism and antimuscarinic activity in the spinal cord. These findings suggest that facilitatory muscarinic cholinergic neurons may be present either as a parallel pathway in the segmental reflex or longitudinally oriented pathways in the spinal cord.

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Submitted in partial fulfillment of the requirements for the degree of Master of Science at the University of Kentucky.

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Vaupel, D.B., Martin, W.R. Interaction of oxotremorine with atropine, chlorpromazine, cyproheptadine, imipramine and phenoxybenzamine on the flexor reflex of the chronic spinal dog. Psychopharmacologia 30, 13–26 (1973). https://doi.org/10.1007/BF00422790

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Key Words

  • Oxotremorine
  • Atropine
  • Flexor Reflex
  • Chronic Spinal Dog
  • Cholinergic Mechanisms
  • Spinal Cord