EFFECTS OF TRIMETHADIONE ON SYNAPTIC TRANSMISSION IN THE SPINAL CORD; ANTAGONISM OF TRIMETHADIONE AND PENTYLENETETRAZOL

¹ Department of Pharmacology, University of Utah College of Medicine, Salt Lake City

Trimethadione (Tridione) has been studied in 18 spinal cord experiments in cats. The doses employed (100 to 400 mgm./kgm.) encompass the anticonvulsantnontoxic range for this species (200 to 300 mgm./kgm.). Tridione was observed not to affect the transmission of isolated impulses in the monosynaptic pathway but did exert a slight depressant effect upon polysynaptic activity. Post-tetanic potentiation is not affected by the drug.

The most pronounced effect of Tridione is to deepen depression following transmission of an impulse. This effect is due to the action of the drug at a presynaptic site. The increase in synaptic depression leads to a marked decrease in transmission during repetitive stimulation.

All the effects of Tridione on synaptic transmission are completely antagonized by appropriate doses of pentylenetetrazol (Metrazol). Conversely, excitant effects of Metrazol are completely antagonized by Tridione, and the two drugs may be titrated against one another over a wide range of doses.

Significant contrasts are revealed by a comparison of the effects of Tridione and diphenylhydantoin on synaptic transmission. From another viewpoint, marked differences in action between Tridione and a depressant drug such as pentobarbital are revealed. The significance of such comparisons with respect to the characteristic actions of these agents is discussed.