Abstract
The combined action of trimethadione and pentylenetetrazole was studied by determining, for six endpoints, the combined doses required for equieffectiveness; this was accomplished by experimentally establishing the course of the isobols of these endpoint effects.
The endpoints, determined in terms of median effective doses, were: threshold seizure, generalized clonic seizure, tonic extensor seizure, ejaculation, neurotoxicity, and death.
The field of combined doses studied extended up to 1.25 times the median neurotoxic dose of trimethadione and up to 1.75 times the LD50 of pentylenetetrazole.
Whereas the neurotoxicity of trimethadione was not significantly modified by pentylenetetrazole, the five other effects, despite their heterogeneity, were found to be all about equally antagonized by trimethadione.
The details of the interrelation between the combined actions, disclosed by this study, and the advantages of and requirements for the multiple isobolographic procedure employed are discussed.
Footnotes
- Received December 27, 1954.
- © 1955, by The Williams & Wilkins Company
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