ANALYSIS OF THE RELATIONSHIP BETWEEN DRUG-INDUCED CONVULSIONS AND MORTALITY IN RATS

¹ Department of Experimental Biology, The Weizmann Institute of Science, Rehovoth, and The Technion, Israel Institute of Technology, Haifa, Israel

The changes that occur in the correlation between drug-induced convulsions and mortality with dosage were studied in adult rats for several convulsant drugs.

Three types of positive correlations and also zero correlations were found. The correlation in the case of W-181 decreased monotonically and exponentially; with Thephorin it increased exponentially and monotonically, and similarly with high doses of Metrazol, whereas with lower doses of this drug, a zero correlation was fested. Strychnine gave a correlation which changed very little with dose, but a maximum correlation was given by a dose lying between the CD₅₀ and the LD₅₀, on both sides of which the correlation decreased monotonically, although very little. Nicotine gave a zero correlation for practically the entire "dosage range."

It was suggested that with drugs eliciting a positive correlation between convulsions and death, two types of action may be involved, one implicating more or less directly, and the other indirectly, vital systems. In one, mortality occurs as a result of the convulsions, and in the other, secondarily to them (W-181 and Thephorin, respectively). Although with most drugs this correlation changes with dosage, it is possible for it to stay relatively constant (as with strychnine).

With some drugs at least, at a certain wide dose range the correlation may be zero (nicotine, Metrazol), apparently because they can cause convulsions without implicating vital functions in a deleterious manner.