Effect of Some Barbiturates on Tissues In vitro.

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Abstract
Hanging drop tissue cultures of spinal cord from chicks incubated for 9 days were used to test the inhibitory action of various barbiturates on the outgrowth of nerve fibers. Using concentrations of 1:800, 1:1600, 1:3200, 1:6400, 1:8000 and 1:12,800, total inhibition was obtained at 1:6400 for Seconal Sodium, and at 1:3200 for both Pentobarbital Sodium and Sodium Amytal. The convulsive, lethal and anaesthetic dose of 14 other barbiturate compounds was generally well correlated with in vitro estimates of toxicity. However, some notable exceptions were found. For example, the lethal dose of 3,3-dimethyl allyl ethyl barbituric acid was 8.84 ± 0.32 mg/kg; and the second most damaging compound tested in vivo, but belonged to the least toxic group tested in vitro. In contrast, 3,3-dimethyl allyl allyl thiobarbituric acid which had a lethal dose of 94.08 ± 8.47, proved to be the most toxic member of the entire series in terms of outgrowth of living tissue. Corresponding cultures using fibroblast outgrowth from chick heart fragments generally proved somewhat more resistant to barbiturates than fiber outgrowths from cord explants. These results suggest that the survey of drug toxicity should include studies on particular tissues in addition to estimates of gross lethal effects.

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