THE EFFECT OF DIFFERENT INTRAVENOUS INJECTION RATES UPON THE AD50, LD50 AND ANESTHETIC DURATION OF PENTOTHAL IN MICE, AND STRENGTH-DURATION CURVES OF DEPRESSION

¹ From the Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

1. The AD50 and LD50 of pentothal in mice were raised by decreasing the constant rate of intravenous injection.

2. The LD50/AD50 of pentothal varied from about 3 to 10, depending on the rates of injection used.

3. The [LD1/AD99–1]·100 (SSM of Foster) was found to decrease for the same drug (pentothal) with sufficiently decreased injection rate.

4. Evidence is presented that a given duration of anesthesia with pentothal tends to require a fixed fraction of the margin (difference) between the AD50 and LD50 determined with a common injection time, despite variations in this time which alter both the AD50 and LD50.

5. In the upper range of doses with pentothal, increased injection rate without increase in dose prolonged the anesthesia.

6. As compared to mice raised on a commercially compounded pellet diet, those raised on a diet of rolled oats, hay, and dog chow supplement were found to be progressively more resistant to pentothal (LD50 increased by as much as 50%) as the injection rate is decreased. One-half of this difference was obliterated by feeding the former mice oats and alfalfa for 6 days.

7. It is suggested that preliminary bioassays of intravenous anesthetics, and of hypnotics with immediate onset of action which are to be tested by the intravenous route, include the following factors: (1) LD50/AD50 over a range of specified rates of injection in order to detect possible maximum ratios; (2) the shape of the dosage-effect curves so that corresponding LD1/AD99 may be calculated; (3) the duration of anesthesia for a given fraction of the range between AD50 and LD50, and between AD99 and LD1; (4) the quality of the anesthesia.

8. The factors of injection rate and injection duration were found to be related in a fairly regular manner for threshold anesthesia and death, approximately according to the expression, y = Kx^–, in which varied from about 0.7 to 0.8.

9. The strength-duration curves of pentothal and amytal depression of the animal unit are similar to the strength-duration curves of excitation for the cellular unit.

10. It is suggested that the deviation in the shape of the depression strength-duration curves from the equilateral hyperbolic form may be accounted for by the more active participation in the response at slower injection rates of more remote body mechanisms which possess faster rates of detoxification.