THE EFFECTS OF NUTRITIONAL DEFICIENCY ON RESPONSE TO THIOPENTAL

¹ Divisions of Pharmacology and Biological Chemistry, Hahnemann Medical College, Philadelphia, Pa.

The response of mice made deficient in protein and various B-complex vitamins to thiopental has been investigated by means of a new technique. This method measured the ability of the mouse to escape an unpleasant stimulus, a hot plate at 65°C., by climbing and holding onto a roughened, sharply inclined surface within certain time limits. With this technique, it was possible to measure intensity of response to thiopental, with actual responses in deficient animals including almost no effect, gross incoordination, loss of righting reflexes, profound anesthesia and death. When normal animals were tested, about 50 per cent successfully climbed the plane, while the remainder failed to climb although none were anesthetized. This end-point has been termed the Plane-Dose 50 (PD₅₀).

Mice made deficient in thiamine showed an essentially normal response. A moderately enhanced response was observed in animals made deficient in the B-complex vitamins, and was of about the same intensity as that seen in individual deficiencies of riboflavin, pyridoxine and pantothenic acid. Acute protein starvation also resulted in a moderately enhanced response to the standard test dose of thiopental. This was of the same magnitude as that seen in B-complex deficiency. The most enhanced response seen in these studies occurred with niacin deficiency, which was produced by use of a poor quality protein, low tryptophane diet with amino acid imbalance. Almost half of the niacin-deficient animals were anesthetized by the PD₅₀ dose of thiopental. The possible role of pyridine nucleotide-linked enzymes in the metabolic transformation of thiopental is discussed.

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