MUTUAL CROSS TOLERANCE AND TOLERANCE STUDIES WITH PENTOBARBITAL AND DELVINAL SODIUM IN RATS

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Abstract
Normal adult rats were injected intraperiton. with fresh aqueous solns. of each drug. Three stages of the hypnotic state were selected to determine the effect of each injn. The "onset of sleep" was the time from the injn. until the rat could not propel itself when stimulated. The "end of sleep" was the time from the injn. until the animal could be aroused to propel itself forward on stimulation. The "end of hypnosis" was the time from the injn. until the animal could walk a distance of about a meter without ataxia. 71 rats, made tolerant to delvinal-Na by a single injn. of 60 mg./kg. body wt. or 6 semi-weekly injns. of 60 mg./kg. were given 40 mg./kg. of pentobarbital-Na. The same amt. of pentobarbital-Na was given to a control group. The end of sleep came 3 min. earlier and the max. hypnotic time was 31 min. less in the animals that received a single 60 mg./kg. dose of delvinal-Na, than in the controls. In the 6 rats which had received the semi-weekly injns. of delvinal-Na, the sleeping time was 44 min. less, and the maximum hypnotic time was 95 min. less than that of the controls. The sleeping time was 21 min. less and the max. hypnotic time was 136 min. less in 3 rats after the intraperiton. admn. of 60 mg./kg. of delvinal-Na after 3 semi-weekly injns. of 40 mg./kg. pentobarbital-Na as compared to 20 controls. Similarly the sleeping time was 35 min. less and the max. hypnotic time was 56 min. less in 7 rats that received 6 semi- weekly injns. of 40 mg./kg. pentobarbital-Na. Both the sleeping time and the max. hypnotic time were reduced by 50% in the 10 rats that were first made tolerant to pentobarbital-Na by 3 and 6 semi-weekly injns., then were given a 60 mg./kg. dose of del-vinal-Na, and finally were given repeated doses of 40 mg./kg. of pentobarbital-Na. The authors thus proved a mutual cross tolerance between pentobarbital-Na and delvinal-Na in rats.