COMPARATIVE STUDY OF SEVERAL BARBITURATES WITH OBSERVATIONS ON IRREVERSIBLE NEUROLOGICAL DISTURBANCES

¹ Department of Pharmacology, Cornell University Medical College, New York, 21, New York

1. The approximate oral LD50 for several barbiturates in the cat were as follows: seconal, 50 mg. per Kg.; pentobarbital, 100; the barbiturate of sigmodal, 110; pernoston, 135; phenobarbital, 175. Attention is called to the extreme individual variation which limits the precision of the LD50 values.

2. The courses of action after oral administration of the approximate LD50 dose in the cat are substantially similar for seconal, pentobarbital, the barbiturate of sigmodal, and pernoston, namely, onset of ataxia in about 5 minutes, maximum narcosis in about 30 minutes, duration of the full effects for about 18 hours, and disappearance of ataxia in 2 to 3 days. The onset in the case of phenobarbital is somewhat slower, and the time for disappearance of ataxia is about 3 times as long.

3. The duration of action of the barbiturate of sigmodal in the dog is somewhat shorter than in the cat.

4. Large doses of secondary amyl-beta-bromallyl barbituric acid (barbiturate of sigmodal) produce an irreversible damage of the central nervous system resulting in motor, postural and reflex abnormalities in about 8 per cent of cats, but not in dogs.

5. Large doses of secondary butyl-beta-bromallyl barbituric acid (pernoston) also possess this action on the central nervous system to some degree in cats.

6. This action on the central nervous system of the cat was not observed with several other compounds free of the bromallyl group, namely, seconal, pentobarbital, and phenobarbital.

7. In view of the species differences, the large doses of the barbiturate which were used to produce these central nervous system effects, and the absence of reports of such effects from their therapeutic use, these observations in the cat may not be applicable to the use of these barbiturates in humans, at least in the range of hypnotic doses.