BARBITURATE ANTAGONISM OF ISONIPECAINE CONVULSIONS AND ISONIPECAINE POTENTIATION OF BARBITURATE DEPRESSION

¹ Department of Pharmacology, The George Washington University School of Medicine, Washington, D. C.

1. It was found that barbital, phenobarhital, amytal, pentobarbital, and evipal (1/8; to 1/4; LD50 of the sodium salts) aborted convulsions and usually prevented death in mice and rabbits given an ordinarily lethal dose of isonipecaine.

2. When the dose of each barbiturate was increased to about 1/2; or 3/4; of its respective LD50 for antagonizing isonipecaine overdosage, it was found that the animals died of respiratory depression; convulsions did not precede death. Subsequently it was found that even when the amount of isonipecaine was reduced to about 1/8; its LD50, respiratory failure resulted in animals which had previously received an ordinarily tolerated barbiturate dosage (3/4;LD50).

3. Diphenylhydantoin (sodium salt) did not act like the barbiturates in the above respects.

4. It is concluded that isonipecaine barbiturate antagonism acts only in one direction. The barbiturates antagonize the lethal convulsive effects of isonipecaine, but isonipecaine potentiates the depressive properties of the barbiturates on respiration.