ON THE PHARMACOLOGY OF HEXAETHYL TETRAPHOSPHATE

The pharmacologic actions and toxicity of HETP were studies in rabbits, mice and in intact and anesthetized dogs. HETP produces muscarinic and nicotinic effects of relatively brief duration. That the action is more lasting than these brief observable signs would suggest is shown by the cumulative effects of repeated injections. The lethal action of toxic doses of HETP in unprotected animals is exerted within 15-30 minutes by intravenous injection, and within 1-2 hours by the intramuscular route. Animals that survive these periods eventually recover. Death is due to respiratory failure from marked bronchoconstriction and increased bronchial secretion. After atropinization, the respiratory failure results probably from direct central depression or the curariform action of acetylcholine. Atropine is an effective antagonist of the muscarinic effects of HETP and offers protection against approximately three lethal doses of the drug. HETP has a potent anticholinesterase action which is responsible for most of the effects of the drug. In vitro , the inhibition of cholinesterase appears to be mainly irreversible, although the in vivo evidence indicates that there is a fairly significant labile component which allows the liberation of sufficient cholinesterase to enable the animal to recover within a short time. HETP, therefore, occupies a position midway between DFP and prostigmine. The differences between the actions of HETP and DFP were discussed.