A PHARMACOLOGIC COMPARISON OF HEXAETHYL TETRAPHOSPHATE (HETP) AND TETRAETHYL PYROPHOSPHATE (TEPP) WITH PHYSOSTIGMINE, NEOSTIGMINE AND DFP

¹ Toxicity Laboratory and the Department of Pharmacology, The University of Chicago, Chicago, Illinois

1. The pharmacological effects of HETP and TEPP were compared with those of physostigmine, neostigmine and DFP on the blood pressure of anesthetized cats and dogs, on the electrocardiogram of anesthetized dogs, and on the isolated heart and intestine of the rabbit.

2. In these tests HETP and TEPP exhibited no qualitative differences in action from physostigmine and neostigmine.

3. With the exception of DFP, all of the drugs compared elicited qualitatively similar cardiovascular responses. DFP lacked a definite pressor effect and the onset of electrocardiogram changes was delayed.

4. Typical electrocardiographic changes following each drug were bradycardia, A-V block and dissociation, exaggeration and inversion of the T wave, and disappearance of the P wave.

5. The isolated rabbit heart was relatively insensitive to high perfusion concentrations or to single injections. Effective concentrations of each drug caused depression in amplitude without change in rate. The order of potency in this respect was DFP > HETP > TEPP > physostigmine.

6. The isolated rabbit intestine exhibited a high degree of sensitivity to all these agents. After a latent period the pendular movements were interrupted by a slow peristaltic type of activity. In their minimal effective concentrations these drugs bore the same relation to each other as in their reported anticholinesterase activities. Their effective concentrations were also of the same order as the 50 per cent cholinesterase inhibiting concentrations which have been reported.

7. These changes produced by HETP, TEPP, and DFP in the isolated intestine were not reversed by flushing the bath while the changes induced by physostigmine and neostigmine were reversed by flushing.

8. The tested pharmacologic actions of each of the five antiesterases were influenced in a similar way by other drugs, such as atropine, dibenamine, nicotine, procaine, and thiamine.

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