The effects of diisopropylfluorophosphonate in schizophrenia and manic depressive psychosis.

Diisopropylfluorophosphonate (DFP) is a drug which has been made available for physiological and pharmacological investigation as a result of researches carried out on the alkylfluorophosphonates by McCombie and Saunders (1946) for the Ministry of Supply. The anticholinesterase action of these compounds was recognized in 1941 by Adrian, Feldberg, and Kilby (1947). Later, Mackworth and Webb (1948) showed that DFP was the most active of such compounds, its anticholinesterase activity being 30 times that of eserine from which it also differs in inhibiting the enzyme irreversibly. DFP produces, in animals and man, effects similar to the muscarinic and nicotinic actions of acetylcholine. In addition Grob and others 1947(b)) have desdribed electroencephalographic (EEG) changes in man and also mental symptoms such as tremulousness, insomnia, and confusion. These have been attributed to an anticholinesterase action of the drug on the central nervous system. On this account, it was decided to study the effect of the drug in patients with characteristic functional psychoses, to determine its influence, if any, on the mental state of these cases, and to observe whether the physical and EEG changes produced differed from those previously reported in normal subjects. DFP dissolved in peanut oil was administered by intramuscular injection to 17 cases of schizophrenia and 9 cases of manic depressive psychosis. The schizophrenic group consisted of five paranoid, nine hebephrenic, one simple, and two catatonic patients. Of the manic depressives six were hypomanic, one was depressed, and two were in a state of remission. Data on age, weight, and duration of illness are presented in Table I. Thirteen schizophrenics and ninemanic depressives