Some New Effects of Anticholinesterases in the Whole Animal, with Special Emphasis on the Hypothermia Inducing Action in the Rat

Abstract

At the turn of the century, the study of the effects of cholinesterase inhibitors began with the work of Pal and of Rothberger (see Werner & Kuperman, 1963) on physostigmine, and since then an immense amount of information has been brought together about the toxicological and pharmacological properties of these compounds. It is all the more surprising, therefore, that in the past 3 years several hitherto unknown effects of cholinesterase (ChE) inhibitors have been discovered in a much used laboratory animal like the rat. The three new phenomena which are the subject of this paper are: (i) heart failure in atropinized, anaesthetized, artificially ventilated rats injected with many times the LD₅₀ of organophosphorus ChE inhibitors such as DFP (di-isopropyl phosphorofluoridate) or sarin (isopropylmethylphosphorofluoridate); (ii) localized necrosis of striated muscle fibres at the end-plate region after injection of the rat with a just sublethal dose of an anti-ChE; and (iii) disturbance of the thermoregulation by just sublethal doses of ChE inhibitors which are able to pass the blood-brain barrier, leading to a marked hypothermia. Phenomena (i) and (ii) are mentioned only briefly because they have been amply described elsewhere and little further work has been done. Point (iii), however, has recently been actively studied and it is treated more extensively.