PHARMACOLOGICAL ACTION 



as to liberation of acetyl choline.^* The substance exhibited a different 

 polarographic behaviour from aneurine and is believed to be a reserve 

 substance connected with the disappearance of acetyl choline. 



Aneurine, in a dilution of i in 10,000, inhibited the vasoconstrictor 

 action of nicotine in frog vessels.^^ The action was due to the thiazole 

 moiety, and the site of the action was the myoneural junction in 

 striated muscles and the postganglionic nerve endings or muscle 

 elements of the vessel walls in smooth muscles. 



Effect on Intact Animals 



In the intact frog, aneurine produced central motor and respiratory 

 paralysis and pupillary constriction. In mice, small doses stimulated 

 respiration, whilst large doses produced chronic cramps and respiratory 

 arrest. In rabbits, intravenous injection of 0-05 to i mg. stimulated 

 respiration and raised the blood pressure.^ Aneurine did not increase 

 the purgative effect of phenolphthalein in monkeys. ^^ 



The toxic symptoms observed in rabbits were : * peripheral 

 vasodilatation, decreased respiration due to a direct action on the 

 respiratory centre in the medulla, asphyxial convulsions due to anoxia 

 resulting from decreased oxygenation of the blood, death by paralysis 

 of the respiratory centre and cardiac arrhythmias, probably due to 

 anoxia and not to a direct action on the cardiac muscle of the con- 

 duction system. In dogs, intravenous injection of aneurine hydro- 

 chloride solution caused a marked but transient fall in blood pressure, 

 bradycardia, transitory vasodilatation and transitory changes in the 

 electrocardiogram ; death was due to respiratory arrest. ^^<* 



When applied directly to the cerebral cortex, aneurine produced 

 motor reactions, consisting of rhythmic contractions of the muscle 

 corresponding to the cortical " motor " point at which it was applied. ^^ 

 The reaction was at first weak, but subsequently increased in intensity. 

 When all the skeletal musculature was involved, generalised epilepti- 

 form convulsions took place with a tonic-clonic sequence. Epilepti- 

 form convulsions were produced in thirty-four out of forty-five dogs 

 by means of a 2 to 10 % solution applied in this way, but in eleven of 

 the dogs only localised muscular clonic reactions could be obtained. 

 Identical results were obtained with cocarboxylase, but the pyrimidine 

 and thiazole halves of the molecule had no effect. 



Relation between Aneurine and Acetyl Choline 



An association of a different type between aneurine and acetyl 

 choline was indicated by Kuhn et al.^^ Like choline, aneurine is a 

 quaternary ammonium base and a primary alcohol, and its acetyl 

 derivative was found to behave like acetyl choline in stimulating the 



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