386 



Prof. J. T. Cash and Mr. W. R Dunstan. 



introducton of methyl into the molecule of an alkaloid. Methyl benz- 

 aconine is however more toxic and generally more powerful than 

 benzaconine, owing to the presence of the methyl group. 



Action of Pyraconitine. 



The main effects of pyraconitine may be thus summarised. Its 

 local application is devoid of the effects characteristic of the acoivi- 

 tines. Its chief action upon the heart is to cause slowing, partly 

 from vagus irritation, partly from depression in function of intrinsic 

 rhythmical and motor mechanisms. 



There is less tendency to want of sequence in the cardiac chamber 

 walls than is observed after the aconitines and benzaconine. 



The vagus apparatus remains active in degree after doses some- 

 what in excess of the lethal, the slowed heart of pyraconitine being 

 accelerated both by vagotomy and by atropine. 



Activity of respiration is reduced (by central depression) to a degree 

 incompatible with life, as is the case after aconitine and benzaconine. 

 The peripheral motor nerves and muscular tissues are not at this time 

 markedly affected. Artificial respiration prolongs life, but the slowed 

 heart and greatly reduced blood pressure tend to a fatal issue. 



The spinal cord is impaired in its reflex function, apparently 

 secondarily to reduced circulation in its structure. A tendency to 

 tonic spasm in frogs is late in appearing and of moderate degree. It 

 has not been seen after destruction of brain and medulla. It is 

 further associated with a curious condition of exaggerated motility. 



Neither muscular nor intramuscular nervous tissue are strongly 

 influenced by pyraconitine in lethal or somewhat hyperlethal doses. 

 The lethal dose per kilo, frog's weight is practically about twelve times 

 that which is lethal per kilo, rabbit's weight. 



Contrasted Effects of Pyraconitine and Benzaconine. 



Of these two alkaloids, pyraconitine is approximately six to seven 

 times more toxic towards mammals (rabbits and guinea-pigs) than 

 benzaconine, and five to six times more so towards frogs. They are 

 alike in their action upon mammals, in so far as they are non-irritant, 

 that they slow the respiration without preliminary acceleration, that 

 they slow the heart and reduce the blood pressure to a very low level, 

 that they cause paresis and in guinea-pigs clonic movements, and 

 that respiratory failure is the immediate cause of death. They differ 

 in so far that pyraconitine acts more rapidly, but for a shorter period, 

 whilst fatal termination of poisoning is preceded by convulsions, 

 which are very rare after benzaconine. Benzaconine alters the 

 sequence of the ventricles upon the auricles much more usually and 



