388 The Pharmacology of Pyraconihne and Methylbenzaconine. 



a certain stage of the action of metkylbenzaconine, especially upon 

 guinea-pigs) are suggestive of the action of a near ally of aconitine. 

 In frogs, however, there is no semblance to an aconitine effect, unless 

 its very feeble action towards sensory nerves or its much more 

 powerful action upon motor nerves, be thus viewed. Motor nerves 

 are greatly affected by doses which are distinctly below the lethal for 

 cold-blooded animals, the action being curare-like in character. Mus- 

 cular tissue is after the action of large doses more susceptible of 

 fatiguing influences. Fibrillation in muscles to which the poison has 

 access is more common than after aconitine or any other derivative 

 examined. 



These observations support in the main the contention of Cruni 

 Brown with Fraser that the introduction of methyl into the molecule 

 of certain spasm-producing alkaloids, marks the effect of these by 

 occasioning a curare-like action at the periphery. 



Contrasted Effects of Metlujlhenzaconine and Aconitine. 



The toxicity of aconitine is, roughly, eighty to one hundred times 

 that of methylbenzaconine towards rabbits and guinea-pigs, and much 

 the same proportion holds for summer and winter frogs respectively. 

 Whilst slight tendency to salivation and retching movements are pro- 

 duced by methylbenzaconine, and are in so far suggestive of a slight 

 aconitine action, the absence of initial acceleration of respiration, of 

 local irritation, and dyspnoeal convulsions, and the predominance of 

 paralytic symptoms, are points of difference. The action upon the 

 heart is entirely distinct, for the pulse is slowed by methylbenz- 

 aconine, the auricles eventually beating more rapidly than the ventri- 

 cles, the action of the poison proceeds uniformly and without the 

 intermissions which characterises aconitine, whilst the early phenomena 

 of vagus stimulation have little in common. The general symptoms 

 of poisoning in frogs have scarcely a point of similarity, quiescence, 

 rapid failure of reflex, and voluntary movement, without impairment 

 of the cardiac action, are distinctive of methylbenzaconine, whilst 

 excitement with great motility and persistence of voluntary move- 

 ment follow aconitine. Fibrillation is much more pronounced after 

 the former, though it is only a transitory phenomenon. The action 

 on the heart differs widely in frogs as it does in mammals, whilst the 

 curare-like action of the derivative on motor nerves is not produced by 

 aconitine in doses which just suffice to arrest the heart. 



It is true that large but sublethal doses of aconitine are followed by 

 a condition of almost complete paralysis, which lasts for several days, 

 but during this time there is slight voluntary and reflex movement, the 

 nerve-endings are not put out of action, and the circulation is usually 

 of the feeblest character, all conditions which are not found in the 

 period of quiescence following methylbenzaconine. 



