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II. — Studies on the Pharmacological Action of Tetra-Alkyl-Ammonium 

 Compounds. By Professor 0. R. Marshall. 



(MS. received April 30, 1913. Read November 17, 1913. Issued separately December 29, 1913.) 



I. THE ACTION OF TETRA-METHYL-AMMONIUM CHLORIDE. 



In a paper on " The Pharmacological Action of Protocatechyl-tropeine," communi- 

 cated to the Society in 1909, # I drew attention to the fact that this substance, when 

 injected intravenously in certain doses produces transient paralysis of the respira- 

 tion ; and I mentioned further that Tappeiner t had described a similar temporary 

 cessation of the respiration after the intravenous injection of certain quaternary 

 isoxazol and pyrazol compounds, and of tetra-methyl-ammonium chloride, and Pohl,} 

 after the intravenous injection of some quaternary papaverine derivatives. Tappeiner 

 came to the conclusion that the effect was due to stimulation of the terminations 

 of the fifth cranial nerve in the nose ; that it was, in fact, of the nature of a 

 Kratschmer-Hering reflex, since he was unable, in the case of methyl-phenyl- 

 isoxazol-methochloride, to produce cessation of the respiration after anaesthetising 

 the nasal mucous membrane with cocaine ; and Iodlbauer,§ working in Tappeiner's 

 laboratory, also found that ansesthetisation of the nasal mucous membrane prevented 

 the cessation of the respiration produced by tetra-methyl-ammonium chloride. Pohl, 

 on the other hand, was able to produce this temporary paralysis of the respiration 

 after section of the ophthalmic branches of both fifth nerves, and consequently he 

 concluded that the effect was due to an action on the respiratory centre. I came 

 to the same conclusion, since the effect was still obtained with protocatechyl-tropeine 

 after section of both fifth nerves in the base of the skull and after section of both 

 phrenic nerves, and was not synchronous with the effect on the circulation or with 

 the paresis of the nerve-endings in the muscles of the hind limbs. Further work 

 with tetra-methyl-ammonium chloride, however — my stock of protocatechyl-tropeine 

 being exhausted, — showed that the effect was in large measure peripheral and due 

 to a transient paresis of the nerve-endings in the respiratory muscles. 



Action on Motor Nerve- Endings. 



The effect of tetra-methyl-ammonium compounds on the motor nerves was first 

 observed by Crum Brown and Fraser.|| They showed that the iodide when injected 

 into frogs produced muscular paralysis due to an action on the myo-neural junctions ; 



* Trans., xlvii., pt. ii. p. 273 [1909-10]. t Arch.f. exp. Path. u. Pharm., xxxvii. p. 325 [1896], 



% Arch. Internat. de Pharmacod., xiii. p. 479 [1904]. § Arch. Internat. de Pharmacod., vii. p. 183 [1900]. 

 || Proc. Boy. Soc. Edin., vi. p. 556 [1869]. 



TRANS. ROY. SOC. EDIN., VOL. L. PART I. (NO. 2). 3 



