Parasympatholytic Drugs 81 



Emmelin, Muren and Stromblad (1954); Wills and Somers (1956); 

 Stromblad (1957/;); Emmelin and Stromblad (1958). 



PARASYMPATHOLYTIC DRUGS 



It has already been emphasized that salivary secretion (caused 

 by parasympathetic impulses or parasympathomimetic drugs) is 

 easily blocked by atropine. Several investigators have found secre- 

 tion of saliva, usually induced by injection of pilocarpine or car- 

 bachol, to be a convenient test for the assay of atropine-like drugs 

 (Cushny, 1920; Nyman, 1942; Bulbring and Dawes, 1945; Brown 

 and Quinton, 1957). In the low concentrations required to an- 

 tagonize such secretion atropine has a specific parasympatholytic 

 effect and ever since the discovery of its antisialogogue action 

 (Heidenhain, 1872) it has been a useful tool in physiological and 

 pharmacological experiments on salivary secretion. It has, however, 

 certain drawbacks when used for such purposes. When the dose is 

 increased, the specificity of action is lost. Long ago, Langley (1878) 

 found that atropine could prevent the sympathetic from producing 

 a flow of saliva when the nerve was stimulated proximal to the 

 superior cervical ganglion, whereas postganglionic sympathetic 

 stimulation still caused secretion ; but even such stimulation became 

 ineffective if the dose of atropine was further raised. Similar obser- 

 vations were made by Carlson (1907). Atropine has apparently a 

 ganglionic blocking action which has been analysed by Konzett 

 and Rothlin (1953). In addition it has a more peripheral, sym- 

 pathetic blocking action in high concentration, abolishing the 

 secretory effect of postganglionic stimulation or injection of 

 adrenaline. 



It may further be pointed out that atropine is less well suited 

 for chronic experiments because of the pronounced tolerance which 

 develops to this drug. This phenomenon may be illustrated on 

 salivary secretion in the following way. When a parasympatholytic 

 agent is administered repeatedly to a cat over a period of some 

 weeks, a supersensitivity to adrenaline develops in the submaxil- 

 lary gland, resembling that seen after section of the chorda; if 

 atropine is used as a blocking agent the dose has to be increased 

 successively (Emmelin and Muren, 1950ft). If the same small dose 

 of atropine is given for some weeks, the sensitivity first increases, 

 but then decreases again almost to the pre-treatment level (Em- 

 melin and Macintosh, 1955). 

 p.s.g. — G 



