Alles, Gordon A. (1926) The comparative physiological action of some derivatives of guanidine. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-11022004-113158
Guanidine, methylguanidine and asymmetric dimethylguanidine are of extended biological interest. Guanidine itself has been isolated as a nitrogenous constituent of some plants, [1,2] while methyl and dimethyl guanidine probably play a part in intermediary nitrogen metabolism and have been isolated as physiological constituents in the urine of the dog, horse and man. [3,4,5]
Pathologically these compounds have considerable interest from many points of view. Koch  found methylguanidine in the urine of parathyroidectomized dogs and later reported the presence of guanidine, symmetric and asymmetric dimethylguanidine, choline, neurine and histamine.  Henderson  reports that with such dogs there is a decreased muscular content of substances containing guanidine complex. Burns and Sharpe  carefully determined the guanidine and methylguanidine in the blood of animals after parathyroidectomy and found a marked increase of these substances, together with an increase of these bases in the urine, as had been reported by Koch. Paton and Findlay  showed that the symptoms of tetania parathyreopriva are identical with those produced by the administration of guanidine and methylguanidine, and Watanabe  has shown that the injection of guanidine causes hypoglucemia, calcium decrease in the blood, phosphate retention and acidosis similar to the metabolic changes occurring after parathyroidectomy. Burns and Sharpe  found an increased content of guanidine and methylguanidine in the urine of children with idiopathic tetany and Findlay and Sharpe  and Nattrass and Sharpe  found an increased excretion of dimethylguanidine. Methylguanidine has been isolated from the faeces of children with idiopathic tetany.
Major  believes that there is a possible relationship between metabolism and hypertension in man. Fairly large quantities of methylguanidine are reported to occur in the urine of animals killed by anaphylactic shock or by burning, according to Heyde [16,17] and it has been suggested that the poison produced by shock may be the methylguanidine elaborated by the toxicogenic destruction of protein. Heyde reported  that methylguanidine poisoning in gunea-pigs and rabbits showed a marked similarity to anaphylactic shock, but Fühner  using rabbits and Loewitt  using guinea-pigs were not able to observe any marked lung action when using a synthetic methylguanidine.
Guanidine and especially methylguanidine have been shown to be active in decreasing the poisonous action of protein split-products by Weichardt and Schwenk.  Similar to this is the observation of Burns that methylguanidine protects sensitized animals from toxic doses of antigenic protein. The possible relationship of the guanidines to epilepsy, epidemic encephalitis and various protein intoxications has been discussed in the literature.
Because of the widespread interest regarding the physiological activity of guanidine, its methyl and asymmetric dimethyl derivatives, it seemed that a study of the relation between chemical constitution and certain physiological actions of several guanidine derivatives would be desirable. Pharmacological studies have been made by previous workers with the following derivatives [22,23]; guanidine, methylguanidine, asymmetric dimethylguanidine, dicyandiamidine, glycocyamine, creatine and agmatine. These studies in the case of guanidine, methylguanidine and dimethylguanidine have fairly completely covered their general physiological action, but little attempt has been made to carefully compare their relative physiological activity. For the study of the derivatives prepared in this work it was decided that careful observations of their blood pressure and respiratory effects, together with toxicity determinations would offer the best comparisons of their relative physiological activity.
The glucemic effect of these derivatives was also investigated as it seemed probable that a variation in chemical constitution might produce a substance having a hypoglucemic activity much greater than that of guanidine itself.  Such a fact would be of considerable importance with regard to speculations concerning a possible chemical constitution of insulin.
|Item Type:||Thesis (Dissertation (Ph.D.))|
|Degree Grantor:||California Institute of Technology|
|Division:||Chemistry and Chemical Engineering|
|Thesis Availability:||Public (worldwide access)|
|Defense Date:||1 January 1926|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Imported from ETD-db|
|Deposited On:||02 Nov 2004|
|Last Modified:||26 Dec 2012 03:07|
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