Supplementary studies on pharmacology of EDTA

Toyota H, Shibata S (Kyoto University). Supplementary studies on pharmacology of disodium ethylenediaminetetraacetate (EDTA salt). Nippon Yakuriguku Zasshi. 1956;52:1-9. (CA51:11567e) [The L.D.50 in mice of EDTA salt was 20.5 mg./kg. orally and 2.6 mg./kg. intraperitoneally. The toxic symptoms were described. The coagulation of 0.9 cc. of normal human blood was completely inhibited by 0.1 cc. of 0.0145M EDTA salt, but it was not by 0.1 cc. of 0.014M EDTA salt. The limiting concn. of ammonium oxalate for the anticoagulation was 0.032M and that of Na citrate was 0.050M The action of EDTA salt was suggested as forming a complex with Ca in blood, not only of ionic form but also of bound form, the latter of which was interpreted to be a key substance in the blood coagulation. The data with ammonium oxalate and Na citrate support this view. The inhibition of the coagulation was also achieved by a combination of 0.22 cc. 0.014M EDTA salt and 0.1 cc. 0.014M CaCl2, and also the combination of 0.1 cc. 0.042M ammonium oxalate and 0.1 cc. 0.01M CaCl2 and that of 0.1 cc. 0.12M Na citrate and 0.1 cc. 0.02M CaCl2. Expts. with thromboplastin showed a similar result with EDTA salt, but higher limiting concns. for ammonium oxalate and Na citrate. EDTA salt had less influence on the red corpuscle pptn. velocity than did ammonium oxalate and Na citrate. The motility of the isolated rabbit auricle was inhibited by 0.3 cc. but not by smaller vols. of 2% EDTA salt. The inhibited motility was recovered by administration of 0.3 cc. 2% CaCl2. In some cases, CaCl2 in equiv. doses did not restore the original motility. The inhibition by EDTA salt was also observed when Ca-deficient Ringer soln. was employed as the perfusant, and in this case administration of CaCl2 resulted in larger motility than the original one. These results suggest that the motility inhibition by EDTA salt is not due only to trapping the Ca ion. The isolated sinoauricular prepn. of toad was also inhibited by EDTA salt and also by other Ca-combining compds. The inhibition was not removed by atropine and had no relation with the action of hexamethonium or nicotine. The nerve-muscles of frog lost the responding ability toward indirect stimulus by soaking in the Ringer soln. contg. EDTA salt. The E.D.50 was 2.53 mg./10 cc. The responses toward direct stimulus were not lost. The E.D.50 was approx. 7 times as large a concn. as needed to trap Ca in the soaking soln. Addn. of a certain amt. of Ca recovered the response of soaked muscle toward indirect stimulus. The nerve-muscle did not lose the response ability toward elec. stimulus when soaked in Ca-deficient Ringer soln. EDTA salt in various concns. had no significant effect on the isolated ear vein of rabbit by perfusion

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