THE TOXICOLOGIC AND ANTIHISTAMINIC PROPERTIES OF N,N'-DIMETHYL-N'-PHENYL-N'-(2-THIENYLMETHYL) ETHYLENE-DIAMINE HYDROCHLORIDE (DIATRIN)

¹ Department of Pharmacology and Chemotherapy, Warner Institute for Therapeutic Research, New York 11, N. Y.

N,N'-dimethyl-N'-phenyl-N'-(2-thienylmethyl) ethylenediamine hydrochloride (Diatrin) has been studied for its antihistaminic and toxicological properties. The following findings are reported:

(1) Doses of 0.1-1.0 /cc inhibit the contraction induced by histamine in the isolated intestine and uterus of guinea pigs. The effect of 20-50 histamine on the perfused lung is inhibited by 0.5-1.0 mg Diatrin.

(2) Injected intravenously into dogs, Diatrin interferes with the blood pressure lowering effect of successive histamine injections.

(3) It protects guinea pigs against lethal histamine asthma in doses of 0.05 mg/kg (subcut.).

(4) It protects guinea pigs against multiple lethal doses of intravenous histamine. The minimal active dose against 2-5 lethal doses is 0.25-0.50 mg/kg.

(5) It protects horse-serum sensitized guinea pigs against lethal anaphylactic shock in 0.5 to 1.0 mg/kg doses.

(6) The therapeutic index of Diatrin is high, particularly by the oral route of administration (300-1200); by subcutaneous administration the index is 80 in anaphylaxis, 800 in histamine asthma.

(7) From a qualitative standpoint, the pharmacological action of the drug is similar to that of other antihistaminics of the ethylenediamine series.

(8) The comparative evaluation of toxic, convulsive, and lethal doses in mice, rats, guinea pigs, rabbits, dogs and cats, indicates that the compound is characterized by a high tolerance. Histopathologic studies confirm this finding.

(9) There is no relationship between the anti-histamine and antianaphylactic effectiveness of various antihistaminic preparations. Similarly, the doses protecting against inhaled and injected histamine, or giving protection in vitro, do not necessarily have the same relationship in different compounds.