RT Journal Article
SR Electronic
T1 THE TOXICOLOGIC PROPERTIES OF N,N-DIMETHYL-N'-(3-THENYL)-N'-(2-PYRIDYL) ETHYLENEDIAMINE HYDROCHLORIDE (THENFADIL): A NEW ANTIHISTAMINIC DRUG
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 371
OP 378
VO 97
IS 3
A1 JAMES O. HOPPE
A1 A. M. LANDS
YR 1949
UL http://jpet.aspetjournals.org/content/97/3/371.abstract
AB 1. The acute intravenous toxicity of WIN 2848 was found to be similar to that of tripelennamine in mice, rats and rabbits, but significantly greater in hamsters. Both compounds were more toxic than diphenhydramine by intravenous, subcutaneous and intraperitoneal injection in mice. The acute oral toxicity of WIN 2848 in mice was similar to that of tripelennamine and diphenhydramine. 2. When administered subcutaneously to rats once daily, six days a week for three weeks, WIN 2848 caused no deaths at 5 and 10 mgm./kgm., one death at 20 mgm./kgm. after nineteen days of medication and killed all of the test animals by the twentieth day at 40 mgm./kgm. No significant effect on body weight was encountered at doses of 5, 10 and 20 mgm./kgm. No significant hematologic or pathologic changes were found. 3. WIN 2848 administered orally to dogs in doses of 5 and 10 mgm./kgm. once daily, six days a week for 90 days resulted in no deaths or loss in body weight. No significant changes were observed in hematology, blood glucose, non-protein nitrogen, blood chloride, albumin, globulin or total protein values. No tissue changes were found which could be attributed to the drug. 4. No signs of intoxication were observed upon repeated administration of 5 mgm./kgm. either subcutaneously in rats for three weeks or orally in dogs for three months. Evidence of cumulative toxicity was observed at doses of 10 and 20 mgm./kgm. upon subcutaneous administration in rats. 5. No evidence of cumulative toxicity was observed with oral medication in dogs at doses of 5 and 10 mgm./kgm. 6. The signs of acute intoxication with WIN 2848 were, in general, similar to those of known, commercially available antihistaminic drugs. 7. The mean waking time of mice from Evipal-induced sleep was prolonged 8 per cent by WIN 2848, 11 per cent by tripelennamine and 43 per cent by diphenhydramine. 1949 by The American Society for Pharmacology and Experimental Therapeutics