Newer antihistaminics: III. Some pharmacologic and therapeutic effects of β-(P-methylbenzhydryloxy)-ethyldimethylamine hydrochloride, a derivative of diphenhydramine hydrochloride

Abstract 1.1. One hundred thirty-one normal subjects and some of 205 patients have been subjected to extensive clinical study while receiving β-(p-methyl-benzhydryloxy)-ethyldimethylamine hydrochloride (Toladryl). Among the positive effects observed were: 1.1.(A) Suppression of the dermal response to histamine in all of 30 subjects studied. 1.2.(B) A mild atropine-like action upon the eye in 40 of 60 subjects following the topical application of the drug in a 0.5 per cent aqueous solution. 1.3.(C) An improvement in glucose tolerance following the prolonged uses of large doses of Toladryl (450 mg. daily for from one to 4 weeks) in 8 of 11 patients. 1.4.(D) A significant lowering of the basal metabolic rate in 19 of 26 subjects who ingested 300 and 450 mg., respectively, for periods of not less than one week each. 2.2. In daily doses varying from 75 to 600 mg. ingested for periods of time varying from one to 80 weeks no appreciable changes were produced by Toladryl in the following: weight, water balance, pulse rate, blood pressure, electrocardiogram, a variety of fasting blood chemical determinations, the blood count, sedimentation rate of erythrocytes, and urinalysis. 3.3. Two hundred five patients have received Toladryl over periods of time varying from one day to 80 weeks. Either partial or complete relief was afforded all cases of acute urticaria, angioneurotic edema, and generalized pruritus. More than 85 per cent of the cases of seasonal hay fever were relieved. About 80 per cent of the cases with chronic urticaria and nonseasonal allergic rhinitis were improved, while 70 per cent of the asthmatics were helped in major or minor degree. Among the miscellaneous conditions, in which results of treatment were still less satisfactory, must be included migraine, hypertension, contact dermatitis, spastic colitis, and functional dysmenorrhea. 4.4. Therapeutically effective amounts of Toladryl varied from unit doses of 25 mg. (e.g., in migraine) to daily doses of 300 mg. (e.g., in acute urticaria). Maintenance doses of the drug have varied from 50 to 200 mg. daily. 5.5. The histamine-blocking effect of Toladryl may become manifest within 20 to 30 minutes after the first dose is given, but clinical improvement may lag considerably, as in asthma, for, like all other compounds of its class, Toladryl is not capable of reversing or altering the influence of the histamine which has already attached itself to the responding cells or system. 6.6. In 222 subjects, the over-all incidence of side effects or untoward reactions was 15.8 per cent. No such reactions were observed with daily doses below 100 mg. Qualitatively, these "toxic" symptoms resembled those caused by diphenhydramine hydrochloride, but occurred much less often and were rarely as pronounced. In the descending order of frequency, the most commonly noted were drowsiness, dryness of the mouth and throat, dizziness, tiredness, and vague abdominal complaints. In only 4 of our subjects were these manifestations sufficiently severe to necessitate either a decrease in dose or a cessation of administration. In 2 of these, these side effects became intolerable only when 450 and 600 mg., respectively, were employed daily for a week or more.