Antihistaminics in Idiopathic Dystonia

I read with interest the article by Truong et al¹ describing a beneficial effect of diphenhydramine hydrochloride in 3 of 5 consecutive patients with idiopathic dystonia. The mechanism of action of diphenhydramine in these patients remains uncertain and the authors mention the possibility of anticholinergic effects (suggested as unlikely), histamine₁-antagonist effects, and potential interactions with opiates. I should like to draw readers' attention to a study that we published in 1982² evaluating the short-term effects of parenteral injections of 2 drugs with anticholingeric properties: benztropine mesylate (with potent central antimuscarinic properties and a high capacity to block dopamine reuptake), and atropine sulfate (a classic anticholinergic lacking effects on dopamine reuptake) as well as chlorpheniramine maleate, a potent antihistaminic with less anticholinergic properties than benztropine and diphenhydramine. We studied the effects of single parenteral injections of the 3 drugs compared with normal saline placebo in a randomized