EVIDENCE FOR THE INVOLVEMENT OF HISTAMINE IN THE ANTIDYSTONIC EFFECTSOF DIPHENHYDRAMINE

Although diphenhydramine hydrochloride is known to eliminate or reduce the symptoms of dystonia in human patients with acute dystonic reacti ons and idiopathic torsion dystonia, its mechanism of action is still unclear. In the present study, we show that the antihistamine properti es of diphenhydramine may contribute to its beneficial effects. Acute dystonic reactions were produced in rats with unilateral microinjectio n of haloperidol into the red nucleus as previously described. Similar to the pattern in humans, this effect could be attenuated by coadmini stration of diphenhydramine. Unilateral microinjection of histamine it self into the rat red nucleus produced dystonic postures (torticollis) in a dose-dependent manner, demonstrating that a histamine dysfunctio n could contribute to the pathophysiology of dystonia. The torticollis produced by histamine could be significantly attenuated with coadmini stration of the H1 antagonists diphenhydramine or pyrilamine or the H2 antagonist cimetidine. These effects are thought to be mediated throu gh the red nucleus because significantly more torticollis was observed when histamine was injected into the red nucleus rather than surround ing midbrain areas, the substantia nigra, or the lateral ventricle. Th e present data, taken together with studies in humans, suggest the inv olvement of histamine in some types of dystonia. Furthermore, the red nucleus and related motor pathways may have a more important role in d ystonia than previously thought. (C) 1995 Academic Press, Inc.