van't Groenewout J L, Stone M R, Vo V N, Truong D D, Matsumoto R R
Department of Neurology, University of California at Irvine 92717, USA.
Exp Neurol. 1995 Aug;134(2):253-60. doi: 10.1006/exnr.1995.1055.
Although diphenhydramine hydrochloride is known to eliminate or reduce the symptoms of dystonia in human patients with acute dystonic reactions and idiopathic torsion dystonia, its mechanism of action is still unclear. In the present study, we show that the antihistamine properties of diphenhydramine may contribute to its beneficial effects. Acute dystonic reactions were produced in rats with unilateral microinjection of haloperidol into the red nucleus as previously described. Similar to the pattern in humans, this effect could be attenuated by coadministration of diphenhydramine. Unilateral microinjection of histamine itself into the rat red nucleus produced dystonic postures (torticollis) in a dose-dependent manner, demonstrating that a histamine dysfunction could contribute to the pathophysiology of dystonia. The torticollis produced by histamine could be significantly attenuated with coadministration of the H1 antagonists diphenhydramine or pyrilamine or the H2 antagonist cimetidine. These effects are thought to be mediated through the red nucleus because significantly more torticollis was observed when histamine was injected into the red nucleus rather than surrounding mid-brain areas, the substantia nigra, or the lateral ventricle. The present data, taken together with studies in humans, suggest the involvement of histamine in some types of dystonia. Furthermore, the red nucleus and related motor pathways may have a more important role in dystonia than previously thought.
尽管已知盐酸苯海拉明可消除或减轻急性肌张力障碍反应和特发性扭转性肌张力障碍患者的肌张力障碍症状，但其作用机制仍不清楚。在本研究中，我们表明苯海拉明的抗组胺特性可能有助于其产生有益效果。如前所述，通过向大鼠红核单侧微量注射氟哌啶醇来诱发急性肌张力障碍反应。与人类的情况类似，联合使用苯海拉明可减轻这种效应。向大鼠红核单侧微量注射组胺本身会以剂量依赖性方式产生肌张力障碍姿势（斜颈），表明组胺功能障碍可能参与了肌张力障碍的病理生理过程。联合使用H1拮抗剂苯海拉明或吡苄明或H2拮抗剂西咪替丁可显著减轻组胺引起的斜颈。这些效应被认为是通过红核介导的，因为当将组胺注射到红核而不是周围的中脑区域、黑质或侧脑室时，观察到的斜颈明显更多。目前的数据与在人类中的研究一起表明，组胺参与了某些类型的肌张力障碍。此外，红核和相关的运动通路在肌张力障碍中可能比以前认为的具有更重要的作用。
