Ell J, Gresty M
J Neurol Neurosurg Psychiatry. 1983 Aug;46(8):716-24. doi: 10.1136/jnnp.46.8.716.
The effects of the "vestibular sedative" drug Flunarizine upon the oculomotor functions of pursuit and voluntary saccades and upon the vestibular response (to rotational stimuli) were assessed in twenty volunteer subjects. The study was then extended to three patients with chronic imbalance of central origin who had reported a beneficial symptomatic response to the drug. Three of the volunteer subjects were found to have a directional preponderance (presumed to arise from peripheral dysfunction). In the remaining seventeen normal subjects Flunarizine was found to reduce the amplitudes of fast phases of vestibular nystagmus. The directional preponderance in the other three subjects was redressed through production of fast phases which were of lower and more uniform amplitude. In the patients, in addition to a reduction in fast phase amplitude, there was a reduction or abolition of after nystagmus. In no case was any reduction in slow phase velocity observed. Pursuit and voluntary saccades were unaffected by the drug. It was concluded, on the basis that the fast phases of nystagmus are centrally generated, that Flunarizine has a central action rather than a depressant effect upon the vestibular end organ. In view of known oculomotor physiology and pharmacology it is proposed that vestibular sedatives act by depression of Type II vestibular neurons, and modification of the functional relationships between the vestibular nuclei, the perihypoglossal nuclei and the flocculus of the cerebellum. A trial of vestibular active drug is indicated particularly in patients in whom asymmetry of the vestibular response and/or abnormal after nystagmus is demonstrated.
在20名志愿者身上评估了“前庭镇静剂”氟桂利嗪对跟踪和随意扫视的动眼功能以及前庭反应(对旋转刺激)的影响。该研究随后扩展到3名患有中枢性慢性失衡的患者,他们报告称该药物有有益的症状缓解作用。发现3名志愿者受试者存在方向优势(推测源于外周功能障碍)。在其余17名正常受试者中,发现氟桂利嗪可降低前庭眼震快相的幅度。另外3名受试者的方向优势通过产生幅度更低且更均匀的快相得到纠正。在这些患者中,除了快相幅度降低外,还出现了眼震后效降低或消失的情况。在任何情况下均未观察到慢相速度降低。跟踪和随意扫视不受该药物影响。基于眼震快相是由中枢产生的这一事实得出结论,氟桂利嗪具有中枢作用而非对前庭终器的抑制作用。鉴于已知的动眼生理学和药理学知识,有人提出前庭镇静剂通过抑制II型前庭神经元以及改变前庭核、舌下神经周围核和小脑绒球之间的功能关系来发挥作用。特别是在前庭反应不对称和/或眼震后效异常的患者中,建议试用前庭活性药物。