Jaw S P, Nguyen B, Vuong Q T, Trinh T A, Nguyen M, Truong D D
Department of Neurology, University of California, Irvine 92717, USA.
Brain Res Bull. 1996;39(3):189-92. doi: 10.1016/0361-9230(95)02103-5.
Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac arrest and resuscitation. Previous results showed that dysfunction of central GABAergic neurotransmission may contribute to the disease. In current studies, effects of GABA uptake inhibitors, guvacine hydrochloride (1,2,5,6-tetrahydro-3-pyridine carboxylic acid hydrochloride) and (+/-)-cis-4-hydroxynipecotic acid ([+/-]-cis-4-hydroxy-3-piperidine carboxylic acid), in the pathophysiology of posthypoxic myoclonus were investigated. Administration of guvacine (1 or 10 mg/kg, IP) or nipecotic acid (0.5 or 5 mg/kg, IP) significantly attenuated myoclonus scores of the animals. Tolerance to antimyoclonus effects of these two compounds did not develop after chronic administration (twice a day for 14 days) of guvacine (10 mg/kg, IP) or nipecotic acid (5 mg/kg, IP). On the other hand, tolerance was noticed with clonazepam (2.5 mg/kg, IP twice a day for 7 days). The results indicate that guvacine or nipecotic acid may be used in combination with (at reduced doses) or as alternatives to clonazepam to treat patients with the disease so as to reduce tolerance phenomenon usually associated with clonazepam.
雄性Sprague-Dawley大鼠在经历10分钟心脏骤停及复苏后出现了缺氧后肌阵挛。先前的研究结果表明，中枢γ-氨基丁酸能神经传递功能障碍可能与该疾病有关。在当前的研究中，研究了γ-氨基丁酸摄取抑制剂盐酸胍可辛（1,2,5,6-四氢-3-吡啶羧酸盐酸盐）和（±）-顺式-4-羟基尼克酸（（±）-顺式-4-羟基-3-哌啶羧酸）在缺氧后肌阵挛病理生理学中的作用。给予胍可辛（1或10毫克/千克，腹腔注射）或尼克酸（0.5或5毫克/千克，腹腔注射）可显著降低动物的肌阵挛评分。在慢性给予胍可辛（10毫克/千克，腹腔注射，每天两次，共14天）或尼克酸（5毫克/千克，腹腔注射，每天两次，共14天）后，并未产生对这两种化合物抗肌阵挛作用的耐受性。另一方面，氯硝西泮（2.5毫克/千克，腹腔注射，每天两次，共7天）则出现了耐受性。结果表明，胍可辛或尼克酸可与氯硝西泮联合使用（降低剂量）或作为其替代品用于治疗该疾病的患者，以减少通常与氯硝西泮相关的耐受性现象。
