Extracellular Concentrations of Dopamine and Metabolites in the Rat Caudate After Oral Administration of a Novel Catechol-O-Methyltransferase Inhibitor Ro 40–7592

The effect of the systemic administration of a novel, orally active, catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592, on the in vivo extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was studied by transcerebral microdialysis in the dorsal caudate of freely moving rats. Ro 40-7592 (at doses of 3.0, 7.5, and 30 mg/kg p.o.) elicited a marked and long-lasting reduction of HVA, and at doses of 7.5 and 30 mg/kg, an increase of DOPAC output, but it failed to increase DA output. The administration of L-beta-3,4-dihydroxyphenylalanine (L-DOPA, 20 and 50 mg/kg p.o.) with a DOPA decarboxylase inhibitor (benserazide) increased both HVA and DOPAC output, but failed to modify significantly extracellular DA concentrations in dialysates; in contrast, combined administration of L-DOPA+benserazide with Ro 40-7592 (30 mg/kg p.o.) resulted in a significant increase in DA output. Ro 40-7592 prevented the L-DOPA-induced increase in HVA output and markedly potentiated the increase in DOPAC output. To investigate to what extent the increase in extracellular DA concentrations was related to an exocitotic release, tetrodotoxin (TTX) sensitivity was tested. Addition of TTX to Ringer, although abolishing DA output in the absence of L-DOPA, partially reduced it in the presence of L-DOPA+Ro 40-7592 and even more so after L-DOPA without the COMT inhibitor. The results of the present study suggest that metabolism through COMT regulates extracellular concentrations of DA formed from exogenously administered L-DOPA but not of endogenous DA.(ABSTRACT TRUNCATED AT 250 WORDS)     

阿托伐他汀钙对帕金森病细胞模型的保护作用及其临床意义

目的:评价阿托伐他汀钙对帕金森病细胞模型及帕金森病患者临床症状的影响。方法:首先使用MPP+处理SH-SY5Y细胞建立帕金森病细胞模型。观察阿托伐他汀钙在该模型中对Wnt通路以及细胞凋亡的影响。其次选取66例符合纳入标准的临床患者,其中33例服用多巴丝肼片和盐酸普拉克索(普通治疗组)。其余33例则因其他原因在使用多巴丝肼片和盐酸普拉克索治疗期间服用阿托伐他汀钙片(阿托伐他汀组)。观察两组患者的Hoehn-Yahr分级,UPDRS评分,以及不良反应的发生率。结果:在MPP+处理组,Wnt通路受到抑制且细胞发生凋亡,而阿托伐他汀钙预处理可缓解MPP+引起的Wnt通路的抑制和细胞凋亡,差异具有统计学意义(P0.05)。治疗8周后阿托伐他汀组的Hoehn-Yahr分级改善情况显著优于普通治疗组的改善情况,并且差异具有统计学意义(P0.05);治疗8周后普通治疗组的UPDRS评分高于阿托伐他汀组的评分,差异具有统计学意义(P0.05);阿托伐他汀组的不良反应发生率低于普通治疗组,但差异无统计学意义(P0.05)。结论:阿托伐他汀钙可通过Wnt通路保护MPP+引起的细胞凋亡并且在临床治疗中能较好的改善帕金森病患者的运动和非运动症状。     

苄丝肼微球的体外释放行为

采用S/O/W和W/O/W法,和不同的苄丝肼载药量制作缓释微球,用HPLC考察其释放曲线、突释情况和包封率,实验表明S/O/W法制作的苄丝肼微球缓释效果更好,达到了6d,包封率能达到70%以上,突释情况可以接受,苄丝肼载药量低的微球能达到更高的包封率。     

多巴丝肼联合普拉克索治疗帕金森病的临床疗效

目的:探讨多巴丝肼联合普拉克索治疗帕金森病的临床疗效。方法:以入院病历号为编号,根据随机数字表,将106名帕金森病患者随机分成分两组,每组53例。治疗过程中,给予多巴丝肼片治疗的患者记为对照组(53例);给予多巴丝肼联合普拉克索治疗的患者记为观察组(53例)。连续治疗12周,观察两组患者总疗效、UPDRS评分、HAMD评分及不良反应,探讨其临床治疗价值。结果:1观察组总有效率明显高于对照组总有效率,差异有统计学意义(P0.05)。2与治疗前相比,治疗后两组UPDRS各项评分均明显改善(P0.05),且观察组UPDRS各项评分明显优于对照组(P0.05)。3与治疗前相比,治疗后两组HAMD评分均明显改善(P0.05),且观察组HAMD评分明显优于对照组(P0.05)。结论:多巴丝肼联合普拉克索治疗帕金森病疗效确切,安全可靠,值得临床推广应用。