Correlation between brain dopamine levels and 1-dopa activity in anti-Parkinson tests

The activity of l-dopa and dopamine in anti-oxotremorine and reserpine reversal tests in mice was compared with l-Dopa-induced changes in brain dopamine levels. Oxotremorine-induced tremors and hypothermia were prevented by both l-Dopa and dopamine despite the fact that only l-Dopa increased brain dopamine levels. Furthermore, a peripheral decarboxylase inhibitor that increased brain dopamine levels completely abolished the activity of l-Dopa in the oxotremorine test. Reserpine-induced ptosis was also reversed by l-Dopa and dopamine. However, reserpine-induced catatonia was reversed only by l-Dopa and was directly correlated with brain dopamine levels. Pretreatment with a peripheral decarboxylase inhibitor increased l-Dopa reversal of reserpine catatonia correlating with increased brain dopamine levels. Since oxotremorine-induced tremors and hypothermia as well as reserpine-induced ptosis can be influenced by peripheral drug effects, the reversal of reserpine induced catatonia appears to be the better model to use in a search for anti-Parkinson drugs.     

“抗帕颗粒”对帕金森病模型鼠行为学的影响

目的探讨"抗帕颗粒"对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)帕金森病(PD)模型小鼠行为学的影响。方法 90只健康雄性C57BL/6小鼠,鼠龄8~12w,随机分为3组:正常对照组30只、PD模型对照组30只、PD模型干预组30只;MPTP腹腔注射(40mg·kg-1·d-1×7)制备小鼠PD模型;正常对照组及PD模型对照组予生理盐水1m L·d-1灌胃,PD模型干预组给予"抗帕颗粒"(浓度800mg·m L-1)按40mg·kg-1·d-1灌胃,连续喂养4个月。比较分析各组、各时间点(15d、1个月、2个月、3个月、4个月)爬杆实验、悬挂实验、游泳实验等行为学评分情况。结果 1各组实验动物存活情况,正常对照组30只最终均存活,PD模型对照组4个月时存活27只,PD模型干预组4个月时存活28只;2各组爬杆实验分值情况:正常对照组与PD模型对照组比较,各时间点评分均P0.01。正常对照组与PD模型干预组比较,15d、1个月时均P0.01,2、4个月时P0.05,3个月时P0.05。PD模型对照组与PD模型干预组比较,15d、1个月时,均P0.05,2、4个月时,P0.05,3个月时,P0.01。PD模型干预组各时间点分值比较,15d评分较1个月时,P0.05,较2月时,P0.05,较3、4个月时均,P0.01;1个月评分较2个月时,P0.05,较3、4个月时均,P0.01;2个月评分较3、4个月时均,P0.05;3个月评分较4个月时,P0.05;3各组悬挂实验分值情况,正常对照组与PD模型对照组比较,各时间点评分均P0.01。正常对照组与PD模型干预组比较,15d、1个月时均P0.01,2、3、4个月时均P0.05。PD模型对照组与PD模型干预组比较,15d、1个月时均P0.05,2个月时P0.05,3、4个月时均P0.01。PD模型干预组各时间点分值比较,15d评分较1个月时P0.05,较2、3、4个月时均P0.05;1个月评分较2、3、4个月时均P0.05;2个月评分较3、4个月时均P0.05;3个月评分较4个月时P0.05;4各组游泳实验分值情况:正常对照组与PD模型对照组比较,各时间点评分P均0.01。正常对照组与PD模型干预组比较,15d、1个月时均P0.01,2、3、4个月时均P0.05。PD模型对照组与PD模型干预组比较,15d、1个月、2个月时均P0.05,3、4个月时P均0.01。PD模型干预组各时间点分值比较,15d评分较1个月、2个月时均P0.05,较3、4个月时均P0.05;1个月评分较2个月时P0.05,较3、4个月时均P0.05;2个月评分较3、4个月时均P0.05;3个月评分较4个月时P0.05。结论 "抗帕颗粒"对MPTP诱发的C57BL/6小鼠PD模型行为学具有良好的改善作用;但起效较慢,至2-3个月左右开始显现疗效;在应用过程中应注意足量、足程等问题,以保证其作用的有效性、持久性。另外,"抗帕颗粒"对游泳动作的改善相对较慢,需要更持久、更足量的治疗,显示中药制剂作用的缓慢性和局限性,提示联合使用多巴制剂中西医结合治疗PD的必要性。     

抗帕颗粒联合美多巴治疗血管性帕金森综合征

目的　探讨抗帕颗粒联合美多巴治疗血管性帕金森综合征的疗效。　 方法 　 32例血管性帕金森患者同时应用抗帕颗粒及美多巴 ,于治疗前、治疗后半月、1月、3月给予UPDRS评分。　 结果 　加用抗帕颗粒后美多巴用量减少 1/2以上 ,副作用发生率下降 ,症状减轻 ,治疗后 3月UPDRS评分和治疗前相比明显下降 (P <0 0 1)。　 结论 　抗帕颗粒联合美多巴治疗血管性帕金森综合征能提高疗效 ,减少副作用 ,降低美多巴用量 ,为中西医结合治疗帕金森病的良方     

Fracture Risk Associated with Parkinsonism and Anti-Parkinson Drugs

We studied fracture risk associated with parkinsonism (including Parkinson’s disease) and drugs used to treat these conditions in a case-control study. Cases were all subjects with any fracture during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. Exposure was a diagnosis of parkinsonism or use of anticholinergic drugs, levodopa alone or in combination with carbidopa, and/or catechol-O-methyl transferase (COMT) inhibitors, dopamine agonists, or monoamine oxidase B (MAO-B) inhibitors and a number of other confounders. Parkinsonism was associated with a crude odds ratio (OR) of any fracture of 2.2 (95% confidence interval [95% CI] 2.0–2.5) and an adjusted OR of 1.2 (95% CI 1.0–1.4), the risk being higher especially in males younger than 75 years. Levodopa was associated with an increased overall fracture risk and an increased risk of hip fractures in high doses. Dopamine agonists, anticholinergic drugs, and MAO-B inhibitors were not associated with increased fracture risk except for hip fractures at high doses for MAO-B inhibitors and hip fractures at median doses for dopamine agonists. Neuroleptics were associated with increased risk of fractures in almost all skeletal sites and doses. In conclusion, parkinsonism was associated with increased risk of fractures, especially among males younger than 75 years, and the risk was significantly attenuated upon adjustment for confounders. Use of neuroleptics and, to some degree, levodopa was associated with increased risk of fractures.     

Drugs for Parkinson's disease reduce tremor induced by physostigmine

Summary The effects of anticholinergic and dopaminergic drugs used for Parkinson's disease were studied on the tremor induced by physostigmine (0.3–3.0 mg/kg) in rats. For the measurement of tremor a new electronic device was employed. Atropine (0.3–1.2 mg/kg) and biperiden (0.01–1.0 mg/kg) reduced the physostigmine-induced tremor in a dose-related manner and could abolish it. Biperiden was less potent than atropine. Methylatropine in a dose of 1.2 mg/kg slightly inhibited the tremor. Amantadine (0.3–3.0 mg/kg) reduced the tremor but only to a certain degree. Bromocriptine (0.1–10.0 mg/kg) reduced it in a manner that was not dose-related. Pimozide potentiated the tremor in the dose of 0.2 mg/kg but not in larger doses.At the onset of the tremor, a small decrease in rectal temperature occurred. The hypothermia lasted significantly longer than the tremor. Neither the anticholinergic nor the dopaminergic anti-Parkinson drugs altered the hypothermic effect of physostigmine.The results show that those anti-Parkinson drugs, which act by increasing the dopaminergic activity can counteract the tremor induced by physostigmine. However, these drugs are clearly less active than the anticholinergic anti-Parkinson drugs.     

抗帕颗粒对帕金森病模型小鼠酪氨酸羟化酶神经元的影响

目的 探讨抗帕颗粒对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)帕金森病(PD)模型小鼠黑质纹状体酪氨酸羟化酶(TH)阳性神经元的影响。方法 90只健康雄性C57BL/6小鼠,鼠龄8～12周,并随机分为3组,即正常对照组30只、PD模型对照组30只、PD模型干预组30只; MPTP腹腔注射(40 mg·kg^-1·d^-1×7 d)制备小鼠PD模型; 正常对照组及PD模型对照组予生理盐水1 mL·d^-1灌胃,PD模型干预组给予抗帕颗粒40 mg·kg^-1·d^-1灌胃,连续喂养4个月; 黑质纹状体切片、HE染色、免疫组织化学染色TH神经元及Western blotting检测TH蛋白的表达量。结果 ①正常对照组30只(30/30只)最终均存活,PD模型对照组4个月存活27只(27/30只),PD模型干预组4个月存活28只(28/30只); ②PD模型对照组、PD模型干预组小鼠每次注射MPTP后先有短暂兴奋[持续(7.61±2.17)min],表现为四处窜跳,随即出现全身中重度震颤,皮毛及尾巴时有竖立,活动减少,持续(24.23±3.89)min后震颤消失,随后出现活动减少; ③HE染色显示正常对照组大量褐色TH阳性细胞,PD模型对照组TH阳性细胞数明显减少,PD模型干预组TH阳性细胞数有所增加; ④免疫组织化学染色后经Imagepro-Plus 5.1系统分析,正常对照组TH阳性细胞面积为64 145 μm²,高倍镜下可见大量胞质为褐色颗粒的TH阳性细胞; PD模型对照组TH阳性细胞染色面积为40 012 μm²,高倍镜下见TH细胞数明显减少; PD模型干预组TH阳性细胞染色面积为60 952 μm²,高倍镜下见TH阳性细胞数较PD模型对照组增加; ⑤Western blotting检测显示正常对照组TH蛋白表达量与PD模型对照组和PD模型干预组比较均有明显差异(P<0.001),PD模型对照组TH蛋白表达量与PD模型干预组比较也有明显差异(P<0.05)。结论 抗帕颗粒可使PD小鼠黑质纹状体中多巴胺能神经元一定程度地减少丢失,对多巴胺能神经元的数量、形态及功能具有一定的保护作用。     

我院2011-2013年抗帕金森病药使用分析

目的:了解我院抗帕金森病(PD)药的使用情况,为临床合理用药提供参考。方法:收集我院2011-2013年每年11-12月诊断为PD的所有门诊处方共计1 526张,从中随机抽取450张,收集患者的性别、年龄、用药情况等信息资料,对不同年龄段患者用药情况进行统计分析。同时以我院2011-2013年抗PD药的使用记录为依据,采用回顾性调查方法,对抗PD药的年销售金额、各品种销售金额排序、用药频度(DDDs)、日均费用(DDC)等进行统计、分析。结果:普拉克索在年轻患者中的使用率较高,销售金额和DDDs增长最快,年销售金额所占比例增长幅度最大;而复方左旋多巴年销售金额所占比例逐年下降。DDDs排名靠前的分别为金刚烷胺、苯海索,且其DDC均较低。随着患者年龄的增长,加用复方左旋多巴的处方比例逐渐增加。结论:我院PD治疗方案较合理,但由于PD患者经济负担较重,在药物选择上需要根据患者病情的特点、年龄、职业、经济状况等因素综合考虑,从中选择合适的药物。     

“抗帕颗粒”对帕金森病模型鼠α-syn异常聚集的影响

目的探讨"抗帕颗粒"对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)帕金森病(PD)模型小鼠黑质纹状体区α-突触共核蛋白(α-syn)异常聚集的影响。方法 90只健康雄性C57BL/6小鼠,鼠龄8~12w。随机分为3组,正常对照组30只、PD模型对照组30只、PD模型干预组30只。MPTP腹腔注射40mg·Kg-1·d-1×7制备小鼠PD模型;正常对照组及PD模型对照组予生理盐水1ml·d-1灌胃;PD模型干预组给予"抗帕颗粒"40mg·kg-1·d-1灌胃,连续喂养4个月。比较分析各组4月时黑质纹状体区α-syn聚集情况。结果 (1)正常对照组30只(30/30只)最终均存活,PD模型对照组4个月时存活27只(27/30只),PD模型干预组4个月时存活28只(28/30只);(2)PD模型对照组、PD模型干预组小鼠每次注射MPTP后,先有短暂兴奋(持续7.61±2.17min),表现为四处窜跳;随即出现全身中重度震颤,皮毛及尾巴时有竖立,活动减少,持续24.23±3.89min后震颤消失;随后出现活动减少;(3)黑质纹状体区α-syn免疫荧光双染检测;(3)PD模型对照组较正常对照组明显增多,PD模型干预组较PD模型对照组有所减少,但仍较正常对照组增多;(4)Western blotting检测α-syn蛋白量的表达,正常对照组与PD模型对照组比较,P0.001;与PD模型干预组比较,P0.001;PD模型对照组与PD模型干预组比较,P0.05。结论 "抗帕颗粒"对PD小鼠黑质纹状体区α-syn异常聚集具有一定程度的抑制作用,阻断氧化应激反应可能是这种保护作用的关键机制,有望改善PD治疗现状并在临床进一步推广应用。     

Hypokinesia produced by anterolateral hypothalamic 6-hydroxydopamine lesions and its reversal by some antiparkinson drugs

Hypokinesia produced by stereotaxic microinjection of solutions of 6-hydroxydopamine into the anterolateral hypothalamus of male rats is accompanied by a generalized reduction in brain noradrenaline levels and a reduction of dopamine in the striatum and cerebral cortex. The hypokinesia is reversed by the putative dopamine-receptor agonists apomorphine, ET-495 and CB-154 as well as by the amino acids L-Dopa and m-tyrosine when administered in combination with the peripheral decarboxylase inhibitor Ro 4-4602. The relative importance of noradrenergic and dopaminergic systems in the mediation of the action of anti-akinesia drugs is discussed.     

"抗帕颗粒"对健康志愿者血液流变学和甲襞微循环的影响

目的探讨“抗帕颗粒”对健康志愿者血液流变学和甲襞微循环的影响。方法32例健康志愿者予以“抗帕颗粒”7.5 g,2次/日冲服,疗程15 d。于用药前后分别测定相关指标。结果用药后血液流变学各项指标显著下降,甲襞微循环加权积分值明显下降,肝肾功能及血象无明显变化。结论 “抗帕颗粒”作为中西医结合治疗帕金森综合征的新药,明显改善健康志愿者的血液流变学和甲襞微循环,且无肝肾损害及抑制血细胞等副作用。