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1.
Abstract. The absorption and gastric metabolism of L-dopa (L-dihydroxyphenylalanine) were studied in 14 Parkinsonian patients. Patients were given p. o. 25 μCi (500 mg) 14C L-dopa labelled at the β-carbon mixed with 2 g polyethylene glycol as a dilution marker. Absorption was evaluated by determining the gastric rate of absorption, gastric clearance, serum levels, and urinary excretion of 14C. L-dopa and its metabolites in the gastric juice and serum were fractionated by column chromatography. Patients with gastric juice pH of 1.2-2.1 had a gastric rate of absorption of 62.6±4.7 mg/h with a gastric clearance of 31.7.4.1 ml/h. The gastric emptying time was 228±96min. 17.2–26.4% of total radioactivity in the gastric juice were dopa metabolites. Patients with gastric pH of 6.9-7.2 had a very rapid emptying time (an average of 22 min.) with no gastric absorption. The amount of metabolites in their gastric juice was insignificant. Gastric absorption and emptying time were reduced in patients when the gastric pH was raised to 3.5-4.5 with antacids. Serum peak concentrations were higher and more rapidly achieved in patients with high gastric pH than in those with low pH.
The most rapidly achieved and highest serum peak levels were observed in patients with partial gastrectomy and in those who were given the drug by duodenal infusion. It appears that direct absorption of L-dopa by the stomach may be limited by gastric metabolism of the drug, a possibility supported by the study in vitro of human stomach tissue obtained at surgery. The inverse relationship between the gastric emptying time and serum levels suggests that the intestine is the major site of L-dopa absorption. Thus factors that prolong gastric emptying time may lower serum levels of L-dopa by delaying access of the drug to the site of absorption and by increasing metabolism before absorption.  相似文献
2.
Levodopa is the medication of choice for Parkinson's disease. The biological complexity of levodopa and of its main derivatives makes their determination important in the clinical field. The aim of this study was to develop an HPLC method for the simultaneous determination of serum concentrations of levodopa, dopamine, 3-O-methyldopa and alpha-methyldopa. We compared UV and fluorimetric detection of native and derivatised compounds. Though less sensitive than other methods, UV detection is important to exclude naturally fluorescent, interfering substances. Fluorimetric detection of derivatised compounds is more sensitive than UV detection. Since 3-O-methyldopa does not react with the derivatising agent 1,2-diphenylethylenediamine, it cannot be detected. For simultaneous determination of the four compounds after pharmacological treatment of patients we therefore advise fluorimetric detection of the native compound.  相似文献
3.
The time course of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in four rat brain areas (hypothalamus, hippocampus, striatum and olfactory bulbs) were investigated after treatment with L-dopa (125 mg/kg, ip) + benserazide (50 mg/kg, ip). 5-HTP levels increased as early as 0.5 h, showed maximum accumulation at 1.5 h and returned to control levels within 4 h, while 5-HT was markedly decreased in all four structures, with a maximum effect at 1.5 h (approximately -70%) in the four areas. The decrease in 5-HT was not accompanied by changes in 5-HIAA levels. In agreement with previous studies, these data demonstrate that L-dopa loading interferes with serotonin metabolism in the rat brain. However, in addition to the releasing action of newly-synthesized dopamine, the accumulation of 5-HTP and the parallel decrease in 5-HT indicate a reduction in 5-HT synthesis. This inhibition could be explained by a competitive effect of L-dopa for aromatic aminoacid decarboxylase activity.  相似文献
4.
目的 研究左旋多巴对黑质细胞的神经毒性作用。探讨合理应用左旋多巴治疗帕金森病的方法。方法 通过6-羟基多巴胺脑立体定向注射术制作大鼠帕金森病模型。采用TUNEL方法观察左旋多巴小(每天每公斤10mg),中(每天每公斤50mg),大(每天每公斤100mg)三种不同剂量,不同的作用时间(1d,3d,5d,7d)对帕金森病大鼠黑质细胞的毒性作用,并观察治疗后7d各项指标的变化。结果 帕金森病大鼠细胞凋亡数随着左旋多巴治疗的时间,剂量增加而增加。结论 左旋多巴能加速帕金森病大鼠黑质细胞凋亡,小剂量,间隔使用左旋多巴能有效减少其神经毒性作用。  相似文献
5.
本文对61例手足徐动型脑瘫儿童应用美多巴的临床效果、不良反应、用药剂量、加量间隔、用量与效果的关系进行了研究。结果显示:以脑瘫儿童日常生活能力评价表作为疗效评价标准,用美多巴治疗组与不用美多巴治疗组在第3次评价时有极显著性的差异(P<0.001)。因此说明用美多巴治疗是有效的,而其不良反应轻且短暂。平均开始用量为9mg/kg/d,最大开始用量可达26mg/kg/d,平均间隔一周后加量,最短间隔一天,可加量至20mg/kg/d,最大可加量至38mg/kg/d,用量与效果不存在相关性。本文对今后的研究也提出了建议。  相似文献
6.
Summary— This study aims to evaluate whether or not the kinetics of L-dopa, its main metabolites (3-O-methyldopa, 3-OMD, homovanilic acid, HVA and 3,4-dihydroxyphenylacetic acid, DOPAC) and carbidopa, vary according to the 24-hour scale in rats. Four groups of seven adult male Wistar AF EOPS rats were used for these experiments; each group received L-dopa (200 mg·kg−1 ip) and carbidopa (20 mg·kg−1 ip) at 1000, 1600, 2200 or 0400 hours. L-dopa, 3-OMD, DOPAC, HVA and carbidopa were simultaneously determined by specific ion-pair reversed-phase high performance liquid chromatography with electrochemical detection. A temporal variation of the kinetics of both L-dopa and carbidopa was demonstrated with higher plasma clearance and lower area under concentration curve after the administration at 2200 hours. Moreover, a temporal variation of the metabolism of L-dopa was indirectly documented by temporal variation in kinetics of 3-OMD, DOPAC and HVA.  相似文献
7.
Summary— l -Dopa is converted to dopamine by aromatic- l -amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of l -Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single l -Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg l -Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. l -Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 μg/24 h) accounted for 0.8% of the daily oral l -Dopa dose and represented 10% of total urinary dopamine excretion. l -Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion.  相似文献
8.
Abstract . The permeability of L-dopa across the blood-brain barrier was studied in twelve patients by means of the indicator dilution method. The extraction of [l-14C]L-dopa and [3-14C]L-dopa was 11.7% and 10.4%, respectively. After pretreatment with carbi-dopa the extraction was unchanged (13.5% and 11.6%). The permeability coefficient ( P ) was calculated to 0.9×10-5 cm s-1.  相似文献
9.
A large body of evidence using experimental animal models shows that the nicotinic cholinergic system is involved in the control of movement under physiological conditions. This work raised the question whether dysregulation of this system may contribute to motor dysfunction and whether drugs targeting nicotinic acetylcholine receptors (nAChRs) may be of therapeutic benefit in movement disorders. Accumulating preclinical studies now show that drugs acting at nAChRs improve drug-induced dyskinesias. The general nAChR agonist nicotine, as well as several nAChR agonists (varenicline, ABT-089 and ABT-894), reduces l-dopa-induced abnormal involuntary movements or dyskinesias up to 60% in parkinsonian nonhuman primates and rodents. These dyskinesias are potentially debilitating abnormal involuntary movements that arise as a complication of l-dopa therapy for Parkinson's disease. In addition, nicotine and varenicline decrease antipsychotic-induced abnormal involuntary movements in rodent models of tardive dyskinesia. Antipsychotic-induced dyskinesias frequently arise as a side effect of chronic drug treatment for schizophrenia, psychosis and other psychiatric disorders. Preclinical and clinical studies also show that the nAChR agonist varenicline improves balance and coordination in various ataxias. Lastly, nicotine has been reported to attenuate the dyskinetic symptoms of Tourette's disorder. Several nAChR subtypes appear to be involved in these beneficial effects of nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with nicotine's neuroprotective effects, suggest that nAChR drugs have potential for future drug development for movement disorders.  相似文献
10.
Pain is a frequently observed non-motor symptom of patients with Parkinson’s disease. In some patients, Parkinson’s-related pain responds to dopaminergic treatment. In the present study, we aimed to elucidate whether subthalamic deep brain stimulation has a similar beneficial effect on pain in Parkinson’s disease, and whether this effect can be predicted by a pre-operative l-dopa challenge test assessing pain severity. We prospectively analyzed 14 consecutive Parkinson’s patients with severe pain who underwent subthalamic deep brain stimulation. In 8 of these patients, pain severity decreased markedly with high doses of l-dopa, irrespective of the type and localization of the pain symptoms. In these patients, subthalamic deep brain stimulation provided an even higher reduction of pain severity than did dopaminergic treatment, and the majority of this group was pain-free after surgery. This effect lasted for up to 41 months. In the remaining 6 patients, pain was not improved by dopaminergic treatment nor by deep brain stimulation. Thus, we conclude that pain relief following subthalamic deep brain stimulation is superior to that following dopaminergic treatment, and that the response of pain symptoms to deep brain stimulation can be predicted by l-dopa challenge tests assessing pain severity. This diagnostic procedure could contribute to the decision on whether or not a Parkinson’s patient with severe pain should undergo deep brain stimulation for potential pain relief.  相似文献
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