Levodopa

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Evaluation of the Cytotoxicity of Levodopa and its Complex with Hydroxypropyl-ss-Cyclodextrin (HP-ss-CD) to an Astrocyte Cell Line.[Pubmed:25941458]

Malays J Med Sci. 2014 Dec;21(Spec Issue):6-11.

A simple, reliable a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tet razolium, (MTS) assay was conducted to evaluate the potential cytotoxic effects of Levodopa, a "gold standard therapy" for Parkinsonism, and its complex with Hydroxypropyl-beta-Cyclodextrin (HP-beta-CD) on an astrocyte cell line. The cells were incubated in a range of concentrations from 4.69 to 300 mug/mL Levodopa, HP-beta-CD or the complex for up to 72 hours. At every 24-hour interval, the optical density (OD), which reflects the number of viable cells, was recorded. In general, linear dose-dependent cytotoxicity profiles were observed for the cells subjected to Levodopa or the complex, whereas a slightly triphasic response was observed for the cells exposed to HP-beta-CD. A significant difference (P < 0.05) in cytotoxicity was detected between the HP-beta-CD-treated group and the Levodopa-treated group. In particular, we observed that the cells treated with the complex, even at the highest concentrations (> 200 mug/mL), exhibited improved tolerability in a time-dependent manner, which may indicate the potential ability of HP-beta-CD to mask the toxic effects of Levodopa via complexation.

Levodopa enhances explicit new-word learning in healthy adults: a preliminary study.[Pubmed:25900350]

Hum Psychopharmacol. 2015 Sep;30(5):341-9.

OBJECTIVE: While the role of dopamine in modulating executive function, working memory and associative learning has been established; its role in word learning and language processing more generally is not clear. This preliminary study investigated the impact of increased synaptic dopamine levels on new-word learning ability in healthy young adults using an explicit learning paradigm. METHOD: A double-blind, placebo-controlled, between-groups design was used. Participants completed five learning sessions over 1 week with Levodopa or placebo administered at each session (five doses, 100 mg). Each session involved a study phase followed by a test phase. Test phases involved recall and recognition tests of the new (non-word) names previously paired with unfamiliar objects (half with semantic descriptions) during the study phase. RESULTS: The Levodopa group showed superior recall accuracy for new words over five learning sessions compared with the placebo group and better recognition accuracy at a 1-month follow-up for words learnt with a semantic description. CONCLUSIONS: These findings suggest that dopamine boosts initial lexical acquisition and enhances longer-term consolidation of words learnt with semantic information, consistent with dopaminergic enhancement of semantic salience.

Coadministration of hydroxysafflor yellow A with levodopa attenuates the dyskinesia.[Pubmed:25914172]

Physiol Behav. 2015 Aug 1;147:193-7.

Levodopa (L-DOPA) is used as the most effective drug available for the symptomatic treatment of Parkinson's disease (PD). However, long-term treatment of L-DOPA frequently causes complications, including abnormal involuntary movements such as dyskinesia and response fluctuations in PD patients. In the present work, we investigated whether hydroxysafflor yellow A (HSYA) ameliorates L-DOPA-induced dyskinesia and motor fluctuations in the 6-hydroxydopamine-lesioned rat model of PD. Valid PD rats were treated daily with vehicle, HSYA alone, L-DOPA, or a combination of HSYA plus L-DOPA for 21days, respectively. L-DOPA (8mg/kg) and benserazide (15mg/kg) were treated intraperitoneally. HSYA was administrated intraperitoneally at a dose of 10mg/kg. The abnormal involuntary movements and rotational behavior were evaluated. The expression of the dopamine D3 receptor in the striatum was also assayed. The results demonstrated that daily administration of L-DOPA to PD rats for 21days induced a steady expression of dyskinesia. Coadministration of HSYA with L-DOPA significantly ameliorated L-DOPA-induced dyskinesia. The combination treatment also prevented the shortening of the motor response duration that defines wearing off motor fluctuations. HSYA also inhibited the increase of expression of the dopamine D3 receptor in the striatum. These findings demonstrated that HSYA provided anti-dyskinetic relief against L-DOPA in a preclinical model of PD via regulating the expression of the dopamine D3 receptor. The combination of L-DOPA and HSYA also reduced the likelihood of wearing off development, and may thus support the utility of such compounds for the improved treatment of PD.

[Effects of a single dose levodopa on heart rate variability in Parkinson's disease].[Pubmed:25916922]

Zhonghua Yi Xue Za Zhi. 2015 Feb 17;95(7):493-5.

OBJECTIVE: To explore the effects of Levodopa on heart rate variability (HRV) in Parkinson's disease (PD). METHODS: A total of 48 PD patients (M:F = 35: 13, mean age: 59 +/- 6 years, duration of illness: 4.7 +/- 1.8 years, Hoehn & Yahr stage: 2.2 +/- 0.3) on a stable dose of Levodopa were recruited from January 2012 to May 2014.For confirming autonomic dysfunction, the baseline patient data (12 hours off-medication) were compared with a control group consisting of 48 age and gender-matched healthy subjects (M: F = 35: 13, mean age 58 +/- 6 years). Resting lead II electrocardiogram (ECG) was recorded at baseline and continuously after two tablets of 100/10 mg Levodopa/carbidopa.However, 5-min segments were selected from every quarter, i.e., Q1 (0-15 min), Q2 (15-30 min), Q3 (30-45 min) and Q4 (45-60 min). Artifact-free 5-min segments of ECG were analyzed offline to acquire the parameters of heart rate variability in time and frequency domains. RESULTS: At baseline, PD patients had a significantly reduced standard deviation of normal-to-normal intervals (SDRR) [(24 +/- 4) vs (26 +/- 4) ms, P < 0.01)] and total power (TP) [(569 +/- 180) vs (652 +/- 205) ms(2), P < 0.05] when compared to controls. Comparing of HRV in PD patients at baseline and during first hour after drug administration, we observed significant increase in SDRR [(29 +/- 12) vs (24 +/- 8) ms, P < 0.05)], TP [(708 +/- 253) vs (569 +/- 180) ms(2), P < 0.01], low frequency power (LF) [(203 +/- 98) vs (168 +/- 60) ms(2), P < 0.05) ] and high frequency power (HF) [158 +/- 86) vs (114 +/- 90) ms(2), P < 0.05] in Q3. CONCLUSION: The results suggest an improvement in the overall variability of heart rate resulting from an enhanced vagal tone.

L-DOPA (Levodopa) is an orally active metabolic precursor of neurotransmitters dopamine. L-DOPA can cross the blood-brain barrier and is converted into dopamine in the brain. L-DOPA has anti-allodynic effects and the potential for Parkinson's disease.

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