scholarly journals Deprenyl in Parkinson’s Disease: Mechanisms, Neuroprotective Effect, Indications and Adverse Effects

1992 ◽  
Vol 19 (S1) ◽  
pp. 142-146 ◽  
Author(s):  
Paul Vezina ◽  
Erich Mohr ◽  
David Grimes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Effects ◽  
Neuroprotective Effect ◽  
Dopamine Neurons ◽  
Advanced Parkinson’S Disease ◽  
Ulcer Disease ◽  
Daily Dose ◽  
Higher Doses ◽  
Symptomatic Benefit

ABSTRACT:Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson’s disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear.

scholarly journals Bromocriptine in the Management of End of Dose Deterioration in Parkinson’s Disease

1984 ◽  
Vol 11 (4) ◽  
pp. 452-456 ◽  
Author(s):  
J.D. Grimes ◽  
D.B. King ◽  
O.S. Kofman ◽  
P. Molina-Negro ◽  
A.F. Wilson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Effects ◽  
Early Treatment ◽  
Disability Score ◽  
Advanced Parkinson’S Disease ◽  
Daily Dose ◽  
Small Doses ◽  
The Mean

ABSTRACTThirty-three patients with advanced Parkinson’s disease complicated by end of dose deterioration were treated with bromocriptine. The drug was slowly increased so that by treatment week 24 the mean daily dose of bromocriptine was 22mg and levodopa had been decreased by an average of 15 percent. The majority of improvement in daily fluctuations and Parkinsonian disability score was documented by 8 weeks, at which time the mean daily bromocriptine dose was only 12mg.End of dose deterioration was reduced in 78 percent of the patients (mean 43% improvement). Total Parkinsonian disability score was decreased by 33 percent. Adverse effects were minimal; the most common was mild transient early treatment nausea which occurred in 15 percent of the patients.The slow introduction of small doses of bromocriptine, combined with minimal levodopa reduction, can give Parkinsonian patients significant improvement in end of dose deterioration.

scholarly journals Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

2015 ◽  
Vol 26 (24) ◽  
pp. 4478-4491 ◽  
Author(s):  
BK. Binukumar ◽  
Varsha Shukla ◽  
Niranjana D. Amin ◽  
Philip Grant ◽  
M. Bhaskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Selective Inhibition ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 ­hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

scholarly journals Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

2021 ◽  
Author(s):  
Xiao Yan Sheng ◽  
Shui Yuan Yang ◽  
Xiao Min Wen ◽  
Xin Zhang ◽  
Yong Feng Ye ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Motor Behavior ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Dopamine Neurons ◽  
Therapeutic Modality ◽  
Neuroprotective Effects

Abstract Background: Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo.Methods: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively.Results: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway.Conclusion: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

scholarly journals Use of clozapine in Brazilian patients with Parkinson's disease

2008 ◽  
Vol 66 (3b) ◽  
pp. 611-614 ◽  
Author(s):  
Laura Gomide ◽  
Arthur Kummer ◽  
Francisco Cardoso ◽  
Antonio Lucio Teixeira
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Effects ◽  
Chart Review ◽  
Maximum Dose ◽  
Retrospective Chart Review ◽  
Advanced Parkinson’S Disease ◽  
Brazilian Sample ◽  
Average Maximum ◽  
Psychiatric Complications

Clozapine has been used as an attempt to manage levodopa complications in advanced Parkinson's disease (PD). To investigate the use of clozapine in this context in a Brazilian sample, a retrospective chart review was carried out at the Movement Disorders Clinic from the Federal University of Minas Gerais. This study enrolled 43 PD patients who used or were in use of clozapine. Patients had a mean age of 64 years and a mean UPDRS score of 55. Clozapine was indicated for dyskinesias in 17 patients, for psychosis in 15 and for both reasons in 11. The average maximum dose was 70 mg/day. Twenty six patients used it for a mean of 3.5 years. Twenty nine presented an improvement of their condition, 9 remained clinically stable. Twenty subjects interrupted the use of clozapine, being 9 due to adverse effects. Clozapine may play a role in the management of motor and psychiatric complications in PD, but it is associated with low tolerability.

scholarly journals Ifenprodil Intracerebrally Offers Neuroprotection against 6-OHDA-Induced Toxicity in SD-Rats via Enhancing Autophagy Function

2021 ◽  
Author(s):  
Xinyu Zhao ◽  
Fugang Tian ◽  
Chunmin Guo ◽  
Xin Yu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Beclin 1 ◽  
Dopamine Neurons ◽  
Intracerebral Injection ◽  
Glutamatergic Neurons ◽  
Neuron Damage ◽  
Pathogenic Change ◽  
Related Proteins

The progressive decline of dopamine neurons in the substantia nigra is the main pathogenic change in Parkinson's disease (PD). Studies have found that excessive excitement of glutamatergic neurons causes intracellular calcium overload and induces autophagy impairment, which is one of the main mechanisms of dopamine neuron damage. The neuroprotective effect of Ifenprodil against 6-OHDA-injured mice was studied in this study. Ifenprodil was administered intraperitoneally (i.p.) or intracerebrally to rats who had a nigral-striatum pathway lesioned by 6-OHDA stereotactic brain injection. The ability to move was evaluated. The survival of dopamine neurons in the nigral was determined using HE staining, while TH-positive expression was measured using immunohistochemistry. Western Blot was used to examine the expression of CaM protein and light chain 3 (LC3), Beclin-1, BNIP3LNix, and p62. The results revealed that Ifenprodil improves motor function in 6-OHDA rats, and intracerebral injection is more effective than systemic administration. The same results also found in HE and IHC. Ifenprodil enhanced LC3II, BNIP3LNix, and Beclin-1 while decreasing p62, p-CaMKII, and β-Ca expression. In addition, Ifenprodil reduced the activation of microglia caused by 6-OHDA. Overall, the findings imply that Ifenprodil intracerebrally may protect against Parkinson's disease via modulating autophagy-related proteins during 6-OHDA-induced toxicity.

scholarly journals Da-Bu-Yin-Wan and Qian-Zheng-San to Neuroprotect the Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Gang Gong ◽  
Hong-Mei Sun ◽  
Yi Zhang ◽  
Shu-Jing Zhang ◽  
Yu-Shan Gao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neuroprotective Effect ◽  
Firefly Luciferase ◽  
Dopamine Neurons ◽  
Behavioral Impairment ◽  
Neuroprotective Effects ◽  
Atp Level ◽  
Protein Levels

Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson’s disease (PD). Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA) neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate (ATP) level in the midbrain tissue was detected by firefly luciferase method. MitoKATPchannel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATPchannel subunit expressions.

scholarly journals Method of Addition of Bromocriptine to the Drug Regime of Patients with Advanced Parkinson’s Disease

1981 ◽  
Vol 8 (1) ◽  
pp. 31-34 ◽  
Author(s):  
J. David Grimes ◽  
Mohamed N. Hassan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Effects ◽  
Gradual Increase ◽  
Advanced Parkinson’S Disease ◽  
Number Of Patients ◽  
Concomitant Reduction

SUMMARYUsing a method of a gradual increase of bromocriptine with a concomitant reduction of Sinemet® (levodopa 250 mg + carhidopa 25 mg), 19 patients with advanced Parkinson’s disease have been treated for periods of up to 22 months and 16 of them have shown improvements of varying degrees. Eighteen patients were able to tolerate bromocriptine addition, with early transient adverse effects occurring in seven cases. In contrast to several previously reported studies, it was found necessary to withdraw bromocriptine in only one case.With the drugs currently available, bromocriptine has a role in the management of patients with advanced Parkinson’s disease. The method described here may allow a greater number of patients to be given a trial with this drug.

scholarly journals Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaoyan Sheng ◽  
Shuiyuan Yang ◽  
Xiaomin Wen ◽  
Xin Zhang ◽  
Yongfeng Ye ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Motor Behavior ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Dopamine Neurons ◽  
Therapeutic Modality ◽  
Neuroprotective Effects

Abstract Background Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo. Methods In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively. Results Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway. Conclusions SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

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