• Biomolecules & Therapeutics
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• 제31권4호
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• pp.402-410
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• 2023

Long-term administration of levodopa (L-DOPA) to patients with Parkinson's disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

• 약학회지
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• 제59권3호
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• pp.127-134
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• 2015

The aim of this study was to investigate the correlation among age, symptoms and initial medication (IM), and the tolerance duration of IM in Korean people with Parkinson's disease (PD). We studied 60 patients with untreated early PD who were initially diagnosed in our hospital between Jun 2006 and Sep 2014. We collected data on sex, age at diagnosis, symptom duration until diagnosis, main motor symptoms, frequency and duration of IM through electronic medical records. We divided patients into groups depending on the number of drugs (MONO/COMBI) and whether to contain dopaminergic property (DOPA/NDOPA). We analyzed the correlation between age and symptoms in each two groups and calculated the mean tolerance duration of IM in each of the groups. The mean symptom duration until diagnosis was 12.2 months. The most frequent drug was levodopa formulations (80%) compared to dopamine agonists (58.3%). The number of patients in the COMBI group (63.3%) was more than that in the MONO group (36.7%). Half of the patients in the COMBI group were taking LDF+DA (50%). Except for tremor, no other symptom showed a significant correlation between with IM. The mean tolerance duration of IM was within 200 days. The mean duration for COMBI group (342.7 days) was longer than that for MONO group (209.8 days). Among regimens, the mean tolerance duration of DOPA group (293.3 days) was longer than for NDOPA group (251.4 days). There was no difference in survival curves between any of the two groups. We found that patients experienced symptoms for over a year in Korea. This indicates that diagnosis time is faster than reported in other previous studies. The longest tolerance duration among IM was for dopaminergic combination therapy. More research is needed to design the most appropriate treatment for PD in Korean patients.

• 턱관절균형의학회지
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• 제13권sup호
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• pp.1-8
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• 2023

Objectives: Parkinson's disease (PD) is currently the most rapidly increasing degenerative brain disease due to population aging and westernization of lifestyle. Levodopa is the most commonly used drug to manage PD symptoms. However, levodopa has a problem in that the wearing-off phenomenon occurs as the duration and dose of administration increase. In order to investigate the wearing-off phenomenon in PD patients and devise countermeasures, we conducted a questionnaire survey in Korea. Methods: For the study, a questionnaire with a total of seven items was prepared. Part IV of the MDS-UPDRS (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) and the WOQ-9 (9-symptom Wearing-off Questionnaire) were used as references. Results: Of the 48 patients who completed the questionnaire, all 47 patients who completed the questionnaire experienced the wearing-off phenomenon. Only one of the patients diagnosed with PD a year ago did not experience the wearing-off phenomenon. Patients frequently mentioned a lack of sleep and stress as aggravating factors for wearing-off. They also stated that in order to resolve the off-state, they walked, massaged, warmed up the body, stretched and exercised. Conclusions: Because wearing-off is such a common occurrence, it is thought necessary to develop wearing-off prevention and resolution measures that PD patients can use in their daily lives.

• 한국자기공명학회논문지
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• 제4권1호
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• pp.19-28
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• 2000

Authors evaluated alterations of observable metabolite ratios between the cerebral lesion and the contralateral region related to the clinical symptomatic side in levodopa-treated Parkinson's disease (PD) and investigated correlation between age in patients with PD and metabolite ratios of the lesion. Patients with levodopa-treated PD (n = 54) and age-matched normal controls (n = 15) underwent magnetic resonance spectroscopy (MRS) examinations using a stimulated echo acquisition mode (STEAM) pulse sequence that provided 2$\times$2$\times$2 cm3 volume of interest in the selected regions of substantia nigra (SN) and putamed-globus pallidus (PG). To evaluate dependence of metabolite ratios on age, we divided into two groups (i.e., younger and older age). We quantitatively measured N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), inositols (Ins), and the sum of glutamate (Glx) and GABA levels and obtained proton metabolite ratios relative to Cr using a Marquart algorithm. Compared with the contralateral region, a significant neuronal laterality of the NAA/Cr ratio in the lesion of SN related to the clinical symptomatic side was established (P = 0.01), but was not established in the lesion of PG (P = 0.24). Also, Cho/Cr ratio tended toward significance in the lesion of SN (P = 0.07) and was statistically significant in the lesion of PG(P = 0.01). Compared with that in the younger age group, NAA/Cr ratio in the older age was decreased in the lesion of SN (P = 0.02), while NAA/Cr ratio was not statistically significant in the lesion of PG ( P = 0.21). Significant metabolic alterations of NAA/Cr and Cho/Cr ratios might be closely related with functional changes of neuropathological process in SN and PG of levodopa treated PD and could be a valuable finding for evaluation of the PD. A trend of NAA/Cr reduction, being statistically significant in older patients, could be indicative of more pronounced neuronal damage in the SN of the progressive PD.

• Journal of Korean Neurosurgical Society
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• 제30권8호
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• pp.976-980
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• 2001

Objectives : For Parkinsonian patients who had not reacted favorably on drug therapy are good candidate for ventroposterolateral pallidotomy, although not curative. We studied these patients after unilateral pallidotomy, to confirm the effectiveness and safety of this procedure. Methods : We evaluated the 17 patients with idiopathic Parkinson's diesease who had undergone unilateral posteroventral pallidotomy. All patients responded to levodopa initially. Mean age was 55 years(38-75years), and mean duration of disease was 9.8 years(3-20years). Pre-and postoperative evaluation at 3 month intervals included Unified Parkinson's Disease Rating scale(UPDRS) scoring, Hoehn and Yahr(H & Y) staging, and neuropsychological examinations. Results : Pallidotomy significantly improved parkinsonian symptom(tremor, rigidity, bradykinesia, dyskinesia, sensory symptom). Nine of 10 patients who showed dyskinesia preoperatively significant improvement. The mean dose of levodopa in 9 patients was lowered. The mean H & Y score and UPDRS score were improved in on and/or off time in 15 patients. Among patients who were not improved, one patient worsened, and the others showed no change. The mean overall UPDRS off score changed from 76 preoperatively to 44(33%) at 6 months and from 70 to 52(25%) at 1 year. Transient surgical morbidity was showen in four patients and included dysarthria, hypotonia and confusion. Conclusion : We conclude that pallidotomy is safe and effective in patients who have levodopa-reponsive parkinsonism with severe symptom fluctuation. Unilateral pallidotomy also considered helpful to ipsilateral symptom. Unilateral pallidotomy can improve all of parkinsonian's symptom and allow to reduce the levodopa medication. Most of patients show satisfactory results.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 NEW STRATEGY FOR DRUG DEVELOPMENT IN POST-GENOMIC ERA(대한약학회)
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• pp.279.1-279.1
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• 2000

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.220-222
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• 2002

The concentration effect relationship (pharmacokinetic pharmacodynamic model, PKPD) of drugs used for Parkinson's disease is complex. The benefits and adverse effects of drug treatment have to be considered in terms of short term and long term effects. Acute effects, observed over hours and days, reflect symptomatic benefit while chronic effects, observed over months and years, also reveal influences on the progress of the disease. (omitted)

• 대한한방내과학회지
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• 제45권2호
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• pp.219-233
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• 2024

A 69-year-old female diagnosed with idiopathic Parkinson's disease and treated with anti-Parkinsonian medications, including levodopa, for 7 years presented with complaints of wearing-off phenomenon and delayed onset of medication efficacy, resulting in postural instability and feeling of severe exhaustion. The patient underwent a 50-day course of treatment with Bonoesikpungjigyeong-tang formula. The effects of the treatment were evaluated by recording the average time to onset of medication efficacy, the average time to medication wearing-off, and discomfort due to wearing-off phenomenon. Postural instability was assessed using the Numeric Rating Scale (NRS). The patient's overall quality of life was assessed using the EQ-5D-3L. After 50 days of treatment, the average time to onset of medication efficacy decreased, and the average time to medication wearing-off increased. Discomfort due to wearing-off phenomenon and postural instability decreased. This case suggests that Bonoesikpungjigyeong-tang might be an alternative for improving discomfort caused by long-term levodopa intake.

• 한국임상약학회지
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• 제30권2호
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• pp.81-86
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• 2020

Background: The number of patients with dementia continues to increase as the age of aging continues to grow. Psychiatric symptoms caused by senile dementia are controlled using antipsychotics. However, these antipsychotics can lead to Parkinson's disease, and abuse of dopamine derivatives such as levodopa among Parkinsonian drugs can lead to psychosis. Therefore, we evaluated the patterns of prescribed antipsychotics and antiparkinsonian drugs in patients with senile dementia. Methods: We used data from the sample of elderly patients from the Health Insurance Review and Assessment Service (HIRA-APS-2016). We analyzed the patterns of prescribing antipsychotics and antiparkinsonian drugs including prescribed daily dosage, period of prescription, and number of patients with both antipsychotics and antiparkinsonian drugs for senile dementia. Results: Among the 159,391 patients with dementia included in this analysis, 4,963 patients (3.1%) and 16,499 patients (10.4%) were prescribed typical and atypical antipsychotic drugs, respectively. The most frequently prescribed typical antipsychotic was haloperidol (4,351 patients with dementia), whereas the atypical agent was quetiapine (12,719 patients). The most frequently prescribed antiparkinsonian drugs were in the order of levodopa/carbidopa, benztropine, and ropinirole. In addition, 1,103 and 3,508 patients prescribed typical and atypical antipsychotics, respectively, were co-prescribed antiparkinsonian drugs. Conclusions: Atypical antipsychotics were the preferred prescription in patients with senile dementia. The prescription dose was relatively low; however, the average treatment duration was mostly long-term. Selection of antipsychotics and/or antiparkinsonian drugs should be made carefully in senile dementia and the causal relationship of adverse drug reactions needs further study.

• 성인간호학회지
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• 제22권1호
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• pp.60-69
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• 2010

Purpose: The aim of this study was to investigate the level of resilience and related factors in patients with Parkinson's disease (PD) in Korea. Methods: Data were obtained from 148 patients using the Resilience Scale (RS), Beck's Depression Inventory (BDI), and Spielberger's Anxiety Inventory (AI). Results: The mean scores of the RS, BDI, and AI were $127.7{\pm}21.6$, $12.9{\pm}9.3$, and $41.9{\pm}11.1$, respectively. The RS score was strongly correlated with the BDI score (r=-.531, p<.001) and the AI (r=-.572, p<.001). The resilience was significantly revealed by household income (F=4.002, p=.009) and presence of a hobby (t=-3.300, p=.001). In addition, resilience was significantly correlated with age of disease onset (r=.164, p=.046), years of living with PD (r=-.262, p=.001), and the length of treatment with levodopa (r=-.283, p<.001). From the stepwise multiple regression analysis, the most important factors related to the RS score were the AI score, household income, and length of treatment with levodopa. Conclusion: Understanding these factors is essential for developing effective interventions to improve resilience in patients with PD.