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1.
Sleep Med ; 119: 379-388, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761607

RESUMO

BACKGROUND: Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change sleep parameters, thus having adverse effects on patient condition. This meta-analysis clarified the effects of DAs used in RLS treatment on the sleep architecture. METHODS: PubMed, Embase, and Cochrane Central databases were searched for randomized control trials (RCT) (up to October 2023) that discussed the effects of DAs on sleep architecture in patients with RLS. A meta-analysis employing a random-effects model was conducted. The patients were divided into subgroups according to individual DAs and treatment duration (1 day or ≥4 weeks). RESULTS: Thirteen eligible randomized placebo-controlled trials were included in the assessment. The effects of three DAs (i.e., pramipexole, ropinirole, and rotigotine) on rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were analyzed. Overall, pramipexole significantly improved SE but decreased the percentage of REM sleep among treated patients. Ropinirole also enhanced SE compared with the placebo group. Rotigotine did not affect SE and REM sleep. Subgroup analysis found that pramipexole used for 1 day and ≥4 weeks significantly diminished the percentage of REM sleep. Ropinirole used for 1 day showed similar REM sleep patterns. Finally, none of the three DAs affected SWS. CONCLUSIONS: This meta-analysis demonstrated that DAs significantly affect sleep parameters.


Assuntos
Agonistas de Dopamina , Pramipexol , Síndrome das Pernas Inquietas , Síndrome das Pernas Inquietas/tratamento farmacológico , Humanos , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Pramipexol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tetra-Hidronaftalenos/uso terapêutico , Tetra-Hidronaftalenos/efeitos adversos , Sono REM/efeitos dos fármacos , Indóis , Tiofenos
2.
BMC Psychiatry ; 24(1): 349, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730422

RESUMO

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.


Assuntos
Cloridrato de Duloxetina , Pramipexol , Síndrome das Pernas Inquietas , Idoso , Feminino , Humanos , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Cloridrato de Duloxetina/efeitos adversos , Fenótipo , Pramipexol/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/induzido quimicamente , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico
3.
J Affect Disord ; 356: 586-596, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657764

RESUMO

BACKGROUND: Diabetes mellitus (DM) is frequently associated with the occurrence and development of depression, and the co-occurrence of diabetes mellitus with depression (DD) may further reduce patients' quality of life. Recent research indicates that dopamine receptors (DRs) play a crucial role in immune and metabolic regulation. Pramipexole (PPX), a D2/3R agonist, has demonstrated promising neuroprotective and immunomodulatory effects. Nevertheless, the therapeutic effects and mechanisms of action of PPX on DM-induced depression are not clear at present. METHODS: Depression, DM, and DD were induced in a rat model through a combination of a high-fat diet (HFD) supplemented with streptozotocin (STZ) and chronic unpredictable mild stress (CUMS) combined with solitary cage rearing. The pathogenesis of DD and the neuroprotective effects of DRs agonists were investigated using behavioral assays, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, Nissl staining, Western blotting (WB) and immunofluorescence (IF). RESULTS: DD rats exhibited more severe dopaminergic, neuroinflammatory, and neuroplastic impairments and more pronounced depressive behaviors than rats with depression alone or DM. Our findings suggest that DRs agonists have significant therapeutic effects on DD rats and that PPX improved neuroplasticity and decreased neuroinflammation in the hippocampus of DD rats while also promoting DG cell growth and differentiation, ultimately mitigating depression-like behaviors. LIMITATION: Our study is based on a rat model. Further evidence is needed to determine whether the therapeutic effects of PPX apply to patients suffering from DD. CONCLUSIONS: Neuroinflammation mediated by damage to the dopaminergic system is one of the key pathogenic mechanisms of DD. We provide evidence that PPX has a neuroprotective effect on the hippocampus in DD rats and the mechanism may involve the inhibition of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation by DRs to attenuate the neuroinflammatory response and neuroplasticity damage.


Assuntos
Depressão , Diabetes Mellitus Experimental , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Plasticidade Neuronal , Pramipexol , Animais , Pramipexol/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Plasticidade Neuronal/efeitos dos fármacos , Masculino , Inflamassomos/efeitos dos fármacos , Depressão/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Ratos Sprague-Dawley , Doenças Neuroinflamatórias/tratamento farmacológico , Agonistas de Dopamina/farmacologia , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças
4.
Mol Pharm ; 21(5): 2512-2533, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38602861

RESUMO

Parkinson's disease (PD) is a debilitating neurodegenerative disease primarily impacting neurons responsible for dopamine production within the brain. Pramipexole (PRA) is a dopamine agonist that is currently available in tablet form. However, individuals with PD commonly encounter difficulties with swallowing and gastrointestinal motility, making oral formulations less preferable. Microneedle (MN) patches represent innovative transdermal drug delivery devices capable of enhancing skin permeability through the creation of microconduits on the surface of the skin. MNs effectively reduce the barrier function of skin and facilitate the permeation of drugs. The work described here focuses on the development of polymeric MN systems designed to enhance the transdermal delivery of PRA. PRA was formulated into both dissolving MNs (DMNs) and directly compressed tablets (DCTs) to be used in conjunction with hydrogel-forming MNs (HFMNs). In vivo investigations using a Sprague-Dawley rat model examined, for the first time, if it was beneficial to prolong the application of DMNs and HFMNs beyond 24 h. Half of the patches in the MN cohorts were left in place for 24 h, whereas the other half remained in place for 5 days. Throughout the entire 5 day study, PRA plasma levels were monitored for all cohorts. This study confirmed the successful delivery of PRA from DMNs (Cmax = 511.00 ± 277.24 ng/mL, Tmax = 4 h) and HFMNs (Cmax = 328.30 ± 98.04 ng/mL, Tmax = 24 h). Notably, both types of MNs achieved sustained PRA plasma levels over a 5 day period. In contrast, following oral administration, PRA remained detectable in plasma for only 48 h, achieving a Cmax of 159.32 ± 113.43 ng/mL at 2 h. The HFMN that remained in place for 5 days demonstrated the most promising performance among all investigated formulations. Although in the early stages of development, the findings reported here offer a hopeful alternative to orally administered PRA. The sustained plasma profile observed here has the potential to reduce the frequency of PRA administration, potentially enhancing patient compliance and ultimately improving their quality of life. This work provides substantial evidence advocating the development of polymeric MN-mediated drug delivery systems to include sustained plasma levels of hydrophilic pharmaceuticals.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Agulhas , Doença de Parkinson , Pramipexol , Ratos Sprague-Dawley , Pramipexol/administração & dosagem , Pramipexol/farmacocinética , Animais , Ratos , Doença de Parkinson/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Masculino , Absorção Cutânea/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos dos fármacos , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/farmacocinética , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/farmacocinética , Hidrogéis/química
5.
Parkinsonism Relat Disord ; 123: 106560, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38518544

RESUMO

BACKGROUND: This study aimed to verify whether the combined use of Da Dingfengzhu and Western medicine in treating Parkinson's disease (PD) can lead to therapeutic efficacy and symptom alleviation, thereby achieving a complementary and synergistic effect. METHODS: In this study, 158 patients were initially enrolled, with 116 eligible patients randomly divided into a control and an observation group. The control group received levodopa/benserazide and pramipexole, while the observation group received Da Dingfengzhu combined with levodopa/benserazide and pramipexole for 12 weeks. Baseline patient characteristics, adverse reactions, and blood samples were collected at baseline and 12 weeks post-treatment. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess symptom severity at baseline, four weeks into treatment, and 12 weeks post-treatment. RESULTS: Adverse reactions during treatment were similar in both groups, suggesting that the combined therapy in the observation group did not increase adverse effects. Both groups showed improvements in UPDRS scores, with the observation group displaying more significant symptom alleviation at 4 and 12 weeks. Moreover, the observation group exhibited more pronounced increases in serum neurotrophic factor-3 and dopamine levels and greater reductions in oxidative stress and inflammatory response markers. CONCLUSION: In conclusion, the combination of Da Dingfengzhu with levodopa/benserazide and pramipexole for treating PD shows significant clinical potential and is worthy of broader application.


Assuntos
Antiparkinsonianos , Benserazida , Medicamentos de Ervas Chinesas , Levodopa , Doença de Parkinson , Pramipexol , Deficiência da Energia Yin , Humanos , Doença de Parkinson/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Benserazida/farmacologia , Benserazida/administração & dosagem , Levodopa/administração & dosagem , Levodopa/farmacologia , Levodopa/efeitos adversos , Pramipexol/farmacologia , Pramipexol/administração & dosagem , Antiparkinsonianos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Deficiência da Energia Yin/tratamento farmacológico , Combinação de Medicamentos , Quimioterapia Combinada , Avaliação de Resultados em Cuidados de Saúde
6.
Psychopharmacology (Berl) ; 241(7): 1365-1375, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38494550

RESUMO

Motivation allows us to energise actions when we expect reward and is reduced in depression. This effect, termed motivational vigour, has been proposed to rely on central dopamine, with dopaminergic agents showing promise in the treatment of depression. This suggests that dopaminergic agents might act to reduce depression by increasing the effects of reward or by helping energise actions. The aim of the current study was to investigate whether the dopamine agonist pramipexole enhanced motivational vigour during a rewarded saccade task. In addition, we asked whether the effects of pramipexole on vigour differ between reward contingent on performance and guaranteed reward. Healthy adult participants were randomised to receive either pramipexole (n = 19) or placebo (controls n = 18) for 18 days. The vigour of saccades was measured twice, once before the administration of study medication (Time 1) and after taking it for 12-15 days (Time 2). To separate motivation by contingency vs. reward, saccadic vigour was separately measured when (1) rewards were contingent on performance (2) delivered randomly with matched frequency, (3) when reward was guaranteed, (4) when reward was not present at all. Motivation increased response vigour, as expected. Relative to placebo, pramipexole also increased response vigour. However, there was no interaction, meaning that the effects of reward were not modulated by drug, and there was no differential drug effect on contingent vs. guaranteed rewards. The effect of pramipexole on vigour could not be explained by a speed/accuracy trade-off, nor by autonomic arousal as indexed by pupillary dilation. Chronic D2 stimulation increases general vigour, energising movements in healthy adults irrespective of extrinsic reward.


Assuntos
Agonistas de Dopamina , Motivação , Pramipexol , Recompensa , Movimentos Sacádicos , Humanos , Pramipexol/farmacologia , Pramipexol/administração & dosagem , Motivação/efeitos dos fármacos , Movimentos Sacádicos/efeitos dos fármacos , Masculino , Adulto , Feminino , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/administração & dosagem , Adulto Jovem , Método Duplo-Cego , Benzotiazóis/farmacologia , Benzotiazóis/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos
7.
Neuropharmacology ; 248: 109851, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325772

RESUMO

Heightened risk-based decision-making is observed across several neuropsychiatric disorders including schizophrenia, bipolar disorder, and Parkinson's disease, yet no treatments exist that effectively normalize this aberrant behavior. Preclinical risk-based decision-making paradigms have identified the important modulatory roles of dopamine and sex in the performance of such tasks, though specific task parameters may alter such effects (e.g., punishment and reward values). Previous work has highlighted the role of dopamine 2-like receptors (D2R) during performance of the Risk Preference Task (RPT) in male rats, however sex was not considered as a factor in this study, nor were treatments identified that reduced risk preference. Here, we utilized the RPT to determine sex-dependent differences in baseline performance and impact of the D2R receptor agonist pramipexole (PPX), and antagonist sulpiride (SUL) on behavioral performance. Female rats exhibited heightened risk-preference during baseline testing. Consistent with human studies, PPX increased risk-preference across sex, though the effects of PPX were more pronounced in female animals. Importantly, SUL reduced risk-preference in these rats across sexes. Thus, under the task specifications of the RPT that does not include punishment, female rats were more risk-preferring and required higher PPX doses to promote risky choices compared to males. Furthermore, blockade of D2R receptors may reduce risk-preference of rats, though further studies are required.


Assuntos
Dopamina , Caracteres Sexuais , Humanos , Ratos , Feminino , Masculino , Animais , Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Pramipexol/farmacologia , Receptores Dopaminérgicos , Tomada de Decisões , Recompensa
8.
Transl Psychiatry ; 14(1): 86, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336862

RESUMO

Impulse control disorders (ICDs), a wide spectrum of maladaptive behaviors which includes pathological gambling, hypersexuality and compulsive buying, have been recently suggested to be triggered or aggravated by treatments with dopamine D2/3 receptor agonists, such as pramipexole (PPX). Despite evidence showing that impulsivity is associated with functional alterations in corticostriatal networks, the neural basis of the exacerbation of impulsivity by PPX has not been elucidated. Here we used a hotspot analysis to assess the functional recruitment of several corticostriatal structures by PPX in male rats identified as highly (HI), moderately impulsive (MI) or with low levels of impulsivity (LI) in the 5-choice serial reaction time task (5-CSRTT). PPX dramatically reduced impulsivity in HI rats. Assessment of the expression pattern of the two immediate early genes C-fos and Zif268 by in situ hybridization subsequently revealed that PPX resulted in a decrease in Zif268 mRNA levels in different striatal regions of both LI and HI rats accompanied by a high impulsivity specific reduction of Zif268 mRNA levels in prelimbic and cingulate cortices. PPX also decreased C-fos mRNA levels in all striatal regions of LI rats, but only in the dorsolateral striatum and nucleus accumbens core (NAc Core) of HI rats. Structural equation modeling further suggested that the anti-impulsive effect of PPX was mainly attributable to the specific downregulation of Zif268 mRNA in the NAc Core. Altogether, our results show that PPX restores impulse control in highly impulsive rats by modulation of limbic frontostriatal circuits.


Assuntos
Agonistas de Dopamina , Comportamento Impulsivo , Ratos , Masculino , Animais , Pramipexol/farmacologia , Comportamento Impulsivo/fisiologia , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , RNA Mensageiro
9.
Int Immunopharmacol ; 128: 111514, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38199193

RESUMO

BACKGROUND: Diabetic neuropathy (DN) is a serious microvascular complication and a major cause of morbidity and mortality in diabetes mellitus. It is characterized by neurodegeneration of terminal sensory nerve fibers with subsequent pain, loss of sensation, and paresthesia, thus compromising the quality of life of diabetic patients. It is considered the leading cause of non-traumatic amputations worldwide, reflecting the insufficiency of current therapies. Pramipexole (PPX) is a dopamine receptor agonist used for the treatment of Parkinson's disease. The current study aims to investigate the potential neuroprotective effect of PPX in an experimental model of DN. METHODS: Sprague Dawley rats were randomly assigned into five groups: normal control, Normal + PPX (1 mg/kg) group, STZ control, STZ + PPX (0.25 and 1 mg/kg/day for eight weeks). The neuroprotective effect of PPX in rats was evaluated in terms of sciatic nerve histological alterations, oxidative stress, and protein expression of TLR4/MyD88/IRAK-1/TRAF-6/NF-κB axis and downstream inflammatory mediators. RESULTS: PPX administration ameliorated histopathological signs of neuronal inflammation and apoptosis. Additionally, PPX attenuated STZ-induced sciatic nerve oxidative stress and downregulated neural tissue expression of TLR4, MyD88, IRAK-1, TRAF-6, NF-κB and downstream mediators (TNF-α, IL-1ß and ICAM-1). CONCLUSION: Collectively, the current study sheds light on PPX as a potential protective medication to alleviate neuropathy progression in diabetic patients. PPX neuroprotective effect can be attributed to modulating TLR4/ MyD88/IRAK-1/TRAF-6/ NF-κB axis signaling in nerve tissues with subsequent attenuation of oxidative stress and inflammation.


Assuntos
Neuropatias Diabéticas , Fármacos Neuroprotetores , Pramipexol , Animais , Humanos , Ratos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neuropatias Diabéticas/prevenção & controle , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , NF-kappa B/metabolismo , Estresse Oxidativo , Pramipexol/farmacologia , Pramipexol/uso terapêutico , Qualidade de Vida , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo
10.
Neurol Sci ; 45(1): 171-175, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37581771

RESUMO

OBJECTIVE: This study aims to clinically evaluate the impulse control disorders (ICDs) encountered in treating Parkinson's disease. METHOD: This is a retrospective analysis between 2010 and 2022. We retrieved the medical records of all patients diagnosed with idiopathic Parkinson's disease. The demographic and clinical findings were recorded. ICDs constituted a specific item in the examination, and each one (compulsive shopping, compulsive eating, pathological gambling, hypersexuality, punding, dopamine dysregulation syndrome, and hobbyism) was noted separately. RESULTS: In the study period, we identified 1824 patients (56.2% men, n = 1025). The mean age was 70.5 ± 11.9 years. In the cohort, 128 (7%) patients with Parkinson's disease had one or more ICDs. The ICDs were compulsive shopping, punding/hobbyism, compulsive eating, hypersexuality, pathological gambling, and dopamine dysregulation syndrome. When we compared patients with and without ICDs, patients with ICDs were younger (p ≤ 0.001), and the men/women ratio was higher in this group with ICDs. Although the mean daily pramipexole dose was higher in patients with ICDs, mean daily long-acting pramipexole dose was only 1.4 ± 0.92 mg/day. CONCLUSION: The significant findings in this study were (i) the lower frequency of ICDs (7%); (ii) the common occurrence of compulsive shopping, punding/hobbyism, and compulsive eating; and (iii) the development of ICDs under relatively lower doses of pramipexole. We suggest that ICDs in Parkinson's disease should be associated with a personal trait with dopamine agonists, and potential electrophysiological or genetic markers of this trait warrant further analysis to avoid treatment in these patients.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta , Doença de Parkinson , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Dopamina , Pramipexol/uso terapêutico , Estudos Retrospectivos , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Agonistas de Dopamina/efeitos adversos , Síndrome
11.
Biol Psychiatry ; 95(3): 286-296, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37330165

RESUMO

BACKGROUND: Dopamine D2-like agonists show promise as treatments for depression. They are thought to act by enhancing reward learning; however, the mechanisms by which they achieve this are not clear. Reinforcement learning accounts describe 3 distinct candidate mechanisms: increased reward sensitivity, increased inverse decision-temperature, and decreased value decay. As these mechanisms produce equivalent effects on behavior, arbitrating between them requires measurement of how expectations and prediction errors are altered. We characterized the effects of 2 weeks of the D2-like agonist pramipexole on reward learning and used functional magnetic resonance imaging measures of expectation and prediction error to assess which of these 3 mechanistic processes were responsible for the behavioral effects. METHODS: Forty healthy volunteers (50% female) were randomized to 2 weeks of pramipexole (titrated to 1 mg/day) or placebo in a double-blind, between-subject design. Participants completed a probabilistic instrumental learning task before and after the pharmacological intervention, with functional magnetic resonance imaging data collected at the second visit. Asymptotic choice accuracy and a reinforcement learning model were used to assess reward learning. RESULTS: Pramipexole increased choice accuracy in the reward condition with no effect on losses. Participants who received pramipexole had increased blood oxygen level-dependent response in the orbital frontal cortex during the expectation of win trials but decreased blood oxygen level-dependent response to reward prediction errors in the ventromedial prefrontal cortex. This pattern of results indicates that pramipexole enhances choice accuracy by reducing the decay of estimated values during reward learning. CONCLUSIONS: The D2-like receptor agonist pramipexole enhances reward learning by preserving learned values. This is a plausible mechanism for pramipexole's antidepressant effect.


Assuntos
Agonistas de Dopamina , Recompensa , Humanos , Feminino , Masculino , Pramipexol , Agonistas de Dopamina/farmacologia , Aprendizagem , Reforço Psicológico
12.
Neurol Sci ; 45(4): 1399-1408, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38079019

RESUMO

BACKGROUND: This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG). METHODS: We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed. RESULTS: This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07-5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77-5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP. CONCLUSION: The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta , Indóis , Doença de Parkinson , Tetra-Hidronaftalenos , Tiofenos , Humanos , Pramipexol/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Agonistas de Dopamina/efeitos adversos , Antiparkinsonianos/efeitos adversos
13.
Eur J Neurol ; 31(2): e16144, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37955562

RESUMO

BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. METHODS: Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case-control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. RESULTS: Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax ) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. CONCLUSIONS: The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta , Doença de Parkinson , Humanos , Agonistas de Dopamina/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/diagnóstico , Pramipexol/uso terapêutico , Estudos de Casos e Controles , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Transtornos Disruptivos, de Controle do Impulso e da Conduta/tratamento farmacológico
14.
Mov Disord ; 39(2): 350-359, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37886872

RESUMO

BACKGROUND: There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity. OBJECTIVES: The objective was to determine if P2B001 (a fixed, low-dose, extended-release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole-ER. METHODS: This was a 12-week, double-blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or commercial doses of pramipexole-ER titrated to optimal dose (1.5-4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole-ER. RESULTS: P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were -2.66 (95% CI, -4.33 to -1.00) versus pramipexole-ER 0.6 mg (P = 0.0018) and - 3.30 (95% CI, -4.96 to -1.63) versus rasagiline-ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole-ER (mean, 3.2 mg), but significantly less worsening in daytime-sleepiness (ESS treatment difference: -2.66 [95% CI, -3.50 to -1.81]; P < 0.0001). P2B001 was well-tolerated with fewer sleep-related and dopaminergic adverse events than titrated doses of pramipexole-ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects. CONCLUSIONS: P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole-ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once-daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Indanos , Doença de Parkinson , Humanos , Pramipexol , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Sonolência , Benzotiazóis/uso terapêutico , Método Duplo-Cego
15.
CNS Neurosci Ther ; 30(4): e14531, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37983933

RESUMO

AIMS: This study aimed to systematically compare the effectiveness, safety, and costs of different anti-Parkinson drugs (APDs). METHODS: This is a multi-center study that retrospectively analyzed the data of 8420 outpatients with PD from 2014 to 2019 across 30 tertiary hospitals in China. The effectiveness was evaluated by changes in total dosages of APDs, normalized by levodopa equivalent dose (LED) and presented as ΔLEDs; levodopa equivalent dose cost (LEDc) represented the daily cost of APDs; and newly added diagnostics were represented as APDs-related adverse events. RESULTS: A total of 384 patients with eligible medical records for three consecutive years were enrolled. Patients treated with carbidopa/levodopa or levodopa/benserazide had significantly lower mean ΔLEDs than other groups (p < 0.01), followed by pramipexole and selegiline. The piribedil group had the highest ΔLEDs, with mean differences of 112.56-355.04 mg compared to other groups (p < 0.01). Meanwhile, LEDc in the levodopa/benserazide, carbidopa/levodopa, and piribedil groups were significantly lower than those in pramipexole or selegiline groups ($0.088-0.135/day for levodopa/benserazide; $0.070-0.126/day for carbidopa/levodopa; $0.112-0.138/day for piribedil; $0.290-0.332/day for pramipexole; $0.229-0.544/day for selegiline; p < 0.01). Patients with piribedil had more adverse events, with an incidence rate of 35.7%, followed by levodopa/benserazide (25.6%), selegiline (23.5%), carbidopa/levodopa (23.3%), and pramipexole (16.4%). Pramipexole showed a lower incidence rate of adverse events than piribedil, including neuropsychiatric symptoms (p = 0.006), headache/dizziness (p = 0.016), and gastrointestinal symptoms (p = 0.031). CONCLUSIONS: Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms.


Assuntos
Levodopa , Doença de Parkinson , Humanos , Levodopa/efeitos adversos , Carbidopa/efeitos adversos , Benserazida/efeitos adversos , Estudos Retrospectivos , Pramipexol/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Piribedil/uso terapêutico , Selegilina/uso terapêutico , Tontura/induzido quimicamente , Tontura/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Cefaleia/induzido quimicamente , Cefaleia/tratamento farmacológico
17.
BMJ Open ; 13(11): e076900, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38035737

RESUMO

INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study. METHODS AND ANALYSIS: Eighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05355337 and NCT05825235.


Assuntos
Anedonia , Depressão , Humanos , Pramipexol/uso terapêutico , Suécia , Depressão/tratamento farmacológico , Seguimentos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Prog Neurobiol ; 231: 102536, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37805096

RESUMO

Excessive daytime sleepiness (EDS) and sleep fragmentation are often observed in Parkinson's disease (PD) patients and are poorly understood despite their considerable impact on quality of life. We examined the ability of a neurotoxin-based mouse model of PD to reproduce these disorders and tested the potential counteracting effects of dopamine replacement therapy. Experiments were conducted in female mice with a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, leading to the loss of dopamine neurons projecting to the dorsal and ventral striatum. Sham-operated mice were used as control. Electroencephalographic and electromyographic recording was used to identify and quantify awaken, rapid eye movement (REM) and non-REM (NREM) sleep states. PD mice displayed enhanced NREM sleep and reduced wakefulness during the active period of the 24-hour circadian cycle, indicative of EDS. In addition, they also showed fragmentation of NREM sleep and increased slow-wave activity, a marker of sleep pressure. Electroencephalographic analysis of the PD model also revealed decreased density and increased length of burst-like thalamocortical oscillations (spindles). Treatment of PD mice with the dopamine receptor agonist, pramipexole, but not with L-DOPA, counteracted EDS by reducing the number, but not the length, of NREM sleep episodes during the first half of the active period. The present model recapitulates some prominent PD-related anomalies affecting sleep macro- and micro-structure. Based on the pharmacological profile of pramipexole these results also indicate the involvement of impaired dopamine D2/D3 receptor transmission in EDS.


Assuntos
Doença de Parkinson , Transtornos do Sono-Vigília , Humanos , Feminino , Camundongos , Animais , Doença de Parkinson/tratamento farmacológico , Dopamina , Pramipexol/farmacologia , Pramipexol/uso terapêutico , Qualidade de Vida , Sono , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia , Modelos Animais de Doenças
20.
PeerJ ; 11: e16039, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719118

RESUMO

Spinal cord injury (SCI) has emerged as a prevalent condition with limited effective treatment options. The neuroprotective role of pramipexole (PPX) in inhibiting nerve cell apoptosis in central nervous system injuries is well established. Therefore, we investigated the effects of PPX in SCI. Adult Sprague-Dawley rats were divided into four groups (sham, SCI, PPX-0.25, and PPX-2.0 groups) according to the PPX therapy (n = 24). Then, SCI was induced using the modified Allen method, and PPX was intravenously administered into the tail at dosages of 0.25 or 2.0 mg/kg following the injury. Motor function was evaluated using the Rivlin-modified inclined plate apparatus and the Basso Beattie Bresnahan (BBB) workout scale. Western blotting assay was used to measure protein expression levels of DRD2, NeuN, Bax/Bcl-2, and caspase-3. Furthermore, immunohistochemistry assessed the effect of PPX on the quantity of NeuN-positive cells in the spinal cord tissue after SCI. Our findings revealed that the BBB and slanting board test scores of the PPX-treated model groups were considerably higher for the SCI group and significantly lower for the sham operation group (P < 0.001). Moreover, the PPX-2.0 group exhibited significantly higher NeuN expression levels than the SCI group (P < 0.01). Our findings indicate that PPX exerts a neuroprotective effect in secondary neuronal injury following SCI, facilitating the recovery of hind limb function by downregulating Bax/Bcl-2, caspase-3, and IL-1ß.


Assuntos
Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Ratos , Animais , Fármacos Neuroprotetores/farmacologia , Caspase 3/genética , Pramipexol/farmacologia , Proteína X Associada a bcl-2 , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/tratamento farmacológico
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