A2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable?

The A2A adenosine receptor (A2AAR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A2AAR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A2AAR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.

Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.

Background: The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS. Objective: To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia. Methods: Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor. Results: The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C. Conclusion: Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.

Prescription pattern and awareness of disease and treatment in patients of Parkinson's disease.

AIM: This cross-sectional study aimed to evaluate the prescription pattern, awareness of disease and treatment in patients with Parkinson's disease (PD). MATERIALS & METHODS: A total of 100 PD patients, attending a tertiary care hospital in Mumbai were included. Prescriptions were analyzed and awareness was evaluated using a questionnaire. RESULTS: The mean number of anti-Parkinson agents (APA) prescribed was 1.52 ± 0.65. Number of APA strongly correlated with disease duration (ρ = 0.818; p < 0.001). Many APA were underutilized (prescribed daily dose/defined daily dose < 1). There was no awareness of all items on symptoms and alternative therapeutic options. Awareness of disease impairments (32%), long-term complications (28%), dosing regimen (46%) and follow-up (36%) was poor. CONCLUSION: More than one APA is commonly prescribed in PD patients. Awareness of disease and treatment of PD is poor among the patients.

Spending trends on neuropsychiatric drugs in Minas Gerais, Brazil: is the offer of anti-parkinson drugs increasing? / Tendência nos gastos com medicamentos neuropsiquiátricos em Minas Gerais, Brasil: há aumento da oferta de antiparkinsonianos

Medicamentos neuropsiquiátricos são utilizados para variadas condições neurológicas e psiquiátricas. O objetivo deste artigo é analisar evolução e determinantes dos gastos públicos com esses medicamentos em Minas Gerais de 2010 a 2017. Dados do Sistema Integrado de Administração de Materiais e Serviços (SIAD) foram usados para estimar volumes de aquisição e gastos. Realizou-se análise de decomposição e, para os medicamentos antiparkinsonianos foi avaliado o elenco adquirido, aplicando-se, ainda, a técnica de Drug Utilization (DU90%). O gasto anual diminuiu 36%, passando de R$ 111,7 milhões em 2010 para R$ 40,9 milhões em 2017, tendo como fatores determinantes a queda de preços e de volume, associada às mudanças do drugmix, optando-se pela aquisição de produtos, em média, mais caros. Destaca-se o aumento dos gastos para a classe dos antiparkinsonianos, porém, com significativa mudança no elenco adquirido. Esse estudo contribuiu para um melhor entendimento dos gastos públicos com medicamentos neuropsiquiátricos. A redução do volume pode elevar o risco de desabastecimento. Com relação aos antiparkinsonianos, não há evidências que sugiram aumento da oferta para a população.

Spending trends on neuropsychiatric drugs in Minas Gerais, Brazil: is the offer of anti-parkinson drugs increasing? / Tendência nos gastos com medicamentos neuropsiquiátricos em Minas Gerais, Brasil: há aumento da oferta de antiparkinsonianos?

Medicamentos neuropsiquiátricos são utilizados para variadas condições neurológicas e psiquiátricas. O objetivo deste artigo é analisar evolução e determinantes dos gastos públicos com esses medicamentos em Minas Gerais de 2010 a 2017. Dados do Sistema Integrado de Administração de Materiais e Serviços (SIAD) foram usados para estimar volumes de aquisição e gastos. Realizou-se análise de decomposição e, para os medicamentos antiparkinsonianos foi avaliado o elenco adquirido, aplicando-se, ainda, a técnica de Drug Utilization (DU90%). O gasto anual diminuiu 36%, passando de R$ 111,7 milhões em 2010 para R$ 40,9 milhões em 2017, tendo como fatores determinantes a queda de preços e de volume, associada às mudanças do drugmix, optando-se pela aquisição de produtos, em média, mais caros. Destaca-se o aumento dos gastos para a classe dos antiparkinsonianos, porém, com significativa mudança no elenco adquirido. Esse estudo contribuiu para um melhor entendimento dos gastos públicos com medicamentos neuropsiquiátricos. A redução do volume pode elevar o risco de desabastecimento. Com relação aos antiparkinsonianos, não há evidências que sugiram aumento da oferta para a população.

Tendência nos gastos com medicamentos neuropsiquiátricos em Minas Gerais, Brasil: há aumento da oferta de antiparkinsonianos? / Spending trends on neuropsychiatric drugs in Minas Gerais, Brazil: is the offer of anti-parkinson drugs increasing?

Resumo Medicamentos neuropsiquiátricos são utilizados para variadas condições neurológicas e psiquiátricas. O objetivo deste artigo é analisar evolução e determinantes dos gastos públicos com esses medicamentos em Minas Gerais de 2010 a 2017. Dados do Sistema Integrado de Administração de Materiais e Serviços (SIAD) foram usados para estimar volumes de aquisição e gastos. Realizou-se análise de decomposição e, para os medicamentos antiparkinsonianos foi avaliado o elenco adquirido, aplicando-se, ainda, a técnica de Drug Utilization (DU90%). O gasto anual diminuiu 36%, passando de R$ 111,7 milhões em 2010 para R$ 40,9 milhões em 2017, tendo como fatores determinantes a queda de preços e de volume, associada às mudanças do drugmix, optando-se pela aquisição de produtos, em média, mais caros. Destaca-se o aumento dos gastos para a classe dos antiparkinsonianos, porém, com significativa mudança no elenco adquirido. Esse estudo contribuiu para um melhor entendimento dos gastos públicos com medicamentos neuropsiquiátricos. A redução do volume pode elevar o risco de desabastecimento. Com relação aos antiparkinsonianos, não há evidências que sugiram aumento da oferta para a população.

Abstract Neuropsychiatric drugs are used for a wide variety of neurological and psychiatric conditions. This article aims to analyze the trend and determinants of public expenditure of these medicines in Minas Gerais, from 2010 to 2017. Data from the Integrated Materials and Services Administration System (SIAD) database were used to estimate volumes of acquisition and expenditure. A breakdown analysis was performed, and the list of purchased drugs was reviewed, and the Drug Utilization technique (DU90%) applied concerning anti-Parkinson drugs. Annual expenditure dropped by 36%, from R$ 111.7 million in 2010 to R$ 40.9 million in 2017, and the determinant factors were the falling prices and volume, associated with changes in the drug mix, which favored the acquisition, on average, of more expensive products. Higher levels of expenditure for anti-Parkinson drugs stand out, however, with a significant change in the list purchased. This study contributed to a better understanding of public spending on neuropsychiatric drugs. A reduced volume can increase the risk of shortages. Regarding anti-Parkinson drugs, there is no evidence to suggest an increased supply to the population.