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1.
Med Res Rev ; 44(5): 2078-2111, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38530106

RESUMO

As the world population ages, there will be an increasing need for effective therapies for aging-associated neurodegenerative disorders, which remain untreatable. Dementia due to Alzheimer's disease (AD) is one of the leading neurological diseases in the aging population. Current therapeutic approaches to treat this disorder are solely symptomatic, making the need for new molecular entities acting on the causes of the disease extremely urgent. One of the potential solutions is to use compounds that are already in the market. The structures have known pharmacokinetics, pharmacodynamics, toxicity profiles, and patient data available in several countries. Several drugs have been used successfully to treat diseases different from their original purposes, such as autoimmunity and peripheral inflammation. Herein, we divulge the repurposing of drugs in the area of neurodegenerative diseases, focusing on the therapeutic potential of antineoplastics to treat dementia due to AD and dementia. We briefly touch upon the shared pathological mechanism between AD and cancer and drug repurposing strategies, with a focus on artificial intelligence. Next, we bring out the current status of research on the development of drugs, provide supporting evidence from retrospective, clinical, and preclinical studies on antineoplastic use, and bring in new areas, such as repurposing drugs for the prion-like spreading of pathologies in treating AD.


Assuntos
Doença de Alzheimer , Antineoplásicos , Demência , Reposicionamento de Medicamentos , Humanos , Doença de Alzheimer/tratamento farmacológico , Animais , Demência/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Estudos Observacionais como Assunto , Avaliação Pré-Clínica de Medicamentos
2.
Epigenomics ; 15(1): 21-38, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36919681

RESUMO

Background: The choice of efficient antipsychotic therapy for schizophrenia relies on a time-consuming trial-and-error approach, whereas the social and economic burdens of the disease call for faster alternatives. Material & methods: In a search for predictive biomarkers of antipsychotic response, blood methylomes of 28 patients were analyzed before and 4 weeks into risperidone therapy. Results: Several CpGs exhibiting response-specific temporal dynamics were identified in otherwise temporally stable methylomes and noticeable global response-related differences were observed between good and bad responders. These were associated with genes involved in immunity, neurotransmission and neuronal development. Polymorphisms in many of these genes were previously linked with schizophrenia etiology and antipsychotic response. Conclusion: Antipsychotic response seems to be shaped by both stable and medication-induced methylation differences.


The most common way to treat schizophrenia is antipsychotic medication. However, not all antipsychotics work for all patients. The only way to find a suitable antipsychotic is to prescribe one and wait, sometimes for months, to see if it works. Finding an alternative to this trial-and-error method would help reduce patient suffering and costs for healthcare systems. The idea is to look in the DNA of our blood cells for specific marks that can change in response to our lifestyle or health condition. These marks could help us predict how patients will react to the drug. In other words, they can serve as biomarkers of antipsychotic response. The current work examined the blood of schizophrenia patients before and 4 weeks after starting medication. The patients who did not respond well to the drug had different marks on the genes involved in immune defense and nervous system functioning. Some of these genes also play roles in the development of schizophrenia, whereas others can directly affect what happens to the drug in the patient's body. Although marks that predict how patients will react were not identified with certainty, valuable targets for future research were identified.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Risperidona/farmacologia , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Metilação de DNA , Benzodiazepinas
3.
Pharmacogenomics ; 24(3): 123-129, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36786192

RESUMO

The Indo-Swiss symposium on pharmacogenomic strategies for the implementation of personalized medicine was conducted as part of the Jawaharlal Institute of Postgraduate Medical Education and Research Integrated Pharmacogenomics Program in Puducherry, India, on 19 November 2022. The symposium was conducted in hybrid mode. The theme of symposium was the impact of pharmacogenomics on the achievement of personalized medicine/precision medicine in the clinical setting. The symposium sought to promote interaction among the participants to initiate future collaborative research projects. The symposium also served as a platform for young researchers to present their research findings as posters to the audience.


Assuntos
Educação Médica , Medicina de Precisão , Humanos , Farmacogenética/educação , Índia
4.
Fundam Clin Pharmacol ; 33(3): 355-364, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30332506

RESUMO

Treatment response to antipsychotic drugs is variable and conflicting results have been obtained while studying the influence of DRD2 and HTR2 genetic variants on antipsychotic drug efficacy. To explore further, the present study aimed to assess the influence of DRD2 -141 C Ins/Del, Taq1A and HTR2A -1438 G/A, 102T/C and HTR2C -759 C/T genetic polymorphisms in response to risperidone in patients with schizophrenia. The study was conducted among the n = 320 South Indian patients with schizophrenia who received risperidone treatment (4-8 mg per day) for a minimum of four weeks. Genotyping was done by real-time PCR. Antipsychotic response was assessed using CGI-I score in cross-sectional group, PANSS score in prospective group at baseline and after receiving the risperidone therapy. DRD2 -141 C Ins/Del (n = 310, Ins/Ins = 177, Ins/Del+ Del/Del = 133, OR 0.70, 95% CI 0.4-1.2 p 0.2), Taq1A (n = 320, AA = 35, AG = 132, GG = 153, p 0.2), HTR2A -1438 G/A (n = 320, AA = 39, AG = 164, GG = 117, p 0.2), HTR2A 102T/C (n = 320, CC = 115, CT = 165, TT = 40, p 0.1) HTR2C -759 C/T (females n = 132, CC = 65, CT+TT = 67, OR 1.3, 95% CI 0.6-2.8, p 0.5; males n = 186, C = 120, T = 66, OR 1.2, 95% CI 0.6-2.4, p 0.4) genetic polymorphisms did not show any association with antipsychotic response to risperidone. DRD2 -141 C Ins/Del, Taq1A, HTR2A -1438 G/A, 102T/C and HTR2C -759 C/T genetic variants are not associated with antipsychotic response to risperidone.


Assuntos
Antipsicóticos/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Estudos Transversais , Feminino , Genótipo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Reação em Cadeia da Polimerase em Tempo Real , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2C de Serotonina/genética , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Resultado do Tratamento , Adulto Jovem
5.
J Pharmacol Pharmacother ; 8(1): 28-32, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28405133

RESUMO

OBJECTIVE: To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 - 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C -759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia. MATERIALS AND METHODS: The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4-8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively. RESULTS: Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 - 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29-84.89, P = 0.004). No such association was observed with 5HTR2C (-759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms. CONCLUSION: Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 - 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.

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