RESUMO
Parkinson's disease, often known as PD, is a more common age-related neurological disorder that affects a huge number of older adults worldwide. Parkinson's disease is predominantly a movement-related pathosis and is distinguished by the deposition of intra-neuronal aggregates, as the alpha-synuclein gene is expressed as Lewy bodies (LB) causing dopaminergic neurons to die. Stress in early life may contribute to the development of depression, and depression in patients may result in the development of Parkinson's disease as they mature. Depression is a non-motor condition that leads to motor symptoms, such as Parkinson's disease. PD Patients are currently utilizing a variety of other therapies like utilizing nutritional supplements, herbal remedies, vitamins, and massage. When a patient's functional ability is impaired, drug treatment is usually initiated according to the individual's condition and the severity of signs and symptoms. The current marketed anti-Parkinson drugs, has low brain distribution and failing to repair dopaminergic neurons or delaying the progression of the disease these negative effects were unavoidable. To overcome these disadvantages, this review considers the inclusion of drugs used in Parkinson's disease, focusing on strategies to reuse existing compounds to speed up drug development, their capacity to traverse the BBB, and drug dispersion in the brain. We look at cellular therapies and repurposed drugs. We also investigate the mechanisms, effectiveness, as well as safety of several new medications that are being repositioned for Parkinson's disease pharmacotherapy. In this study, we focus on global trends in Parkinson's disease research. We hope to raise awareness about the present state of major factors for disability worldwide, including yearly prevalence's from international and national statistics. The pathophysiology of Parkinsonism and also analyze existing therapies for Parkinson's disease, moreover new and innovative drug therapies, and to assess the prospects for disease modification.
Assuntos
Doença de Parkinson , Humanos , Idoso , Doença de Parkinson/tratamento farmacológico , Encéfalo , Neurônios DopaminérgicosRESUMO
Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation. To enhance the therapeutic efficacy and physical properties of AT and CU, a new conjugate derivative (AT-CU) was synthesized and assessed by in silico, in vitro characterizations, and in vivo efficacy through mice model. Although the biocompatibility and biodegradability of Polylactic-co-Glycolic Acid (PLGA) in nanoparticles are well documented, burst release is a common issue with this polymer. Hence the current work used chitosan as a drug release modifier to the PLGA nanoparticles. The chitosan-modified PLGA AT-CU nanoparticles were prepaid by single emulsion and solvent evaporation technique. With raising the concentration of chitosan the particle size grew from 139.2 nm to 197.7 nm, the zeta potential rose from -20.57 mV to 28.32 mV, and the drug encapsulation efficiency improved from 71.81% to 90.57%. At 18 h, the burst release of AT-CU from PLGA nanoparticles was seen, hitting abruptly 70.8%. For chitosan-modified PLGA nanoparticles, the burst release pattern was significantly reduced which could be due to the adsorption of the drug on the surface of chitosan. The efficiency of the ideal formulation i.e F4 (chitosan/PLGA = 0.4) in treating atherosclerosis was further strongly evidenced by in vivo investigation.
Assuntos
Aterosclerose , Quitosana , Curcumina , Nanopartículas , Animais , Camundongos , Quitosana/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Atorvastatina , Curcumina/química , Cobre , Portadores de Fármacos/química , Glicóis , Nanopartículas/química , Aterosclerose/tratamento farmacológico , Tamanho da PartículaRESUMO
Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role in the pathogenesis and occurrence of Alzheimer's disease. In the present study we evaluated and compared the effect of Captopril and Perindopril against aluminium chloride induced amyloidogenesis and cognitive dysfunction in rats. Wistar rats of both sex were divided randomly into four groups i.e. Group I was served as normal control and treated with normal saline, Group II was administered with AlCl3 (100 mg/kg, p. o.) and Group III and IV received Captopril (30 mg/kg, p. o.) and Perindopril (5 mg/kg, p. o.) respectively 1hr prior to administration of AlCl3. All the doses were given once daily for 42 days. The evaluation of memory function was carried out in Y-maze (spontaneous alternation), radial arm maze (number of correct responses) and elevated plus maze (transfer latency). After behavioral studies, estimation of antioxidant status (brain and serum), amyloid-ß content (brain) and histopathology of brain hippocampus region was done. Administration of AlCl3 for 42 days impaired cognitive dysfunction. Captopril and Perindopril prevented AlCl3 induced cognitive dysfunction by improving spontaneous alternation behavior, number of correct responses and reducing transfer latency. They also increase the antioxidant status, reduce the Aß42 content in the brain and reverse the histopathological changes caused by AlCl3 in hippocampal region. Both Captopril and Perindopril protects against aluminium chloride induced amyloidogenesis and AD like pathology. Captopril is found to be more effective than Perindopril.
RESUMO
Antipyrine (1,2-dihydro-1,5-dimethyl-2-phenylpyrazole-3-one) in a structural frame consists of a five membered lactam pyrazolone heterocyclic ring as a pharmacophore moiety. It is evident from literature that the molecules having nitrogen bearing heterocyclic nuclei clearly exhibit several biological actions. Commercially available pyrazolone derivatives as drugs, analgin and metamizol are an established chemical class of analgesics. Recent trends of synthetic routes and several biological actions of antipyrine analogues are considered in this review. Indeed, the synthesized derivatives possess antipyrine moiety having versatile biological properties, antimicrobial, antitubercular, anthelmintic, antioxidant, analgesic, anti-inflammatory, cytotoxic and antiviral activities.
Assuntos
Analgésicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Analgésicos/química , Animais , Anti-Infecciosos/química , Anti-Inflamatórios/química , Antineoplásicos/química , Antipirina/química , Antipirina/farmacologia , Antituberculosos/química , Humanos , Pirazolonas/química , Pirazolonas/farmacologiaRESUMO
Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central renin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration. Although it has shown promise, clinical efficacy is limited to few drugs including telmisartan mainly due to the poor brain availability of others. In this review we aim to analyze the potential of antioxidants to reduce oxidative stress in brain. We have given critical analysis of the approaches for re-purposing of AT1 blockers against oxidative stress induced neurodegeneration.