Central nervous system agents in medicinal chemistry最新文献

Introduction: Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins.

Methods: In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí.

Results: Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function.

Conclusion: This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

Objective: The present study was designed to investigate the potential of Pistacia vera (P. vera) fruits in experimental memory impairments in mice.

Material & methods: Memory impairment was induced in Swiss Albino mice by scopolamine (0.4mg mg/kg. i.p). Animals were divided into five separate groups of six animals each, positive control group received carboxy methyl cellulose (CMC) as vehicle, negative control group received scopolamine with vehicle, and standard group received donepezil (5mg/kg i.p) with Scopolamine. Ethanolic extract of P. vera (EEPV) at doses of 200mg/kg & 400mg/kg p.o were administered to group test1 & test 2 respectively along with scopolamine. Elevated plus maze (EPM), passive avoidance paradigms and morris water maze (MWM) were used as exteroceptive behavioral models to access learning and memory activity. Transfer latency, step down latency and escape latency parameters were evaluated plus maze, passive avoidance paradigm, morris water maze. Thereafter lipid peroxidation test, glutathione level and catalase activities were estimated in homogenized brain of mice.

Results: Pretreatment of mice with EEPV (200mg/kg & 400mg/kg) significantly reduced scopolamine induced amnesia. The obtained data clearly revealed that there was increase in escape latency in MWM and also increase in step down latency in passive avoidance paradigm. Transfer latencey was found to be decrease in EPM and biochemical. Parameters were clearly satisfied the data as compared to negative control group which was indicative of cognitive improvement.

Conclusion: P. vera fruit extract demonstrated to improve cognitive process by enhancing memory in different experimental paradigm such as EPM, passive avoidance and MWM when administered orally. Hence it would be worthwhile to explore the potential of this plant in the management of memory disorders.

Background: Brain is the most sensitive organ, whereas brainstem is the most important part of Central Nervous System (CNS). It connects the brain and the spinal cord. However, a myriad of drugs and chemicals affects CNS with severe resultant effects on the brainstem.

Methods: In view of this, a number of literature were assessed for information on the most sensitive part of brain, drugs and chemicals that act on the brainstem and clinical benefit and risk assessment of such drugs and chemicals.

Results: Findings have shown that brainstem regulates heartbeat, respiration and because it connects the brain and spinal cord, all the drugs that act on the spinal cord may overall affect the systems controlled by the spinal cord and brain. The message is sent and received by temporal lobe, occipital lobe, frontal lobe, parietal lobe and cerebellum.

Conclusion: Hence, the chemical functional groups of the brainstem and drugs acting on brainstem are complementary, and may produce either stimulation or depression of CNS.

Introduction: Parkinson's Disease (PD) is one of the most common age-related neurodegenerative disorders which is marked with the loss of dopaminergic neurons. The present study performed on the nose to brain delivery of selegiline hydrochloride loaded nano lipid carrier, suggests that the nasal route is a good mean of targeting the drug directly into the brain.

Methods and materials: Nanostructured lipid carriers were prepared by using hot homogenization. Selegiline hydrochloride loaded NLCs and rotenone treatment were given at a dose of 10 mg/kg administered from 14th day to 28th day. Behavioral parameters were determined at 7th, 14th, 21st and 28th day. On the 28th day, animals were sacrificed for biochemical estimation.

Results: The optimized drug loaded NLC formulation has shown 93±5.25% entrapment efficiency and 51.96% loading capacity. Optimized NLCs formulation has shown 70% release within 10 hours and after that, the release of the drug is sustained up to 22 hours (97%). Pharmacological action of the drug was found to restore the behavioral parameters in rotenone-induced rats.

Conclusion: Nano Lipid Carrier (NLCs) therapeutics has emerged as a prominent method for the treatment of Parkinson's Disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy of neurotherapeutics. It is concluded from the studies that, Selegiline HCl loaded nano lipid carrier which was administered through nasal route has the potential to be used in the management therapy of Parkinson's disease.

Natural compounds extracted from organisms and microorganisms are an important resource for the development of drugs and bioactive molecules. Many such compounds have made valuable contributions in diverse fields such as human health, pharmaceutics and industrial applications. Presently, however, research on investigating natural compounds from marine organisms is scarce. This is somewhat surprising considering that the marine environment makes a major contribution to Earth's ecosystems and consequently possesses a vast storehouse of diverse marine species. Interestingly, of the marine bioactive natural compounds identified to date, many are venoms, coming from Cnidarians (jellyfish, sea anemones, corals). Cnidarians are therefore particularly interesting marine species, producing important biological compounds that warrant further investigation for their development as possible therapeutic agents. From an experimental aspect, this review aims to emphasize and update the current scientific knowledge reported on selected biological activity (antiinflammatory, antimicrobial, antitumoral, anticoagulant, along with several less studied effects) of Cnidarian venoms/extracts, highlighting potential aspects for ongoing research towards their utilization in human therapeutic approaches.

Background: Dual-acting human monoamine oxidase B (hMAO-B) and cholinesterase (ChE) inhibitors are more effective than the classic one-drug one-target therapy for Alzheimer's disease (AD).

Methods: The ChE inhibitory ability of some halogenated thiophene chalcone-based molecules known to be selective hMAO-B inhibitors was evaluated.

Results: Based on the IC50 values, the selected compounds were found to moderately inhibit ChE, with IC50 values in the range of 14-70 µM. Among the synthesised molecules, T8 and T6 showed the most potent inhibitory activity against AChE and BChE, respectively.

Conclusion: Taken together, the data revealed that T8 could be further optimized to enhance its AChE inhibitory activity.