Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) - Volume 23, Issue 1, 2023

Introduction: The brain is the most complex organ in the human body, with a high and constant demand for inputs. Adequate nutrition is essential for the complete functioning of the brain, not only due to the energy supply, mainly from carbohydrates, but also due to the adequate supply of other macronutrients and micronutrients for the synthesis of neurotransmitters and protein components. Vitamins, minerals, and other components of the diet also constitute the so-called “neuro-nutrients”. Objective: It was to develop a systematic review to highlight key neuro-nutrients and clinical studies that direct strategies for adequate nutritional status. Methods: The rules of the Systematic Review-PRISMA Platform were followed. The research was carried out from October 2021 to February 2022 and developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results: A total of 234 articles were found and 167 articles were evaluated in full, and 118 were included and evaluated in the present study. According to the GRADE instrument, most studies (>50%) followed a controlled clinical study model and had a good methodological design. The overall assessment resulted in 54 studies with a high risk of bias to the small sample size. The most important macronutrients in neuro-nutrition are phosphatidylserine and tryptophan. Micronutrients are methyl folate, vitamins B6 and B12, magnesium, arginine, choline, and niacin. Conclusion: The areas of neurology and psychiatry have shown great advances regarding the deepening of knowledge in prophylaxis and pathophysiology, as well as in the treatment of established diseases. The recognition of the role of nutrition as an adjunct to these processes is currently growing. The search in scientific bases for neuro nutrients reveals a great growth of publications related to this theme. In the present text, some of these nutrients were explored to verify the current state of knowledge.

Objectives: Elaeocarpus ganitrus, a member of the Eleocarpaceae family, is valued in Hinduism and Ayurveda, and is frequently used as a remedy for a variety of illnesses. The plant is reputed to treat a number of stomach issues. The purpose of the study was to produce high-quality scientific data regarding gastroprotective behavior, docking experiments with cholinergic receptors, and HPTLC (with lupeol and ursolic acid). To develop the mechanism of herbal extracts, in vitro anticholinergic and antihistaminic activities were evaluated. Different leaf extracts were treated with various reagents to determine the presence of various metabolites. An examination of the histopathology was conducted to determine the full impact of the extract. Methods: Methanolic extract was chosen for HPTLC investigations after extraction with various solvents. A mobile phase of toluene, ethylacetate, and formic acid (8:2:0.1) was chosen. Molecular docking was utilized to examine how ursolic acid and lupeol are bound to cholinergic receptors (M3). Different extracts (aqueous and ethanolic) were tested for their ability to provide gastroprotection in Wistar rats at different doses (200 and 400 mg/kg). Results: Phytochemical analysis of different extracts showed the presence of different primary and secondary metabolites. HPTLC data showed the presence of both standards. Docking studies exhibited very good interactions with the M3 receptor. Pharmacological studies revealed that extract-treated groups significantly reduced the ulcer index in all of the models mentioned above. The histopathological analysis clearly supports the biochemical studies, which were conducted utilizing various doses and found to be effective in a dose-dependent manner. The in vitro analysis proved that the abovementioned extracts may act as antagonists of acetylcholine and histamine. Conclusion: The data obtained would be valuable for the production of the monograph of the plant and conducting concept-related clinical studies in the future. More investigation is required since the gathered scientific data may lead to new research opportunities.

Background: Antidepressant properties of melatonin and atorvastatin have been reported by clinical and experimental studies. Since both melatonin and atorvastatin possess antioxidant properties and considering the involvement of oxidative stress factors in depression, the aim of the present investigation was to study the possible role of oxidative stress factors in the antidepressant- like effect of melatonin and atorvastatin combination in mice forced swimming test. Methods: Following the induction of restraint stress, mice were randomly divided into eight groups including the non-stressed and stressed vehicle-treated groups, melatonin- and atorvastatintreated groups, a combination of melatonin and atorvastatin-treated group, and fluoxetineadministrated group. The open field test (OFT) and forced swimming test (FST) were carried out, and the hippocampus and prefrontal cortex were removed for the measurement of oxidative stress factors. Results: Induction of restraint stress increased the immobility time in FST, and melatonin (10 mg/kg) significantly reduced it. Atorvastatin at both doses of 1 and 10 mg/kg could not alter the immobility time, significantly. Co-administration of melatonin and atorvastatin (10 mg/kg) exerted a significant antidepressant-like response and decreased the immobility time compared with melatonin or atorvastatin (10 mg/kg), alone. Induction of restraint stress elevated the malondialdehyde (MDA) levels in mice's hippocampus, while pretreatment of animals with atorvastatin (10 mg/kg) could reverse it. The co-administration of melatonin and atorvastatin (10 mg/kg) increased the cortical superoxide dismutase (SOD) activity compared with atorvastatin alone, but could not alter the catalase (CAT) activity. Conclusion: It is concluded that atorvastatin might augment the antidepressant-like properties of melatonin in FST.

Background: The most widespread signalling system in the brain is the cholinergic system, which plays a central role in the progress of Alzheimer’s diseases (AD). Current AD treatment primarily targets the neuronal acetylcholinesterase (AChE) enzyme. The finding of AChE activity may play a vital role in optimizing assays for drug discovery of new AChE inhibiting agents. During in-vitro assay of AChE activity, the use of various organic solvents is imperative. Objective: The present study is designed to evaluate the effect of different organic solvents on enzyme activity and enzyme kinetics. Method: Organic solvents' AChE inhibitory potential (including enzyme kinetics: Vmax, Km and Kcat) was evaluated using substrate velocity curve by using non-linear reversion Michaelis-Menten kinetic function. Results: DMSO was found to have the most potent AChE inhibitory effect, followed by acetonitrile and ethanol. The kinetic study revealed DMSO as a mixed inhibitory effect (competitive/noncompetitive manner), ethanol as non-competitive, and acetonitrile as a competitive inhibitor of the AChE enzyme. Methanol has shown a negligible impact on enzyme inhibition and kinetics, suggesting its suitability for the AChE assay. Conclusion: We assume that our study results will help design the experimental protocols and support analyzing investigational outcomes while screening and biological evaluation of new molecules using methanol as solvent/cosolvent.

Background: Convolvulus pluricaulis is a native plant that is commonly mentioned in Ayurveda as a Rasayana and is primarily recommended for use in mental stimulation and rejuvenation therapy. Convolvulus pluricaulis is used as a brain tonic. The plant is reported to be a prominent memory-improving drug. It is used as a psychostimulant and tranquilizer. It is reported to reduce mental tension. Objective: The present study aimed to explore the protective effect of hydroalcoholic extract from the leaves of Convolvulus pluricaulis along with CNS depressant and anti-anxiety activities, in models of mice. Methods: The extract from leaves of Convolvulus pluricaulis were sequentially isolated with a mixture of water and alcohol solution in the soxhlet apparatus. An acute toxicity study was conducted as per OECD guidelines no. 423, in which 18 Albino male mice were treated with different doses (1, 10, 100, 500, 1000, and 2000 mg/kg) of hydroalcoholic extract of Convolvulus pluricaulis and assessed for toxicity parameters for 14 days. Various psychomotor activities of hydroalcoholic extract from leaves of Convolvulus pluricaulis for 100, 200, and 300 mg/kg doses were performed in mice by using various tests like actophotometer, open field, rota-rod, grip strength tests, elevated plus maze, hole board test, inclined plane, chimney test. Results: The hydroalcoholic extract from leaves of Convolvulus pluricaulis was found to fall under category 4 in the acute toxicity study. Therefore, 100, 200, and 300 mg/kg doses of hydroalcoholic extract of leaves of Convolvulus pluricaulis were selected for the further pharmacological study. The results of psychomotor tests (actophotometer, open field, rota-rod, grip strength, hole board test, inclined plane, chimney test, elevated plus maze, light-dark model) for test doses 100, 200, and 300 in mice showed CNS depressant and anti-anxiety effects. Conclusion: Hydroalcoholic extract from leaves of Convolvulus pluricaulis at the 100, 200, and 300 mg/kg doses has shown CNS depressant and anti-anxiety effects in mice models.

Background: Motivated by the exciting biological potential for the use of hybrid molecules in medicine and therapy. It is anticipated that the coumarin-chalcone hybrids for skeletal muscle and antianxiety action will be investigated using a chemical hybridization technique. Objective: Due to its numerous benefits, including high effectiveness, mode of action at receptors, minimal adverse effects, and improved pharmacokinetic features, naturally occurring and synthesized hybrid compounds are prospective sources for novel drug development techniques. In opinion of these applications, we here designed some coumarin-chalcone hybrids and explored them for skeletal muscle and antianxiety potential. Methods: Using a chemical hybridization strategy, coumarin-chalcone hybrids have been synthesized and evaluated for skeletal muscle and antianxiety activity. The target compounds were synthesized by reaction of 7-hydroxy-4-methylcoumarion with haloalkane to afford 7-(2- bromoethoxy)-4-methyl-2H-chromen-2-one which was further treated with hydroxychalcones. The structures of target compounds were confirmed on the basis of their Melting Point, Thin Layer Chromatography, IR, 1HNMR and Mass studies. The computational properties of target compounds were also determined through online software. Skeletal muscle and antianxiety potential were performed in Swiss albino mice. Results: The coumarin-chalcones hybrids showed skeletal muscle and antianxiety potential in Swiss albino mice and computational properties of the target compounds were also showed similarity as compared with diazepam. Conclusion: Among the target compounds, the fluoro group containing compound was found to be more potent as compared to the standard drug diazepam.

Introduction: Toxoplasmosis and narcotic drug addiction are endemic in various regions of Iran. These drugs can provide situations for infections by disrupting the immune system. The current case-control study was designed to determine the prevalence of toxoplasmosis in narcotic drugaddicted persons in comparison with healthy subjects using serology and molecular techniques in the southwest of Iran. Methods: A total of 201 subjects (including 101 individuals with drug addiction and 100 control participants) were randomly selected. Chronic and acute toxoplasmosis was detected using the enzymelinked immunosorbent assay (ELISA) IgG avidity. T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) were also determined by the ELISA. Moreover, the presence of T. gondii in blood samples was diagnosed using the nested-polymerase chain reaction (Nested-PCR). Results: For T. gondii IgG, 17 (17.0%) of 100 and 39 (38.6%) of 101 cases were diagnosed in the control participants and drug-addicted people, respectively [P=0.001, OR=3.071, CI= (1.591-5.929)]. Moreover, 16 (15.8) and 5 (5.0%) cases were positive for the B1 gene in the drug-addicted patients and controls by the nested-PCR technique, respectively [P=0.019, OR=3.576, CI= (1.257-10.179)]. However, no significant differences were found between the opium (n=64) and crystal methamphetamine (n=37) groups in terms of T. gondii IgG and IgM antibodies and the presence of the parasite in the blood (P>0.05). Conclusion: The present results demonstrated that the outbreak of the infection was more frequent in narcotic drug-addicted persons than the controls using serology and molecular techniques.