Central nervous system agents in medicinal chemistry最新文献

Background: The most prominent adipokine, adiponectin (APN), has an adverse relationship with the malfunction of adipose tissue. Obesity causes a decrease in plasma APN levels, which eventually results in insulin resistance and diabetes. In this study, we assessed how the effects of APN on memory are influenced by the insulin receptor substrate-1 (IRS-1) and the mammalian target of rapamycin (mTOR) pathways.

Methods: Streptozotocin (STZ) 3 mg/kg intracerebroventricular injections on days 1 and 3 following cannulation were used to create an animal model of Alzheimer's disease. The acquisition phase was preceded by injections of MHY and adiponectin. For the passive avoidance task, the stepthrough latency and total duration in the dark compartment were recorded and evaluated, and the preference index was calculated for the novel object identification test. IRS-1 protein expression in the hippocampus was assessed by western blotting.

Results: STZ reduced the step-through latency (STL), which rose significantly (P≤0.001) in the APN+STZ group. The memory-improving effects of APN were reversed when MHY was administered first (P≤0.001). The STZ and APN+STZ+MHY groups both had a substantial decline in the preference index (P≤0.01). Compared to the control group, the STZ group's expression of the IRS- 1 protein was dramatically reduced (P≤0.0001). In contrast to the APN+STZ group, the MHYtreated group likewise showed decreased IRS-1 protein expression (P≤0.0001), but APN+STZ was able to enhance IRS-1 expression rate (P≤0.0001).

Conclusion: In a rat model of AD, we found that adiponectin improved aversive and cognitive memory, which is at least partially mediated by the mTOR signaling cascade.

Background: Simultaneously with studies on animal models of fetal-induced maternal immune activation, related studies documented behavior, neurophysiological, and/or neurochemical disorders observed in some neuropsychiatric disorders, including autism and schizophrenia.

Objective: To investigate whether treatment tianeptine might ameliorate maternal immune activation (MIA)-induced behavioral deficits in the offspring.

Materials and methods: The pregnant mice were injected through tail vein injection at a concentration of 5 mg/kg of polyriboinosinic-polyribocytidilic acid (polyI:C) and/or used saline as a vehicle. The injection was performed on the 9th day of pregnancy. Each group of MIA offspring was subjected to vehicle, clozapine, or tianeptine treatment.

Results: In prepulse inhibition (PPI) test, oral treatment with tianeptine ameliorated MIA-induced sensorimotor gating deficit. Most behavioral parameters of social interaction test (SIT), forced swimming test (FST), and open field test (OFT) were significantly changed in the MIA offspring. Tianeptine treatment significantly recovered behavioral changes observed in the SIT, OFT, and FST. In order to confirm expression level of neurodevelopmental proteins, immunohistochemical image analysis and Western blot were performed, and the medial prefrontal cortex (mPFC) was targeted. As a result, it was confirmed that the neurodevelopmental proteins were decreased, which was recovered after administration of tianeptine to MIA offspring.

Conclusion: Tianeptine might be useful for treating psychiatric disorders with neurodevelopmental issues.

Background: Oxidative stress is an important contributor to Alzheimer's disease. Olibanum has therapeutic effects on various diseases. The effect of Olibanum on memory deficit induced by scopolamine (Sco) was challenged.

Methods: Four groups were considered as (1) control (2) Sco, (3-4) Sco - Olib 100 and 200 mg/kg. Treatment by Olib or vehicle was done for two weeks. The third week was accompanied by the Morris water maze (MWM) and passive avoidance (PA) with Sco injection. On the last day, the brain and hippocampus were used for evaluation of the malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and a total thiol group.

Results: Sco increased the traveled time and distance to reach the hidden platform during five days of learning (p<0.01 - p<0.001) whereas it decreased the traveled time and distance (p<0.05- p<0.01) in the target area during the probe test of MWM. Sco also decreased delay time in the PA test (P<0.05 - P<0.001). Sco also decreased CAT, SOD, and thiol, whereas it, increased MDA in both the cortex and hippocampus (p<0.01 - p<0.001). Olib attenuated the impaired performance of the rats induced by Sco in MWM and PA tests. Olib reversed the increasing effects of Sco on MDA in both cortex and hippocampus and also reversed the attenuating effects of Sco on CAT, SOD, and thiol.

Conclusion: Olib had an inhibitory effect on memory deficit induced by Sco probably through its anti-oxidant property.

Epilepsy is the most general, extensive, and severe neurological disorder, affecting more than 50 million individuals globally. Initially, conventional medicines and simple salts like potassium bromide were employed as antiepileptic medication candidates. Nowadays, many anticonvulsant drugs have been discovered as first-generation and second-generation and newer drugs and are still in development phases. The pharmacophore-based drug design process includes pharmacophore modeling and validation, pharmacophore-based virtual screening, virtual hits profiling, and lead identification with special reference. This comprehensive article reviews recently developed anticonvulsant derivatives on the basis of pharmacophoric approaches. A literature survey was performed using various search engines like Google Scholar, Scopus, Sci Finder, ScienceDirect, Science gate, Scilit, PubMed, NINDS database of NIH, Bentham Sciences, and other online and print journals and scientific databases. The presented review discusses such kinds of newer drugs that are in the market as well as in clinical trial phases. Detailed outcomes of pharmacophoric modeling have been discussed for newly derived derivatives like targets involved in Epilepsy, lead molecules etc., for the treatment of epilepsy. This exhaustive review will assist the researchers in the further development of potential antiepileptic agents.

Introduction: Mental disorders during pregnancy are one of the major public health problems because of its effect on both mother and child, but the prevalence of psychiatric disorders in infertile women is largely unknown to compare psychiatric disorders during and after pregnancies with assisted reproductive therapies (ART) and spontaneous pregnancies.

Methods: This cross-sectional study was conducted on pregnant women referring to midwifery centers in Ahvaz City in 2022. Pregnant women were included in two groups of either pregnancy caused by ART (n= 84) or spontaneous pregnancy (n= 256). The Symptom Checklist-90-R (SCL90-R) was used to assess psychiatric disorders during and after pregnancies.

Results: A high percentage of women with spontaneous pregnancy (74.6%) and ART (91.7%) had some degree of psychological disorders. The severity of psychological disorders in both groups was higher during pregnancy than after pregnancy (P<0.001). The intensity of various psychological disorders during and after pregnancy in the ART pregnancy group was significantly higher than the control group (P<0.001). An increased risk of psychiatric disorders during pregnancy was associated with the history of psychiatric disorders [odd ratio (OR): 12.393; P= 0.022], family history of psychiatric disorders (OR:26.168; P<0.001), history of infertility (OR: 19.00; P<0.001), primary infertility (OR: 12.714; P=0.004), infertility duration more than three years (OR: 43.424; P<0.001), and frequency of embryo transfer (OR: 18.939; P=0.045).

Conclusion: Psychiatric disorders were prevalent among pregnant women in the study area especially in pregnant women with ART. Regular screening programs for mental health problem should be included in an antenatal care service especially in this high-risk group.

Introduction: Depression is one of the most frequently occurring psychiatric disorders worldwide, affecting 121 million worldwide. World Health Organization (WHO) estimates that it is the leading cause of disability and the fourth leading contributor to the "global burden of diseases".

Objective: Investigating and developing a drug with a novel benefit-risk profile is critical. Marine sources have been explored for their benefits as an alternative therapy for depression treatment. Numerous studies have shown that natural compounds containing peptides, alkaloids, polyphenols, diterpenes, glycosides, vitamins, and minerals from marine sources can potentially treat a wide range of disorders, including depression. Such phytoconstituents are known to reduce oxidative stress and neuroinflammation, regulate the synthesis or function of neurotransmitters such as glutamate and acetylcholinesterase, and aid in enhancing serotonin levels and nerve development.

Methods: In this review study, a literature search was conducted using terms often used, including animal models of depression and their precise phases, marine sources, algae, sponges, and indole alkaloids. Additionally, databases were examined, including Scopus, Wiley, Elsevier, Google Scholar, and Web of Science. The Snowball technique was used to identify several articles about depression but correlated to marine sources in addition to database searches.

Results: Current antidepressant medications have several negative side effects on the human body, including dry mouth, cardiovascular interference, gastrointestinal symptoms, genitourinary symptoms, hepatotoxicity, convulsions, and obesity. As a result, researchers can identify a wide range of potential targets for medications derived from marine sources. A combination of marinederived drugs and available treatments can be estimated to minimize the negative effects. So that these resources can be used as efficiently as possible, and various marine-derived substances can be studied for therapeutic efficacy.

Conclusion: This review focuses on the preclinical and clinical findings of marine-derived compounds with antidepressant properties that alter behavioural parameters and biochemical abnormalities, as well as their mechanism of action and in-vivo potential.

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.