ROLE OF DRUG DISCOVERY IN CENTRAL NERVOUS SYSTEM DISORDERS: AN OVERVIEW

Central nervous system (CNS) stimulants are drugs, which produce a response that could be used to alleviate a particular medical condition. These are the agents, which speed up to treat conditions characterized by lack of adrenergic stimulation, including narcolepsy and neonatal apnea. The majority of CNS stimulants is chemically similar to the neurohormone norepinephrine and simulates the traditional "fight or flight" syndrome associated with sympathetic nervous system arousal. A small figure of added members of the CNS stimulant class do not fall into definite chemical groups. The review on central nervous system stimulants gives detail study of CNS stimulant drugs, their mechanism of action and in vivo models of CNS stimulants. The brain is a delicate tissue, and advancement built very effective methods to guard it. Unfortunately, the same mechanisms that protect it against intrusive chemicals can also upset therapeutic interventions. Many current medications are rendered unsuccessful in the treatment of cerebral maladies due to our incapability to efficiently deliver and sustain them within the brain. KEYWORDS: CNS Stimulants, Blood brain barrier (BBB), Drug toxicity, Drug Safety

Diplazium esculentum (Retz.) Sw.: Ethnomedicinal, Phytochemical, and Pharmacological Overview of the Himalayan Ferns

The genus Diplazium (family: Athyriaceae) comprises approximately 350 species of pteridophytes. Diplazium esculentum (Retz.) Sw. is an important member of this genus and commonly known as a wild vegetable in the Himalayan and sub-Himalayan communities. According to the literature analysis, D. esculentum was traditionally used for the prevention or treatment of several diseases such as diabetes, smallpox, asthma, diarrhea, rheumatism, dysentery, headache, fever, wounds, pain, measles, hypertension, constipation, oligospermia, bone fracture, and glandular swellings. Various extracts of D. esculentum were evaluated to elucidate their phytochemical and pharmacological activities. A wide array of pharmacological properties such as antioxidant, antimicrobial, antidiabetic, immunomodulatory, CNS stimulant, and antianaphylactic activities have been recognized in different parts of D. esculentum. The review covers a systematic examination of pharmacognosy, phytochemistry, and pharmacological applications of D. esculentum, but scientifically, it is not fully assessed regarding complete therapeutic effects, toxicity, and safety in the human body. The published literature on D. esculentum and its therapeutic properties were collected from different search engines including Wiley online, PubMed, Springer Link, Scopus, Science Direct, Web of Science, Google Scholar, and ACS publications by using specific terms such as “Diplazium esculentum, bioactive compounds, biological activities and health benefits” from 1984 to 2021 (March). Therefore, further studies are required to identify the detailed action mechanism of D. esculentum in vitro/in vivo, and also, more studies should focus on conservation, cultivation, and sustainable utilization of the species.

Pseudoephedrine—Benefits and Risks

Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.

The Abuse of Central Nervous System Stimulants and its Impact on the Youth of Eastern Nigeria

The class of drugs designated as central nervous system (CNS) stimulants includes the four social drugs that find use among some youth of Eastern Nigeria; caffeine, nicotine, cocaine and marijuana. CNS stimulants increase or enhance the activity of monoamines (such as dopamine and nor epinephrine) in the brain, which leads to increased heart rate, blood pressure, and respiration. They also have a high potential for addiction. Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. It is considered a brain disease because these drugs change the brain structure and function. The aim of this review is to answer the following questions: What are the common types of CNS stimulants abused in Eastern Nigeria? What prompts people to start taking these drugs? Why do people become addicted to these drugs? How does CNS stimulant abuse gain foothold in Eastern Nigeria? What are the implications of this drug taking for the users and the development of youth? How does the abuse of these stimulants affect the Eastern Nigerian society? How can the use of CNS stimulants among youth of eastern Nigeria be prevented or discouraged? Is there any treatment available for the youth addicted to CNS stimulants in Eastern Nigeria?

Citraka (Plumbago zeylanica): A Potential Rejuvenator

Plumbago zeylanica is also known as chitraka, doctor bush, or leadwort. It is the most popular herbal plant that belongs to the family Plumbaginaceae or leadwort. Plumbagin is the most important chemical constituent present in the roots, leaves and stem of the plant that is responsible for various pharmacological actions including anti-malarial, anti-obese, anti-diabetic, anti-microbial, anti-ulcer, anti-inflammatory, anti-oxidant and anti-cancer. Traditionally it is used to treat variety of diseases such as dysmenorrhea, leprosy, anemia, rheumatic pain, cold, cough, arthritis and many more. It is considered as the most significant herbal plant in the ayurveda medicinal system of India and is widely accepted as a rejuvenator because of the presence of bioactive compounds. Various formulations of chitraka plant have made this plant more effective in the field of medicine. The plant carries various therapeutic properties and acts as a cardiotonic, neuroprotective and cns stimulant. The review aim is to provide data or information related to chitraka plant its usage in traditional and ayurveda medicinal system, its pharmacological properties and toxicity when taken in excessive amount. From the collected data, it is clear that the plant has great potential to cure various diseases and needs more research and development to explore its more pharmacological properties and socio-economic impact.

NEUROPHARMACOLOGICAL STUDY OF PHYLLANTHUS NIRURI IN SWISS ALBINO MICE

Objective: The objective of this study is to evaluate the neurological, behavioral, and autonomic changes of Phyllanthus niruri in Swiss albino mice using Irwin’s method. Methods: A total of 24 mice was divided into four groups of six each (3-male, 3-female in each group). Aqueous extract of P. niruri was prepared. Based on body weight aqueous extract was given to the mice by orally through gavage tube (Group I – 300 mg/kg, Group II – 600 mg/kg, Group III – 900 mg/kg, and Group IV – 1200 mg/kg). Neuropharmacological profile is studied for each mice using Irwin’s observational test, the mice were observed for 4 h after oral administration for various behavioral, neurological, and autonomic changes at 0, 1, 2, 3, 4 h. Results: P. niruri showed negligible actions at 300 mg/kg and 600 mg/kg body weight. At 900 mg/kg and 1200 mg/kg P. niruri showed certain behavioral and neuronal changes. P. niruri increased alertness, stereotypy, restlessness, irritability/aggressiveness in behavioral profile indicating that the drug is a CNS stimulant. Furthermore, it showed mild tremors in neurological profile indicating CNS excitation. Conclusion: Aqueous extract of P. niruri at 900 mg/kg and 1200 mg/kg showed changes in behavioral profile, neurological profile, showing it as CNS stimulant properties. Since it is an observational study further research should be done to explore CNS stimulant properties in various in vivo studies.

A Comprehensive Review on Therapeutic Potential of Benzimidazole: A Miracle Scaffold

Background: Benzimidazole is a category of heterocyclic aromatic compounds formed from the fusion of six membered benzene with five membered imidazolering. The moiety possesses diverse biological and clinical applications. A number of studies have shown that a varied substituent around the benzimidazole nucleus results in pharmacologically active compounds of therapeutic interest. Purpose: Owing to its number of pharmacological properties, this moiety is of choice of interest in designing and synthesis of new therapeutic compounds. The existence of the benzimidazole core in numerous groups of biological agents like antimicrobial, antiviral, antiparasitic, antihypertensive, anticancer, CNS stimulant as well as depressants has made important scaffold for development of many newer therapeutic agents. There is utmost need to understand the synthesis and associated role of benzimidazole derived compounds in different diseases. Therefore, in the present review, we attempt to discuss various derivatives of benzimidazole nucleus with different pharmacological activities. Conclusion: Benzimidazoles have played a great role in discovery of drug and development. Huge attempt has been made towards benzimidazole heterocyclic-based organic compounds with great excellence that resulted in drugs with enormous biological activity. Therapeutic drugs containing benzimidazole nucleus are used in building drugs that serve to be an active area of research. This article becomes a source that will lead to discovery of new opportunities for all researchers interested in benzimidazole-based heterocyclic medicinal chemistry.

0774 Factors Associated With The Continuous Use Of Psychotropic Treatments For Narcolepsy

Introduction Narcolepsy is a debilitating disorder characterized by excessive sleepiness and cataplexy episodes. There is no cure for this disease. Current treatments focus on controlling the symptoms with CNS stimulants for sleepiness and antidepressants and/or CNS depressants for cataplexy. This study examines the factors that can contribute to the cessation of narcolepsy treatment. Methods The study includes 291 narcoleptic individuals who were interviewed twice, approximately five to seven years apart, in Wave 1 (W1) and Wave 2 (W2). Telephone interviews were conducted with the help of the Sleep-EVAL system; narcolepsy individuals were initially evaluated and diagnosed by a Sleep Specialist. Results At W1, 49.2% of narcoleptic individuals were taking a CNS stimulant; at W2, 37% of narcoleptic individuals were taking a CNS stimulant. The use was chronic (i.e., present at W2 and W1) for 52.7% of the W2 subjects. CNS depressants were used by 19.1% at W1 and 17% at W2. Of the W1 subjects, 67.6% still reported using CNS depressants at W2. In terms of antidepressants, 38.6% and 29.6% of subjects reported using these medications at W1 and W2 respectively. Of those taking antidepressants at W2, 58.9% reported chronic use (ie, were also on antidepressants at W1). At least one of the aforementioned medication classes was used by 72% of participants at W1 and 56.1% at W2. Chronicity of nocturnal awakenings (RR: 2.7), the frequency of cataplexy episodes (RR: 2.3) and the chronicity of hypnopompic hallucinations (RR: 2.8) were associated with long-term use of narcolepsy treatment. Conclusion Narcolepsy treatments are mostly taken to long term. Some narcoleptics individuals were able to reduce or stop treatment either because the intensity of symptoms decreased or because they developed coping mechanisms to deal with the symptoms. Support NIH (R01NS044199), the Arrillaga Foundation and Jazz Pharmaceuticals Inc.