International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 148 Review Article: CNS Stimulants Currently Available for Treatments in Patients Suffering with Worldwide Pandemic of Coronavirus Disease Khatija Aslam1, Somia Gul2 Abstract: Outbreak of Coronavirus disease is worldwide pandemic declared by WHO. Patients either suffered from coronavirus infection or not both are physically and mentally disturbed. Patient whom suffered with such pandemic diseases or infections, have a greater risk of mental illnesses such as depression, attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), schizophrenia and mania.CNS stimulants are psychoactive drugs available from resources like from nature (herbal/crude drugs) or from synthetic routes, are used to treat such diseases.In current research, extensive research review is done to find the best CNS stimulants currently available for treatments for such diseases. It is concluded from this research that stimulants that prescribed more frequently are amphetamine, methylphenidate and lisdexamfetamine. Moreover, stimulants that are not prescribed or illicit are like cocaine as such agents caused highly dependency, tolerance and addiction. Keywords : CNS Stimulants, amphetamine, methylphenidate, lisdexamfetamine, Coronavirus. Correspondence to: Somia Gul, Department of Pharmaceutical Chemistry, Faculty of Pharmacy Jinnah University for Women, Karachi, 74600, Pakistan. E-mail: drsomi1983@yahoo.com 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jinnah University for Women, Karachi,Pakistan. 2. Associate Professor, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jinnah University for Women, Karachi,Pakistan. International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 Page : 148-153 DOI: http://dx.doi.org/10.31344/ijhhs.v5i2.251 Introduction Mr. Zia, 50 years old businessman, lived in Karachi. After the death of his wife, his son became addicted to drugs and also suffered from COVID-19, then committed suicide. His daughter noticed that he was suffering from depression. She took appointment and treatment started with counselling by then medicines such as antidepressants, CNS Stimulants and multivitamins to subside the adverse effects. After a while, he recovered from depression and returned back to life. Outbreak of Coronavirus disease is worldwide pandemic declared by WHO. Patients either suffered from coronavirus infection or not both are physically and mentally disturbed.1 According to a recent research published 11 May, 2020, in Pakistan 29 suicide cases were reported.2Patient whom suffered with such pandemic diseases or infections, have a greater risk of mental illnesses such as depression, attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), schizophrenia and mania.3 Moreover, in Pakistan cases were increased day by day (Figure 1 and Figure 2). Figure 1:Total coronavirus cases in Pakistan from February 15–July 08, 2020. (Source: https://www. worldometers.info/coronavirus/country/pakistan/) 149 International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 Figure 2: Outcome of cases (Recovery or Death) in Pakistan from February 15 – July 08. (Source: https://www.worldometers.info/coronavirus/ country/pakistan/) Naturally a type of stimulant presents in our body to maintain and regulates the normal mechanism. Dopamine, serotonin and noradrenaline are the three main chemical agents present in body. Dopamine a neurotransmitter, its high levels may lead to enhance mood and increase motor activity. If too many dopamine presents then its lead to schizophrenia, nervousness and irritability whereas too little levels may lead to paralysis and tremors. According to past researches it is thought that dopamine is a master molecule of addiction.4 5HT Serotonin is a natural mood stabilizer present in central nervous system, digestive track and blood platelets help to reduce anxiety, depression, digestion, sleeping, healing of wound and control nausea.5 Noradrenaline also known as norepinephrine, act as neurotransmitter and hormone. It consists of catecholamine and phenethylamine. Norepinephrine is a mediator to responsible for fight and flight, produced by adrenal glands. It increases heart rate, anxiety, alertness, restlessness and improve memory.6 These chemical substances regulate normal physiological function in body, but sometimes too- much or too-little levels may lead to pathological condition which are prevented or/and treated by medication either natural or synthetic drugs (Table 1 and Table 2).Caution may be taken by the use medication agents such as amphetamine, cocaine, caffeine and methylphenidate caused addiction and dependency in patient if they use long term., usually these medications are used by sport players for anaerobic exercise.7 On the other hand, new generation also suffered from addiction of drugs, such as cocaine, khat, ecstasy, alcohol, smoking, also with substance use disorder (SUB) reported recently.8Variety of drugs are now available to treat or prevent such type of illness and disorders. CNS Stimulants are psychoactive drugs available from resources like from nature (herbal/crude drugs) or from synthetic routes, are used in number of diseases such as attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), depression, narcolepsy, neonatal apnea and sleep disorder.9 Nature has provided countless blessings for human mankind including number of herbs, plants, animals and marine creatures as resources for treatment of different diseases and ailments. Naturally a vast number of CNS Stimulants10-13 are present as herbal or crude form of drug such as caffeine, khat, and cocaineetc. as some most common and advanced herbs are summarized in Table 1. Table 1. Brief Summary of Naturally Available CNS Stimulants. S.NO HERBAL DRUGS DESCRIPTION STRUCTURE 1 Caffeine It had been used ancient as CNS stimulant in China. Pseudoephedrine and ephedrine are the main constituents which increases the heart rate, and stimulates the brain. Ephedra also used in weight loss therapy, but having severe side effects.10,11 2 Ephedra Khat is a Psychoanaleptic found in leaves and plants shoots. Khat contain cathinone as a main constituent responsible for its activity. Cathinone is structurally resembling to amphetamine. It reduces the appetite by increasing the feeling of fullness.11 International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 150 S.NO HERBAL DRUGS DESCRIPTION STRUCTURE 3 Khat Ginkgo is a cognitive enhancer, used for the treatment of lack of attention, vertigo, cerebral vascular diseases and loss of short-term memory.12 4 Ginkgo Centella asiatica is a medicinal herbal plant used to improve cognative functions, having antianxiety properties also improves memory Gotukola used traditionally by chines, its roots and leaves are used to support the healthy tissues of skin and hairs.12 5 Gotukola Panax ginseng dried roots are used in the treatment of Alzheimer’s disease. It reduces fatigue, cholesterol and stress also maintain high blood pressure, heart rate and boost up immune system.12 6 Ginseng Alkaloidal Extract Derived from the coca plant. It produces local anesthetic effect by blocking sodium channel also produce convulgenic effect by blocking NMDA receptors. Cocaine long term use may produce cardiotoxicity.13 7 Cocaine It had been used ancient as CNS stimulant in china. Pseudoephedrine and ephedrine are the main constituents which increases the heart rate, and stimulates the brain. Ephedra also used in weight loss therapy, but having severe side effects.10, 11 Advance research in the field of medicine and new technologies made our lives easier. CNS stimulants are easily available as synthetic form to treat numerous of disease for example; ADHD, OCD, depression, narcolepsy, neonatal apnea and sleep disorder. Caffeine,10 amphetamine, benzphetamine, modafinil, methylphenidate, lisdexamfetamine, dextroamphetamine, metamfetamine, megastrol acetate, pemoline, benzphetamine, minaprine, armodafinil and fencamfamin are currently available for treatment of such types of diseases. They are available in oral, injectable and also in inhaled form (Table 2). Stimulants that prescribed more frequently are amphetamine, lisdexamfetamine, caffeine, methylphenidate and benzphetamine are commercially available.14 Table 2. Brief Summary of Currently Available Synthetic CNS Stimulants. S.no CNS stimulants Description Structure Different renowned brands available worldwide Available dosage form 1 Amph- etamine CNS Stimulant currently available, used to treat ADHD and also used as recreational purpose, highly addicted and also caused weight loss because it suppresses appetite.14 Adzenys XR-ODT, Dyanavel XR, Evekeo. Extended relaease oral disintegrating tablets (Adzenys XR-ODT) Extended relaease oral suspension (Dyanavel XR) 151 International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 S.no CNS stimulants Description Structure Different renowned brands available worldwide Available dosage form 2 Dextroamp- hetamine Sympathomimetic agent used to treat narcolepsy and attention deficit hyperactivity disorder.14 1. Dexedrine 2. Dexedrine spansules 3. Dextrostat 4. Liquadd 5. Procentra 6. Zenzedi Extended release capules (Dexedrine) Oral Solution (Procentra) Immediate release tablets (Zenzedi) 3 Modafinil Used to treat narcolepsy, sleep disorder and promote wakefulness. Sometimes causes allergy or skin rashes.15 Provigil Tablets are available. 4 Methyl- phenidate CNS Stimulant agent used to treat attention deficit disorder ADD and narcolepsy by increasing dopamine and norepinephrine levels in brain. Methylphenidate are controlled release drugs available in capsule, tablets, oral solution and oral suspension form. Methylphenidate long term may cause addiction and dependency in patient.16 Ritalin Aptensio XR Ritalin LA Metadate CD Adhansia XR Jornay PM Methylin Ritalin SR QuilliChew ER Generics Tablet (Ritalin) Extended release capules(Aptensio XR Ritalin LA Metadate CD Adhansia XR) Extended/delayed release capules (Jornay PM) Extended release tablets (Methylin, Ritalin SR, Generics) Extended release chewable tablets (QuilliChew ER) and transdermal patches are also available. 5 Dexmethy- lphenidate It is a nor epinephrine dopamine reuptake inhibitor used in conjugation with other therapies in the treatment of ADHD.16 Focalin, Focalin XR Tablets and extended release capsules are available. 6 Lisdexam- fetamine CNS Stimulant drug used to treat ADHD, severely eating disorder, decrease restlessness in children and also used to improve hyperactivity.17 Vyvanse Available in capsule and chewable tablets. 7 Metam- fetamine Sympathomimetic agents used in the treatment of exogenous obesity and attention deficit hyperactivity disorder.18 Desoxyn Tablets 8 Megastrol acetate Megastrol acetate is a progestin used in the treatment of cachexia, anorexia, weight loss and as an antineoplastic agent.19 Megace, Megace ES. Tablets Oral suspension. 9 Picrotoxin An analeptic class of drug used for relieving respiratory distress. It is also used as an antidote for barbiturate poisoning and GABA receptor antagonist.20 Cocculin, Coques du levant, Cocculine, Cocculus, Fish berry, Oriental berry currently not available International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 152 S.no CNS stimulants Description Structure Different renowned brands available worldwide Available dosage form 10 Doxapram An analeptic class of drug act as short acting respiratory Stimulant available as injectable solution.21 Dopram Injectable solution 11 Armodafinil Used in the treatment of narcolepsy, improve wakefulness, sleep disorders, shift work disorders and sleep apnea available for orally administration22 Nuvigil Available in tablets form. 12 Pemoline CNS Stimulant used in the treatment of narcolepsy and attention deficit hyperactivity disorder but it may cause severe hepatic failure in patient so that not be used as first line agent.23 Cylert Available in tablets and chewable tablets. 13 Benz- phetamine Sympathomimetic short- term agent similar to amphetamine used in the treatment of obesity but not indicating under 17 years of age.24 Didrex Available as tablet form. 14 Fen- camfamin Psychostimulant class of drug used to treat lack of concentration, depressive fatigue and lethargy.25 Reactivan Available in syrup and tablet form. Investigation and research in the field of CNS stimulants reported that, to improve ADHD, JORNAY PM was the only medication dosing in evening to control the symptoms in morning, day and also in evening time (in phase 3 trail). In August 2018, CNS stimulant drug methylphenidate HCL was approved by FDA used for treating ADHD in children 6 years or greater.26 Conclusion: From among the above mention both natural and synthetic central nervous system stimulants,it is found that stimulants that prescribed more frequently are amphetamine, methylphenidate and lisdexamfetamine. These agents are used for the treatment of attention deficit hyperactivity disorder, depression, and narcolepsy and sleep disorder. Methylphenidate (Ritalin) is used as first line agent in attention deficit hyperactivity disorder. Amphetamine (Addrella, Addrella XR) is a most potent CNS stimulant and potential for abused was discovered hundreds of years ago and still it is used for ADHD. Lisdexamfetamine (Vyvanse) is a prodrug of amphetamine used for the treatment of ADHD and narcolepsy. Stimulants that are not prescribed or illicit are like cocaine as such agents caused highly dependency, tolerance and addiction. Conflict of Interest: No conflict of interest exists. Funding: No funding exists. Ethical Approval Issue:Not applicable. Authors’ contribution: Data gathering and idea owner of this study: Somia Gul and Khatija Aslam; Study design: Somia Gul; Data gathering: Khatija Aslam and Somia Gul; Writing and submitting manuscript: Khatija Aslam and Somia Gul; Editing and approval of final draft: Somia Gul. 153 International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 References: 1. World Health Organization. Critical preparedness, readiness and response actions for covid-19: interim guidance, 24 June 2020. No. Who/ covid-19/community actions/2020.4. World Health Organization, 2020. 2. Mamun MA, Ullah I. 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