DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2003/0008919 A1 Roullet Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2003/0008919 A1 Roullet Et Al US 20030008919A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0008919 A1 ROullet et al. (43) Pub. Date: Jan. 9, 2003 (54) USE OF RETINOIDS TO TREAT HIGH Related U.S. Application Data BLOOD PRESSURE AND OTHER CARDOWASCULAR DISEASE (62) Division of application No. 09/325,241, filed on Jun. 3, 1999, now Pat. No. 6,437,003. (76) Inventors: Jean-Baptiste Roullet, Portland, OR (US); David A. McCarron, Portland, Publication Classification OR (US) (51) Int. Cl." ........................ A61K 31/203; A61K 31/07 Correspondence Address: (52) U.S. Cl. ............................................ 514/559; 514/725 MCDONNELL BOEHNEN HULBERT & BERGHOFF (57) ABSTRACT 300 SOUTHWACKER DRIVE SUTE 3200 This invention provides methods of treating a disease in a CHICAGO, IL 60606 (US) mammal where the disease is characterized by a Symptom ameliorated by inhibition of cellular calcium influx. The (21) Appl. No.: 10/223,970 methods involve administering to the mammal an effective amount of a retinoid and a pharmacologically acceptable (22) Filed: Aug. 20, 2002 excipient. Patent Application Publication Jan. 9, 2003 Sheet 1 of 7 US 2003/0008919 A1 Vehicle e Retino O 20 40 SO 80 100 KCI), mM Fig. 1 Patent Application Publication Jan. 9, 2003 Sheet 2 of 7 US 2003/0008919 A1 5 4. KX-O E E 3 O E 2 K 1 occa - 8 ... 7 - 6 - 5 - 4 NE, log(M) Fig. 2 Patent Application Publication Jan. 9, 2003 Sheet 3 of 7 US 2003/0008919 A1 400 300 200 100 Fig. 3 Patent Application Publication Jan. 9, 2003 Sheet 4 of 7 US 2003/0008919 A1 100 80 60 40 20 O 2OO 400 600 (Ca?"), nM Fig. 4 Patent Application Publication Jan. 9, 2003 Sheet 5 of 7 US 2003/0008919 A1 vehicle 100 o - 8O O is Lu £ 60 () N1 C sE 40 O SS 2O O 20 40 60 80 100 KCl), M Fig. 5 Patent Application Publication Jan. 9, 2003 Sheet 6 of 7 US 2003/0008919 A1 NE, logM) Fig. 6 Patent Application Publication Jan. 9, 2003 Sheet 7 of 7 US 2003/0008919 A1 -50 O 50 100 US 2003/OOO8919 A1 Jan. 9, 2003 USE OF RETINOIDS TO TREAT HIGH BLOOD 0006 Thus, in one embodiment, this invention provides PRESSURE AND OTHER CARDIOWASCULAR a method of treating a disease in a mammal where the Said DISEASE disease is characterized by a Symptom ameliorated by inhi bition of cellular calcium influx. The method typically CROSS-REFERENCE TO RELATED involves administering to the mammal an effective amount INVENTIONS of a retinoid and a pharmacologically acceptable excipient. It will be appreciated that while a major application of the 0001. Not Applicable method involves treatment of humans, the methods are not So limited and treatment of virtually any mammal is con STATEMENT AS TO RIGHTS TO INVENTIONS templated. In a particularly preferred embodiment, the mam MADE UNDER FEDERALLY SPONSORED mal is Selected from the group of mammals having a disease RESEARCH AND DEVELOPMENT characterized by one or more Symptoms responsive to 0002) Not Applicable (ameliorated by) inhibition of calcium influx into a cell. 0007. It is primarily contemplated that the methods will BACKGROUND OF THE INVENTION be practiced for the primary purpose of treatment of a condition one or more Symptoms of which are responsive to 0.003 Calcium channel blockers are a relatively recently calcium channel blockage. The methods do not contemplate discovered class of compounds which possess a wide Spec administration of a retinoid for the purpose of diet Supple trum of properties useful in the treatment of cardiovascular, mentation. Thus, the retinoid is not a dietary Supplement. cerebrovascular, intraocular, and other disorders. Calcium The methods may thus additionally involve the step of channel blockers were initially identified as a method for the assaying for retinoid-mediated amelioration of a Symptom of control of hypertension (Fleckenstein et al. (1967) Z. Krei a disease State. Typically the Symptom will be one expected slauforsch, 56: 716), and are routinely used in the control of to be responsive to a calcium channel blocker. Similarly, the hypertension and other disorders. In particular, calcium methods may additionally involve identifying a Subject blockers have shown Some useful therapeutic properties in mammal (e.g., a patient) having a disease State expected to the treatment of classic exertional angina, vasospastic prove responsive to a calcium channel blocker. angina, angina pectoris, acute myocardial infarction, cardiac 0008. The methods can be used to treat a wide variety of arrhythmias, Systemic arterial hypertension, pulmonary arte diseases including, but not limited to essential hypertension, rial hypertension, and cardiomyopathies. In addition, cal hypertension associated with end Stage renal failure, hyper cium channel blockers have shown therapeutic properties in tension associated with pregnancy (preeclampsia), Salt Sen the treatment of various cerebrovascular disorders, including Sitivity hypertension, type II diabetes hypertension, hyper but not limited to migraine headaches, and convulsive tension associated with alcohol abuse, obesity associated epilepsy. hypertension, Systolic hypertension in elderly, asthma, aller 0004 Several structural classes of compounds are known gies, migraine headache, gastrointestinal motility disorders, which exhibit calcium channel blocking utility and have Alzheimer's disease, Senile dementia, angina pectoris, pre been used as therapeutics in a variety of contexts. The three mature labor, cerebrovascular diseases, and convulsive epi major classes include dihydropynidines (e.g., nifedipine, lepsy. The methods, however, are particularly well Suited for felodipine, isradipine, and amlodipine), the benzothiaz treatment of essential hypertension and intra-ocular hyper epines (e.g., diltiazem), and the phenylalkylamines (e.g., tension. Verapamil). Three calcium channel blockers are currently of 0009 Any of a variety of retinoids are suitable. Particu primary clinical Significance in the United States, Verapamil, larly preferred retinoids include retinoic acid and retinol, nifedipine and diltiazem. All three achieve their antihyper with retinol being most preferred. The pharmacologically tensive effect by inhibiting the entry of calcium ions into acceptable excipient is preferably lipid compatible. A most vascular Smooth muscle. The ultimate effect is vasodilation. preferred retinoid inhibits cellular influx of calcium through These calcium blockers are, however, contraindicated in inhibition of Voltage gated channels in particular L-type various circumstances (e.g., where there is impaired left Voltage-gated calcium channels. ventricular function). Thus, there is a need for other calcium blocking agents. 0010. In another embodiment, this invention provides a method of treating a disorder which is responsive to the SUMMARY OF THE INVENTION partial or complete blockade of calcium channels of the central nervous System of a living mammal. Again the 0005 The present identifies previously unknown calcium method involves administering to Such a living mammal in channel blocking properties of retinoids, in particular ret need thereof, a therapeutically effective amount of a retinoid inol, and provides methods of treating pathological condi as described herein. The disorder can include Stroke, anoxia, tions characterized by and ameliorated by inhibition of ischemia, migraine or epilepsy, psychosis, Parkinsonism, cellular calcium influx using retinoids. Retinoids (e.g., Vita depression, or any other convulsive disorder. In Still another min A and analogues) are lipid-Soluble and can therefore embodiment, the method involves treating the degenerative achieve extensive distribution within body tissues. They are changes, connected with Stroke, anoxia, ischemia, migraine, also rapidly absorbed after oral or intravenous administra Parkinsonism, epilepsy or any other convulsive disorder, tion and, because of their affinity for fatty tissues, provide a responsive to the partial or complete blockade of calcium reservoir that maintains elevated retinoid levels for Some channels of the central nervous System of a living animal time after administration. In addition, the physiological body, by administering to a living animal body in need tolerance for many retinoids (e.g., vitamin A) has been thereof a therapeutically-effective amount of a retinoid as repeatedly demonstrated and well characterized. described herein. US 2003/OOO8919 A1 Jan. 9, 2003 0011. In still another embodiment, this invention pro of a drug Sufficient to transiently or permanently reduce vides methods of inhibiting calcium influx into a mamma blood pressure (e.g., diastolic pressure) or to reduce the lian cell. The methods involve contacting the cell with a likelihood of the onset of a stroke. retinoid. The retinoid is present in an amount Sufficient to 0016 A calcium channel is a passive transport mecha inhibit, partially or fully, a calcium channel, more preferably nism by which calcium ions move down their electrochemi a L-type Voltage-gated calcium channel. Virtually any ret cal gradient. In all cells, calcium concentration is low inside inoid is Suitable, however in a preferred embodiment, the the cell (e.g., 107M) and high in the extracellular medium retinoid is retinol or retinoic acid, more preferably retinol. (e.g., 10M) and so a calcium channel allows calcium to go The cell can be virtually any mammalian cell, however into the cell. By contrast, outward calcium transport takes preferred cells include muscle cells, more preferably Smooth place via "a calcium pump, an entirely different mechanism muscle cells, most preferably vascular
Load more

Recommended publications
  • Nootropic Concepts
    Nootropic concepts intelligent ingredient for gut health Nootropics definition Nootropic is a substance that enhances cognition and memory and facilitates learning. Nootropics work in many ways to produce a range of benefits across memory, focus, attention, motivation, relaxation, mood, alertness, stress resistance. Bluenesse® Bluenesse® – an innovative, exclusive lemon balm extract, Melissa officinalis (L.) – supports your mental health. It has an immediate effect on focus, concentration, and memory. Furthermore, it supports a calm and good mood and helps to balance the stress hormone cortisol. Bluenesse® - Nootropics concepts Nootropic benefits of Bluenesse® and the underlying mode of action: Bluenesse® - Nootropics concepts – detailed information: Several, double blind, randomized, placebo-controlled, crossover human study results have shown that Bluenesse® supports nootropic effects on demand. Below, the investigated parameter and mode of action is explained per each nootropic application. Vital Solutions GmbH, Hausingerstrasse 6, D-40764 Langenfeld, +49 (0) 2173 109 82 02 [email protected] www.vitalsolutions.biz . Nootropic concepts Cognitive performance support and enhancing learning & memory: Bluenesse® significantly improves cognitive performance, particularly alertness, working memory and mathematic processing by improving the efficiency of neuronal communication. It activates Muscarinic receptors, which are responsible for the efficient flow of information between neurological cells, so-called “oscillation”, leading to
    [Show full text]
  • Nootropics for Healthy Individuals
    Trinity College Trinity College Digital Repository Trinity Publications (Newspapers, Yearbooks, The First-Year Papers (2010 - present) Catalogs, etc.) 2015 Nootropics for Healthy Individuals Jin Pyo Jeon Trinity College, Hartford Connecticut, [email protected] Follow this and additional works at: https://digitalrepository.trincoll.edu/fypapers Part of the Chemicals and Drugs Commons Recommended Citation Jeon, Jin Pyo, "Nootropics for Healthy Individuals". The First-Year Papers (2010 - present) (2015). Trinity College Digital Repository, Hartford, CT. https://digitalrepository.trincoll.edu/fypapers/61 Nootropics for Healthy Individuals Jin Pyo Jeon With recent advances in fields like biotechnology and genetic engineering, the concern for a just and equal distribution of human enhancement technologies undoubtedly became one of the most significant ethical dilemmas of the 21st century. And with the sudden rise of cognitive enhancement drug (otherwise called as nootropics) use in society, the need for developing policies to address these dilemmas have now become an urgent issue that the scientific and political community must confront. Once only used by the few with special needs or neurological disorders, nootropics are now being utilized by a significant part of the population for cognitive enhancement, inciting a debate of the regulation and legalization of nootropics. Nonetheless, given the currently known benefits and risks of nootropics, the mechanisms through which nootropics function, and the ineffectiveness of policy restrictions, it would be more pragmatic to inform and allow for the non-prescription uses for some nootropics rather than to restrict its use. Benefits, Risks, and Viability of the Use of Nootropics Among many other nootropics, two drugs have become the de facto nootropics for many healthy individuals: modafinil (commercially known as Provigil) and methylphenidate (commercially known as Ritalin).
    [Show full text]
  • Neuroenhancement in Healthy Adults, Part I: Pharmaceutical
    l Rese ca arc ni h li & C f B o i o l e Journal of a t h n Fond et al., J Clinic Res Bioeth 2015, 6:2 r i c u s o J DOI: 10.4172/2155-9627.1000213 ISSN: 2155-9627 Clinical Research & Bioethics Review Article Open Access Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review Fond G1,2*, Micoulaud-Franchi JA3, Macgregor A2, Richieri R3,4, Miot S5,6, Lopez R2, Abbar M7, Lancon C3 and Repantis D8 1Université Paris Est-Créteil, Psychiatry and Addiction Pole University Hospitals Henri Mondor, Inserm U955, Eq 15 Psychiatric Genetics, DHU Pe-psy, FondaMental Foundation, Scientific Cooperation Foundation Mental Health, National Network of Schizophrenia Expert Centers, F-94000, France 2Inserm 1061, University Psychiatry Service, University of Montpellier 1, CHU Montpellier F-34000, France 3POLE Academic Psychiatry, CHU Sainte-Marguerite, F-13274 Marseille, Cedex 09, France 4 Public Health Laboratory, Faculty of Medicine, EA 3279, F-13385 Marseille, Cedex 05, France 5Inserm U1061, Idiopathic Hypersomnia Narcolepsy National Reference Centre, Unit of sleep disorders, University of Montpellier 1, CHU Montpellier F-34000, Paris, France 6Inserm U952, CNRS UMR 7224, Pierre and Marie Curie University, F-75000, Paris, France 7CHU Carémeau, University of Nîmes, Nîmes, F-31000, France 8Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany *Corresponding author: Dr. Guillaume Fond, Pole de Psychiatrie, Hôpital A. Chenevier, 40 rue de Mesly, Créteil F-94010, France, Tel: (33)178682372; Fax: (33)178682381; E-mail: [email protected] Received date: January 06, 2015, Accepted date: February 23, 2015, Published date: February 28, 2015 Copyright: © 2015 Fond G, et al.
    [Show full text]
  • Nootropic and Anti-Alzheimer's Actions of Medicinal Plants
    Molecular Neurobiology (2019) 56:4925–4944 https://doi.org/10.1007/s12035-018-1420-2 Nootropic and Anti-Alzheimer’s Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer’s Neuropathology Md. Sahab Uddin1 & Abdullah Al Mamun1 & Md. Tanvir Kabir 2 & Md. Jakaria3 & Bijo Mathew4 & George E. Barreto5,6 & Ghulam Md Ashraf7 Received: 5 September 2018 /Accepted: 29 October 2018 /Published online: 9 November 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Medicinal plants are the backbone of modern medicine. In recent times, there is a great urge to discover nootropic medicinal plants to reverse cognitive dysfunction owing to their less adverse effects. Alzheimer’s disease (AD) is an age-related neurode- generative disorder characterized by the inevitable loss of cognitive function, memory and language impairment, and behavioral disturbances, which turn into gradually more severe. Alzheimer’s has no current cure, but symptomatic treatments are available and research continues. The number of patients suffering from AD continues to rise and today, there is a worldwide effort under study to find better ways to alleviate Alzheimer’s pathogenesis. In this review, the nootropic and anti-Alzheimer’spotentialsof6 medicinal plants (i.e., Centella asiatica, Clitoria ternatea, Crocus sativus, Terminalia chebula, Withania somnifera,and Asparagus racemosus) were explored through literature review. This appraisal focused on available information about neuro- protective and anti-Alzheimer’s use of these plants and their respective bioactive compounds/metabolites and associated effects in animal models and consequences of its use in human as well as proposed molecular mechanisms. This review progresses our existing knowledge to reveal the promising linkage of traditional medicine to halt AD pathogenesis.
    [Show full text]
  • Drugs Influencing Cognitive Function
    Indian J Physiol Phannacol 1994; 38(4) : 241-251 RE\llEW ARTICLE DRUGS INFLUENCING COGNITIVE FUNCTION ALICE KURUYILLA* AND YASUNDARA DEYI Department ofPharmacology. Christian Medical College. Vellore - 632 002 DRUGS INFLUENCING COGNITIVE FUNCTION cerebrovascular disorders with dementias and reversible dementias. Drugs can inOuence cognitive function in several different ways. The cognitrve enhancers or nootropics Primary degenerative disorders include the have become a major issue in drug development during subgroups senile dementia of the Alzheimer's type the last decade. Nootropics arc defined as drugs that (SDAT), Alzheimer's disease, Picks disease and generally increase neuron metabolic activity, improve Huntington's chorea (4). Alzheimer's disease usually cognitive and ,'igilance level and are said to have occurs in individuals past 70 years old and appears to antidemcntia effect (I). These drugs are essential for be in part genetically determin'd (5). the treatment of geriatric disorders like Alzheimer's which have become one of the major problems socially Pathophysiology oj Alzheimer's disease : and medically. Considerable evidence has been gathered Extensive research in the recent years has made major in the last decade to support the observation that advances in understanding the pathogenesis of children with epilepsy have morc learning difficulties Alzheimer's disease (6). The hallmark lesions of than age matched controls (2, 3). Anti-epileptic drugs Alzheimer's disease are neuritic plaques and are useful in controlling the frequency and duration of neurofibrillary tangles. Two amyloid proteins seizures. These drugs can also be the source of side accumulate in Alzheimer's disease, these arc beta effects including cognitive impairment.
    [Show full text]
  • For Peer Review Only
    BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-012177 on 30 November 2016. Downloaded from Commonly prescribed drugs associated with cognition: a cross-sectional study in UK Biobank ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2016-012177 Article Type: Research Date Submitted by the Author: 06-Apr-2016 Complete List of Authors: Nevado-Holgado, Alejo; University of Oxford, Psychiatry Kim, Chi-Hun; University of Oxford, Psychiatry Winchester, Laura; University of Oxford, Psychiatry Gallacher, John; University of Oxford, Psychiatry Lovestone, Simon; University of Oxford, Psychiatry <b>Primary Subject Public health Heading</b>: Secondary Subject Heading: Mental health, Pharmacology and therapeutics, Neurology Keywords: PUBLIC HEALTH, MENTAL HEALTH, Cognition, UK biobank http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected copyright. For peer review only − http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 16 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-012177 on 30 November 2016. Downloaded from 1 2 3 Commonly prescribed drugs associate with cognition: a cross-sectional study 4 in UK Biobank 5 6 7 8 Authors 9 10 Alejo J Nevado-Holgado*, Chi-Hun Kim*, Laura Winchester, John Gallacher, Simon Lovestone 11 12 13 14 15 Address For peer review only 16 17 Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK 18 19 20 21 22 23 Authors’ names and positions 24 25 Alejo J Nevado-Holgado*: Postdoctoral researcher 26 27 Chi-Hun Kim*: Postdoctoral researcher 28 29 Laura Winchester: Postdoctoral researcher 30 31 John Gallacher: Professor 32 33 Simon Lovestone: Professor 34 http://bmjopen.bmj.com/ 35 *These authors contributed equally to this work.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2007/0155676 A1 Burnett Et Al
    US 20070 155676A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0155676 A1 Burnett et al. (43) Pub. Date: Jul. 5, 2007 (54) SUBSTITUTED AZETIONONE (60) Provisional application No. 60/452,725, filed on Mar. COMPOUNDS, PROCESSES FOR 7, 2003. PREPARING THE SAME, FORMULATIONS AND USES THEREOF Publication Classification (75) Inventors: Duane A. Burnett, Bernardsville, NJ (51) Int. Cl. (US); John W. Clader, Cranford, NJ A61K 3 1/7052 (2006.01) (US) A6II 3 L/506 (2006.01) A61K 31/4709 (2006.01) Correspondence Address: A61K 31/4025 (2006.01) SCHERING-PLOUGH CORPORATION A61K 31/4439 (2006.01) PATENT DEPARTMENT (K-6-1, 1990) A 6LX 3L/397 (2006.01) 2000 GALLOPNG HILL ROAD C07D 405/14 (2006.01) KENILWORTH, NJ 07033-0530 (US) C07D 405/02 (2006.01) (52) U.S. Cl. ..................... 514/23: 514/210.02:536/17.3; (73) Assignee: Schering Corporation, Kenilworth, NJ 54O72OO (21) Appl. No.: 11/708,449 (57) ABSTRACT Filed: Feb. 20, 2007 The present invention provides substituted azetidinone com (22) pounds, formulations and processes for preparing the same Related U.S. Application Data which can be useful for treating vascular conditions such as atherosclerosis or hypercholesterolemia, diabetes, obesity, (62) Division of application No. 10/792.346, filed on Mar. stroke, demyelination and lowering plasma levels of sterols 3, 2004, now Pat. No. 7,208,486. and/or stanols in a subject. US 2007/O 155676 A1 Jul. 5, 2007 SUBSTITUTED AZETIDINONE COMPOUNDS, 0006 U.S. Pat. Nos. 5,846,966 and 5,661,145, respec PROCESSES FOR PREPARING THE SAME, tively, disclose treatments for inhibiting atherosclerosis and FORMULATIONS AND USES THEREOF reducing plasma cholesterol levels using Such hydroxy Substituted aZetidinone compounds or Substituted B-lactam CROSS-REFERENCE TO RELATED compounds in combination with HMG CoA reductase APPLICATION inhibitor compounds, which act by blocking hydroxymeth 0001.
    [Show full text]
  • The Use and Impact of Cognitive Enhancers Among University Students: a Systematic Review
    brain sciences Systematic Review The Use and Impact of Cognitive Enhancers among University Students: A Systematic Review Safia Sharif 1 , Amira Guirguis 1,2,* , Suzanne Fergus 1,* and Fabrizio Schifano 1 1 Psychopharmacology, Substance Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK; [email protected] (S.S.); [email protected] (F.S.) 2 Institute of Life Sciences 2, Swansea University, Swansea SA2 8PP, Wales, UK * Correspondence: [email protected] (A.G.); [email protected] (S.F.) Abstract: Introduction: Cognitive enhancers (CEs), also known as “smart drugs”, “study aids” or “nootropics” are a cause of concern. Recent research studies investigated the use of CEs being taken as study aids by university students. This manuscript provides an overview of popular CEs, focusing on a range of drugs/substances (e.g., prescription CEs including amphetamine salt mixtures, methylphenidate, modafinil and piracetam; and non-prescription CEs including caffeine, cobalamin (vitamin B12), guarana, pyridoxine (vitamin B6) and vinpocetine) that have emerged as being misused. The diverted non-prescription use of these molecules and the related potential for dependence and/or addiction is being reported. It has been demonstrated that healthy students (i.e., those without any diagnosed mental disorders) are increasingly using drugs such as methylphenidate, a mixture of dextroamphetamine/amphetamine, and modafinil, for the purpose of increasing their alertness, concentration or memory. Aim: To investigate the level of knowledge, perception and impact of the use of a range of CEs within Higher Education Institutions.
    [Show full text]
  • Practitioner Dietary Supplement Reference Guide
    Practitioner Dietary Supplement Reference Guide dotFIT™ ThermAccelTM Goal To accelerate or continue desired weight loss, especially when diet and exercise may be maximized based on acceptable lifestyle parameters, by supplying effectively timed doses of bioactive ingredients that have separately demonstrated favorable effects through unique targets on human body fat metabolism leading to enhanced body fat/weight loss when compared to a non-supplemented state. Daily simultaneous ingestion of these combined actives may contribute additive effects since the individual mechanisms of action related to fat oxidation, energy expenditure and appetite are distinctly unique. The formula’s primary goal is to increase total daily energy expenditure/calorie burn (TDEE) by increasing resting energy expenditure (REE) and overall metabolism including daily activities. ThermAccel’s (TA) natural thermogenic blend is uniquely formulated to deliver a “better stimulant effect” when compared to currently available popular energy formulas that often lead to "burnout" and related stress, including "end of day fatigue." ThermAccel is designed to produce balanced and enhanced energy levels that may also help users increase voluntary daily activities. Through TA’s thermogenic effect (boosting metabolism by wasting calories as heat), favorable fat oxidation properties and smoother daily energy boost, users may be able to avoid or overcome natural plateaus during weight reduction without having to continually "add more work.” TA’s secondary endpoints are to increase fat oxidation/burning (energy/nutrient partitioning) and decrease appetite beyond TA’s caffeine stimulant blend’s normal effects on these targets, by incorporating two other groups of natural ingredients, Caralluma fimbriata and Sinetrol (the polyphenols naringin and neohesperidin), which work through respectively different body fat regulation pathways than the thermogenic blend.
    [Show full text]
  • Cognitive Enhancers
    Cognitive enhancers Memory enhancers are often referred to as "smart drugs", "study drugs",[1] "smart nutrients", "cognitive enhancers", "brain enhancers" or in the scientific literature as nootropics.[2] They are drugs that are purported to improve human cognitive abilities.[3][4] The term covers a broad range of substances including drugs, nutrients and herbs with purported cognitive enhancing effects. The word nootropic was coined in 1964 by Dr. Corneliu E. Giurgea, derived from the Greek words noos, or "mind," and tropein meaning "to bend/turn". Typically, nootropics are thought to work by altering the availability of the brain's supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen supply, or by stimulating nerve growth. However the efficacy of nootropic substances in most cases has not been conclusively determined. This is complicated by the difficulty of defining and quantifying cognition and intelligence. Contents 1 Availability 2 Examples 2.1 Stimulants 2.2 Replenishing and increasing neurotransmitters 2.2.1 Cholinergics 2.2.1.1 Piracetam 2.2.1.2 Aniracetam 2.2.1.3 Other cholinergics 2.2.1.4 Acetylcholinesterase inhibitors 2.2.2 Dopaminergics 2.2.3 Serotonergics 2.3 Anti-depression, adaptogenic (antistress), and mood stabilization 2.4 Brain function and improved oxygen supply 2.5 Purported memory enhancement and learning improvement 2.6 Nerve growth stimulation and brain cell protection 2.7 Recreational drugs with purported nootropic effects 2.8 Dietary nootropics 2.9 Other nootropics 2.9.1 Contentious or possibly unsafe nootropics 3 See also 3.1 Brain and neurology 3.2 Thought and thinking (what nootropics are used for) 3.3 Health 4 References 5 External links Availability Currently there are several drugs on the market that improve memory, concentration, planning and reduce impulsive behavior.
    [Show full text]
  • Impact of a Purported Nootropic Supplementation on Measures of Mood, Stress, and Marksmanship Performance in U.S
    Barringer et al. Journal of the International Society of Sports Nutrition (2018) 15:26 https://doi.org/10.1186/s12970-018-0229-8 RESEARCHARTICLE Open Access Impact of a purported nootropic supplementation on measures of mood, stress, and marksmanship performance in U.S. active duty soldiers Nicholas Barringer1* , Aaron Crombie2 and Russ Kotwal3 Abstract Background: The purpose of this study was to determine the impact of a commercially available purported nootropic supplement on mood, stress, and rifle marksmanship accuracy and engagement time via an Engagement Skills Trainer. Methods: In this double-blind, placebo-controlled trial, 43 U.S. active duty Soldiers participating in a professional military course were assigned to treatment (n = 20; 16 males and 4 females) or placebo (n = 23; 15 males and 8 females) based on initial marksmanship score. The study period was 31 days (testing performed on days 1 and 31, supplementation days 2 through 30). Participants were instructed to consume 2 pills at breakfast and 1 pill at dinner for a total of 3 pills per day (1925 mg) of either the Alpha Brain® nootropic supplement or a placebo. Height, weight, cortisol (in a hair sample), body composition using multi-frequency tetrapolar bioelectrical impedance (InBody 720), and marksmanship (Engagement Skills Trainer 2000). Marksmanship was assessed in the prone position with zeroed M-4 rifles with a twenty target protocol with targets presenting and remaining for 3 s at set intervals. Participants’ performance were assessed with hits versus misses, distance of hit from target center mass (DCM), and target engagement speed. Statistical analysis via SPSS Statistics 21 (IBM) was conducted using a repeated measures ANOVA with significance set at P < 0.5.
    [Show full text]
  • World of Cognitive Enhancers
    ORIGINAL RESEARCH published: 11 September 2020 doi: 10.3389/fpsyt.2020.546796 The Psychonauts’ World of Cognitive Enhancers Flavia Napoletano 1,2, Fabrizio Schifano 2*, John Martin Corkery 2, Amira Guirguis 2,3, Davide Arillotta 2,4, Caroline Zangani 2,5 and Alessandro Vento 6,7,8 1 Department of Mental Health, Homerton University Hospital, East London Foundation Trust, London, United Kingdom, 2 Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom, 3 Swansea University Medical School, Institute of Life Sciences 2, Swansea University, Swansea, United Kingdom, 4 Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy, 5 Department of Health Sciences, University of Milan, Milan, Italy, 6 Department of Mental Health, Addictions’ Observatory (ODDPSS), Rome, Italy, 7 Department of Mental Health, Guglielmo Marconi” University, Rome, Italy, 8 Department of Mental Health, ASL Roma 2, Rome, Italy Background: There is growing availability of novel psychoactive substances (NPS), including cognitive enhancers (CEs) which can be used in the treatment of certain mental health disorders. While treating cognitive deficit symptoms in neuropsychiatric or neurodegenerative disorders using CEs might have significant benefits for patients, the increasing recreational use of these substances by healthy individuals raises many clinical, medico-legal, and ethical issues. Moreover, it has become very challenging for clinicians to Edited by: keep up-to-date with CEs currently available as comprehensive official lists do not exist. Simona Pichini, Methods: Using a web crawler (NPSfinder®), the present study aimed at assessing National Institute of Health (ISS), Italy Reviewed by: psychonaut fora/platforms to better understand the online situation regarding CEs.
    [Show full text]