The Importance of Serotonergic and Adrenergic Receptors for the Induction and Expression of One-Trial Cocaine-Induced Behavioral Sensitization" (2016)
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Adrenergic Antagonist
PHARMACOLOGY Adrenergic antagonist OBJECTIVES: • Describe the different classifications for drugs that can block sympathetic nervous system. •Describe the kinetics, dynamics, uses and side effects of alpha adrenergic drugs. • Identify Difference between selective and non selective alpha blockers. • Know the difference between tamsulosin and other selective alpha receptor blockers. •Identify the different classifications for beta receptors blockers. •Describe the kinetics, dynamics, uses and side effects of beta adrenergic drugs. •Know the preferable drug for diseases as hypertension, glaucoma, arrythmia, myocardial infarction, anxiety, migraine and ect…. • Important. • Extra notes It’s a recall, if you know it you can skip it! Adrenergic receptors Adrenergic receptors Dopaminergic adrenoceptors adrenoceptors α− β− receptors β3 α1 α2 β1 β2 e.g. D1 α1 β2 β1 β3 Post-synaptic excitatory in function (cause inhibitory in function excitatory in In adipose contraction) except in GIT. (cause relaxation) function, present tissue mainly in heart Present mainly in smooth muscles. Contraction of pregnant Relaxation of the uterus ↑ heart rate: ↑ lipolysis uterus. (Delay premature labor) + chronotropic ↑ free fatty effect, Vasoconstriction of skin & Relaxation of skeletal & acids. Tachycardia peripheral blood vessels coronary blood vessels →increased peripheral (vasodilatation) ↑ force of → resistance hypertension. contraction : Relaxation of GIT muscles & urinary bladder’s muscles. + inotropic effect Contraction of GIT sphincter (constipation) & urinary -
Guanfacine Extended Release for ADHD
Out of the Pipeline p Guanfacine extended release for ADHD Floyd R. Sallee, MD, PhD uanfacine extended release (GXR)— Table 1 α Once-daily a selective -2 adrenergic agonist Guanfacine extended release: GFDA-approved for the treatment formulation may of attention-defi cit/hyperactivity disor- Fast facts improve adherence der (ADHD)—has demonstrated effi cacy Brand name: Intuniv and control for inattentive and hyperactive/impulsive Indication: Attention-defi cit/hyperactivity symptoms across disorder symptom domains in 2 large trials lasting® Dowden Health Media a full day 8 and 9 weeks.1,2 GXR’s once-daily formu- Approval date: September 3, 2009 lation may increase adherence and deliver Availability date: November 2009 consistent control of symptomsCopyright across a For personalManufacturer: use Shire only full day (Table 1). Dosing forms: 1-mg, 2-mg, 3-mg, and 4-mg extended-release tablets Recommended dosage: 0.05 to 0.12 mg/kg Clinical implications once daily GXR exhibits enhancement of noradren- ergic pathways through selective direct receptor action in the prefrontal cortex.3 brain believed to play a major role in at- This mechanism of action is different from tentional and organizational functions that that of other FDA-approved ADHD medi- preclinical research has linked to ADHD.3 cations. GXR can be used alone or in com- The postsynaptic α-2A receptor is bination with stimulants or atomoxetine thought to play a central role in the opti- for treating complex ADHD, such as cases mal functioning of the PFC as illustrated accompanied by oppositional features and by the “inverted U hypothesis of PFC ac- emotional dysregulation or characterized tivation.”4 In this model, cyclic adenos- by partial stimulant response. -
Principle of Pharmacodynamics
Principle of pharmacodynamics Dr. M. Emamghoreishi Full Professor Department of Pharmacology Medical School Shiraz University of Medical Sciences Email:[email protected] Reference: Basic & Clinical Pharmacology: Bertrum G. Katzung and Anthony J. Treveror, 13th edition, 2015, chapter 20, p. 336-351 Learning Objectives: At the end of sessions, students should be able to: 1. Define pharmacology and explain its importance for a clinician. 2. Define ―drug receptor‖. 3. Explain the nature of drug receptors. 4. Describe other sites of drug actions. 5. Explain the drug-receptor interaction. 6. Define the terms ―affinity‖, ―intrinsic activity‖ and ―Kd‖. 7. Explain the terms ―agonist‖ and ―antagonist‖ and their different types. 8. Explain chemical and physiological antagonists. 9. Explain the differences in drug responsiveness. 10. Explain tolerance, tachyphylaxis, and overshoot. 11. Define different dose-response curves. 12. Explain the information that can be obtained from a graded dose-response curve. 13. Describe the potency and efficacy of drugs. 14. Explain shift of dose-response curves in the presence of competitive and irreversible antagonists and its importance in clinical application of antagonists. 15. Explain the information that can be obtained from a quantal dose-response curve. 16. Define the terms ED50, TD50, LD50, therapeutic index and certain safety factor. What is Pharmacology?It is defined as the study of drugs (substances used to prevent, diagnose, and treat disease). Pharmacology is the science that deals with the interactions betweena drug and the bodyor living systems. The interactions between a drug and the body are conveniently divided into two classes. The actions of the drug on the body are termed pharmacodynamicprocesses.These properties determine the group in which the drug is classified, and they play the major role in deciding whether that group is appropriate therapy for a particular symptom or disease. -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors. -
The Adrenergic Control of Lower Esophageal Sphincter Function: an EXPERIMENTAL MODEL of DENERVATION SUPERSENSITIVITY
The Adrenergic Control of Lower Esophageal Sphincter Function: AN EXPERIMENTAL MODEL OF DENERVATION SUPERSENSITIVITY Anthony J. DiMarino, Sidney Cohen J Clin Invest. 1973;52(9):2264-2271. https://doi.org/10.1172/JCI107413. To evaluate the adrenergic regulation of lower esophageal sphincter (LES) function, LES pressure, LES relaxation during swallowing, and blood pressure were measured in the anesthetized opossum, Didelphis virginiana, during intravenous administration of alpha and beta adrenergic agonists and antagonists. Studies were done in controls and animals adrenergically denervated with 6-hydroxydopamine. Alpha adrenergic agonists (norepinephrine, phenylephrine) increased LES pressure and blood pressure, whereas a beta adrenergic agonist (isoproterenol) decreased both pressures. Alpha adrenergic antagonism (phentolamine) reduced basal LES pressure by 38.3±3.8% (mean ±SEM) (P < 0.001). Beta adrenergic antagonism (propranolol) had no significant effect on either basal LES pressure or percent of LES relaxation with swallowing. After adrenergic denervation with 6-hydroxydopamine, basal LES pressure was reduced by 22.5±5.3% (P < 0.025) but LES relaxation during swallowing was unaltered. In denervated animals, both LES pressure and blood pressure dose response curves showed characteristics of denervation supersensitivity to alpha but not to beta adrenergic agonists. These studies suggest: (a) a significant portion of basal LES pressure is dependent upon alpha adrenergic stimulation; (b) LES relaxation during swallowing is not an adrenergically mediated response; c( ) the LES pressure response to alpha adrenergic agonists after 6-hydroxydopamine may serve as a model of denervation supersensitivity in the gastrointestinal tract. Find the latest version: https://jci.me/107413/pdf The Adrenergic Control of Lower Esophageal Sphincter Function AN EXPERIMENTAL MODEL OF DENERVATION SUPERSENSITIVITY ANTHoNY J. -
A1-Blocker Therapy in the Nineties: Focus on the Disease
Prostate Cancer and Prostatic Diseases (1999) 2 Suppl 4, S9±S15 ß 1999 Stockton Press All rights reserved 1365±7852/99 $15.00 http://www.stockton-press.co.uk/pcan a1-Blocker therapy in the nineties: focus on the disease KHoÈfner1* 1Department of Urology, Hannover Medical School, Hannover, Germany Therapy for benign prostatic hyperplasia has evolved rapidly over the last decade, with the introduction in the early 1990s of new agents such as a1-blockers and 5a-reductase inhibitors. The major advantage of a1-blockers over 5a- reductase inhibitors is their rapid onset of action. Maximum ¯ow rate is improved after ®rst administration and optimal symptom relief is usually reached within 2 ± 3 months. In addition, a1-blockers are effective regardless of prostate size and they provide a similar degree of symptom relief in patients with or without bladder outlet obstruction. The main adverse events with the a1- blockers relate to their effects on the cardiovascular system (postural hypoten- sion) and central penetration (asthenia, somnolence). Newer uroselective a1- blockers, such as alfuzosin and tamsulosin, have a better safety pro®le and, as such, do not require initial dose titration. Alfuzosin has also been shown in a six- month study to signi®cantly reduce both residual urine and the incidence of acute urinary retention (AUR) compared with placebo. In addition, alfuzosin is effective in improving the success rate of a trial without catheter in patients with AUR. Keywords: benign prostatic hyperplasia; prostate; a1-blockers; 5a-reductase inhibitors; acute urinary retention; LUTS Management of BPH adrenoceptors. Medical management of BPH suddenly exploded at the beginning of the 1990s with the introduc- Therapy for benign prostatic hyperplasia (BPH) has tion of selective a1-blockers and 5a-reductase inhibitors. -
F3-Adrenergic Antagonist (Receptors/Cyclic AMP/Aminobenzylpropranolol/Iodohydroxybenzylpindolol/Isoproterenol) WESLEY L
Proc. Natl. Acad. Sci. USA Vol. 76, No. 12, pp. 6401-6405, December 1979 Cell Biology Quantitative relationship between 3-adrenergic receptor number and physiologic responses as studied with a long-lasting f3-adrenergic antagonist (receptors/cyclic AMP/aminobenzylpropranolol/iodohydroxybenzylpindolol/isoproterenol) WESLEY L. TERASAKI, JOEL LINDEN, AND GARY BROOKER* Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908 Communicated by Paul Greengard, August 20, 1979 ABSTRACT The aminobenzyl analog of propranolol, atrium when f3-adrenergic receptor number is selectively de- 1- (p-amino-a,a-dimethylphenethylamino)-3(1-naphthoxy)2- creased. To investigate this problem, a new propanol, was synthesized and found tobe a potent B-adrenergic f3-adrenergic blocking agent. The fl-adrenergic receptors of cultured rat C6 blocking agent, 1-(p-amino-a,a-dimethylphenethylamino- glioma cells (2B clone) as assessed by [' 51]iodohydroxybenzyl- 3-(1-naphthoxy)-2-propanol (aminobenzylpropranolol), was pindolol binding were decreased 50 and >95% afterpretreat- synthesized. It was found to be a selective agent for the elimi- ment with 8 nM and 1 ,M aminobenzylpropranolol, respec- nation of cellular /3-adrenergic receptors. tively. Unlike propranolol, aminobenzylpropranolol displayed a prolonged blockade of receptors that was maintained during several hours of washing. [121s]Iodohydroxybenzylpindolol MATERIALS AND METHODS saturation binding experiments in cells exposed to aminoben- Tissue Culture. C6 rat glioma cells, 2B subclone (7), were zylpropranolol and subsequently washed indicated that the compound effectively diminished receptor number with no grown in monolayer cultures as described (1) in 16-mm plastic change in the affinity of the remaining receptors for iodohy- cluster dishes. In all experiments, the cells were changed from droxybenzylpindolol. -
Anew Drug Design Strategy in the Liht of Molecular Hybridization Concept
www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 “Drug Design strategy and chemical process maximization in the light of Molecular Hybridization Concept.” Subhasis Basu, Ph D Registration No: VB 1198 of 2018-2019. Department Of Chemistry, Visva-Bharati University A Draft Thesis is submitted for the partial fulfilment of PhD in Chemistry Thesis/Degree proceeding. DECLARATION I Certify that a. The Work contained in this thesis is original and has been done by me under the guidance of my supervisor. b. The work has not been submitted to any other Institute for any degree or diploma. c. I have followed the guidelines provided by the Institute in preparing the thesis. d. I have conformed to the norms and guidelines given in the Ethical Code of Conduct of the Institute. e. Whenever I have used materials (data, theoretical analysis, figures and text) from other sources, I have given due credit to them by citing them in the text of the thesis and giving their details in the references. Further, I have taken permission from the copyright owners of the sources, whenever necessary. IJCRT2012039 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 284 www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 f. Whenever I have quoted written materials from other sources I have put them under quotation marks and given due credit to the sources by citing them and giving required details in the references. (Subhasis Basu) ACKNOWLEDGEMENT This preface is to extend an appreciation to all those individuals who with their generous co- operation guided us in every aspect to make this design and drawing successful. -
Mutation of the 2A-Adrenoceptor Impairs Working Memory Performance and Annuls Cognitive Enhancement by Guanfacine
The Journal of Neuroscience, October 1, 2002, 22(19):8771–8777 ␣ Mutation of the 2A-Adrenoceptor Impairs Working Memory Performance and Annuls Cognitive Enhancement by Guanfacine Jenna S. Franowicz,1 Lynn E. Kessler,1 Catherine M. Dailey Borja,1 Brian K. Kobilka,2 Lee E. Limbird,3 and Amy F. T. Arnsten1 1Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, 2Howard Hughes Medical Institute and Departments of Medicine and Molecular and Cellular Physiology, Stanford University, Palo Alto, California 94305, and 3Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 Norepinephrine strengthens the working memory, behavioral cortical damage or a spatial discrimination control task with inhibition, and attentional functions of the prefrontal cortex similar motor and motivational demands but no dependence on ␣ ␣ through actions at postsynaptic 2-adrenoceptors ( 2-AR). The prefrontal cortex. The effects of guanfacine on performance of ␣ 2-AR agonist guanfacine enhances prefrontal cortical func- the delayed alternation task were assessed in additional groups ␣ tions in rats, monkeys, and human beings and ameliorates of wild-type versus 2A-AR mutant mice. We observed that ␣ prefrontal cortical deficits in patients with attention deficit hy- functional loss of the 2A-AR subtype, unlike knock-out of the ␣ peractivity disorder. The present study examined the subtype of 2C-AR subtype, weakened performance of the prefrontal cor- ␣ 2-AR underlying these beneficial effects. Because there are no tical task without affecting learning and resulted in loss of the ␣ ␣ ␣ selective 2A-AR, 2B-AR, or 2C-AR agonists or antagonists, beneficial response to guanfacine. These data demonstrate the ␣ genetically altered mice were used to identify the molecular importance of 2A-AR subtype stimulation for the cognitive target of the action of guanfacine. -
International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification
0031-6997/03/5504-597–606$7.00 PHARMACOLOGICAL REVIEWS Vol. 55, No. 4 Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics 30404/1114803 Pharmacol Rev 55:597–606, 2003 Printed in U.S.A International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology RICHARD R. NEUBIG, MICHAEL SPEDDING, TERRY KENAKIN, AND ARTHUR CHRISTOPOULOS Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (R.R.N.); Institute de Recherches Internationales Servier, Neuilly sur Seine, France (M.S.); Systems Research, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina (T.K.); and Department of Pharmacology, University of Melbourne, Parkville, Australia (A.C.) Abstract ............................................................................... 597 I. Introduction............................................................................ 597 II. Working definition of a receptor .......................................................... 598 III. Use of drugs in definition of receptors or of signaling pathways ............................. 598 A. The expression of amount of drug: concentration and dose ............................... 598 1. Concentration..................................................................... 598 2. Dose. ............................................................................ 598 B. General terms used to describe drug action ........................................... -
Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders
Neuropsychopharmacology (2003) 28, 402–412 & 2003 Nature Publishing Group All rights reserved 0893-133X/03 $25.00 www.neuropsychopharmacology.org Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders ,1 2 3 2 Gerard J Marek* , Linda L Carpenter , Christopher J McDougle and Lawrence H Price 1Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 2Department of Psychiatry and Human, Brown Medical School, Mood 3 Disorders Program, Behavior, Butler Hospital, Providence, RI, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA Recently, the addition of drugs with prominent 5-HT2 receptor antagonist properties (risperidone, olanzapine, mirtazapine, and mianserin) to selective serotonin reuptake inhibitors (SSRIs) has been shown to enhance therapeutic responses in patients with major depression and treatment-refractory obsessive–compulsive disorder (OCD). These 5-HT antagonists may also be effective in 2 ameliorating some symptoms associated with autism and other pervasive developmental disorders (PDDs). At the doses used, these drugs would be expected to saturate 5-HT2A receptors. These findings suggest that the simultaneous blockade of 5-HT2A receptors and activation of an unknown constellation of other 5-HT receptors indirectly as a result of 5-HT uptake inhibition might have greater therapeutic efficacy than either action alone. Animal studies have suggested that activation of 5-HT1A and 5-HT2C receptors may counteract the effects of activating 5-HT2A receptors. Additional 5-HT receptors, such as the 5-HT1B/1D/5/7 receptors, may similarly counteract the effects of 5-HT receptor activation. These clinical and preclinical observations suggest that the combination of highly 2A selective 5-HT antagonists and SSRIs, as well as strategies to combine high-potency 5-HT receptor and 5-HT transporter blockade in 2A 2A a single compound, offer the potential for therapeutic advances in a number of neuropsychiatric disorders. -
Study of Methyl Dopa Versus Labetalol in Management of Preeclampsia and Gestational Hypertension
logy & Ob o st ec e tr n i y c s G Dharwadkar et al., Gynecol Obstet (Sunnyvale) 2014, 4:9 Gynecology & Obstetrics DOI; 10.4172/2161-0932.1000242 ISSN: 2161-0932 Research Article Open Access Study of Methyl Dopa Versus Labetalol in Management of Preeclampsia and Gestational Hypertension Dharwadkar MN1, Kanakamma MK1, Dharwadkar SN2*, Rajagopal K1, Gopakumar C3, Divya James Fenn J4 and Balachandar V3,5 1Department of Obstetrics and Gynaecology, Yenepoya Medical College and teaching Hospital, Yenepoya University, Deralakatte, Mangalore, Karnataka 575022, India 2Department of Zoology, K.L.E’s. S. Nijalingappa College, KLE Medical University (Health), Bangalore, Karnataka 560010, India 3Department of Human Genetics Molecular Biology, Bharathiar University, Coimbatore, India 4Post Graduate Student, Department of Obstetrics and Gynaecology, Sree Balaji Medical College and Hospital, Chennai 600044, Tamil Nadu, India 5Human Molecular Genetics Laboratory, Department of Zoology, Bharathiar University, Coimbatore, India Abstract Objective: To assess the efficacy and safety of labetalol compared with methyldopa in the management of mild and moderate cases of pregnancy-induced hypertension (PIH). Methods: Eighty patients with PIH were randomly allocated to receive either labetalol (group A) or methyldopa (group B). Administration of drugs with respect to Age, Gravid Status, Blood Pressure, Urine albumin Levels, Side Effects, Drug dosage, Additional Treatment, Prolongation of Pregnancy, New born Screening Test (NST), mode of termination, Indication of caesarean section, Perinatal safety and APGAR scores were studied. The statistical level of significance was taken at P<0.05. Results: A labetalol has been very effective in control as well as earlier onset of action in patients with methyl dopa.