Opioid Receptor
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A,-, and P-Opioid Receptor Agonists on Excitatory Transmission in Lamina II Neurons of Adult Rat Spinal Cord
The Journal of Neuroscience, August 1994, 74(E): 4965-4971 Inhibitory Actions of S,-, a,-, and p-Opioid Receptor Agonists on Excitatory Transmission in Lamina II Neurons of Adult Rat Spinal Cord Steven R. Glaum,’ Richard J. Miller,’ and Donna L. Hammond* Departments of lPharmacoloaical and Phvsioloqical Sciences and ‘Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois 60637 . This study examined the electrophysiological consequences tor in rat spinal cord and indicate that activation of either of selective activation of 6,-, 6,-, or r-opioid receptors using 6,- or Qopioid receptors inhibits excitatory, glutamatergic whole-cell recordings made from visually identified lamina afferent transmission in the spinal cord. This effect may me- II neurons in thin transverse slices of young adult rat lumbar diate the ability of 6, or 6, receptor agonists to produce an- spinal cord. Excitatory postsynaptic currents (EPSCs) or po- tinociception when administered intrathecally in the rat. tentials (EPSPs) were evoked electrically at the ipsilateral [Key words: DPDPE, deltorphin, spinal cord slice, EPSP, dorsal root entry zone after blocking inhibitory inputs with 6-opioid receptor, DAMGO, naltriben, 7-benzylidene- bicuculline and strychnine, and NMDA receptors with o-2- naltrexone (BNTX), naloxone] amino+phosphonopentanoic acid. Bath application of the p receptor agonist [D-Ala2, KMePhe4, Gly5-ollenkephalin (DAMGO) or the 6, receptor agonist [D-Pen2, o-PerF]en- The dorsal horn of the spinal cord is an important site for the kephalin (DPDPE) produced a log-linear, concentration-de- production of antinociception by K- and 6-opioid receptor ag- pendent reduction in the amplitude of the evoked EPSP/ onists (Yaksh, 1993). -
1 Title Page Pharmacological Comparison of Mitragynine and 7
JPET Fast Forward. Published on December 31, 2020 as DOI: 10.1124/jpet.120.000189 This article has not been copyedited and formatted. The final version may differ from this version. JPET-AR-2020-000189R1: Obeng et al. Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for Mu-Opioid Receptor and Morphine-Like Discriminative-Stimulus Effects in Rats. Title Page Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for Mu-Opioid Receptor and Opioid-Like Behavioral Effects in Rats Samuel Obeng1,2,#, Jenny L. Wilkerson1,#, Francisco León2, Morgan E. Reeves1, Luis F. Restrepo1, Lea R. Gamez-Jimenez1, Avi Patel1, Anna E. Pennington1, Victoria A. Taylor1, Nicholas P. Ho1, Tobias Braun1, John D. Fortner2, Morgan L. Crowley2, Morgan R. Williamson1, Victoria L.C. Pallares1, Marco Mottinelli2, Carolina Lopera-Londoño2, Christopher R. McCurdy2, Lance R. McMahon1, and Takato Hiranita1* Downloaded from Departments of Pharmacodynamics1 and Medicinal Chemistry2, College of Pharmacy, University of Florida jpet.aspetjournals.org #These authors contributed equally Recommended section: Behavioral Pharmacology at ASPET Journals on September 29, 2021 Correspondence: *Takato Hiranita, Ph.D. Department of Pharmacodynamics, College of Pharmacy, University of Florida 1345 Center Drive, Gainesville, FL 32610 Email: [email protected] Phone: +1.352.294.5411 Fax: +1.352.273.7705 Keywords: kratom, mitragynine, 7-hydroxymitragynine, morphine, opioid, discriminative stimulus Conflicts of Interests or Disclaimers: None Manuscript statistics: Number of text pages: 56 Number of tables: 7 Number of figures: 10 Number of supplementary Tables: 4 Number of supplementary figures: 7 1 JPET Fast Forward. Published on December 31, 2020 as DOI: 10.1124/jpet.120.000189 This article has not been copyedited and formatted. -
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. -
Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity Kelly A
International Journal of Neuropsychopharmacology (2018) 21(10): 962–977 doi:10.1093/ijnp/pyy071 Advance Access Publication: August 6, 2018 Review review Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity Kelly A. Berg and William P. Clarke Department of Pharmacology, University of Texas Health, San Antonio, Texas. Correspondence: William P. Clarke, PhD, Department of Pharmacology, Mail Stop 7764, UT Health at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229 ([email protected]). Abstract Constitutive receptor activity/inverse agonism and functional selectivity/biased agonism are 2 concepts in contemporary pharmacology that have major implications for the use of drugs in medicine and research as well as for the processes of new drug development. Traditional receptor theory postulated that receptors in a population are quiescent unless activated by a ligand. Within this framework ligands could act as agonists with various degrees of intrinsic efficacy, or as antagonists with zero intrinsic efficacy. We now know that receptors can be active without an activating ligand and thus display “constitutive” activity. As a result, a new class of ligand was discovered that can reduce the constitutive activity of a receptor. These ligands produce the opposite effect of an agonist and are called inverse agonists. The second topic discussed is functional selectivity, also commonly referred to as biased agonism. Traditional receptor theory also posited that intrinsic efficacy is a single drug property independent of the system in which the drug acts. However, we now know that a drug, acting at a single receptor subtype, can have multiple intrinsic efficacies that differ depending on which of the multiple responses coupled to a receptor is measured. -
Biopharmacy Practice
University of Szeged Biopharmacy practice Editor: Árpád Márki, Ph.D. Authors: Árpád Márki, Ph.D. Adrienn Seres, Ph.D. Anita Sztojkov-Ivanov, Ph.D. Reviewed by: Szilárd Pál, Ph.D. Szeged, 2015. This work is supported by the European Union, co-financed by the European Social Fund, within the framework of "Coordinated, practice-oriented, student-friendly modernization of biomedical education in three Hungarian universities (Pécs, Debrecen, Szeged), with focus on the strengthening of international competitiveness" TÁMOP-4.1.1.C-13/1/KONV-2014-0001 project. The curriculum cannot be sold in any form! Contents Contents ...................................................................................................................................... 2 1. Definitions, routes of drug administration ............................................................................. 6 1.1. Definitions ....................................................................................................................... 6 1.2. Routes of drug administration ......................................................................................... 7 1.3. Questions ....................................................................................................................... 10 2. Receptors .............................................................................................................................. 11 2.1. Definitions .................................................................................................................... -
When Simple Agonism Is Not Enough: Emerging Modalities of GPCR Ligands Nicola J
When simple agonism is not enough: emerging modalities of GPCR ligands Nicola J. Smith, Kirstie A. Bennett, Graeme Milligan To cite this version: Nicola J. Smith, Kirstie A. Bennett, Graeme Milligan. When simple agonism is not enough: emerging modalities of GPCR ligands. Molecular and Cellular Endocrinology, Elsevier, 2010, 331 (2), pp.241. 10.1016/j.mce.2010.07.009. hal-00654484 HAL Id: hal-00654484 https://hal.archives-ouvertes.fr/hal-00654484 Submitted on 22 Dec 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Accepted Manuscript Title: When simple agonism is not enough: emerging modalities of GPCR ligands Authors: Nicola J. Smith, Kirstie A. Bennett, Graeme Milligan PII: S0303-7207(10)00370-9 DOI: doi:10.1016/j.mce.2010.07.009 Reference: MCE 7596 To appear in: Molecular and Cellular Endocrinology Received date: 15-1-2010 Revised date: 15-6-2010 Accepted date: 13-7-2010 Please cite this article as: Smith, N.J., Bennett, K.A., Milligan, G., When simple agonism is not enough: emerging modalities of GPCR ligands, Molecular and Cellular Endocrinology (2010), doi:10.1016/j.mce.2010.07.009 This is a PDF file of an unedited manuscript that has been accepted for publication. -
Drug Action-Receptor Theory
Drug action-Receptor Theory Molecules (eg, drugs, hormones, neurotransmitters) that bind to a receptor are called ligands. The binding can be specific and reversible. A ligand may activate or inactivate a receptor; activation may increase or decrease a particular cell function. Each ligand may interact with multiple receptor subtypes. Few if any drugs are absolutely specific for one receptor or subtype, but most have relative selectivity. Selectivity is the degree to which a drug acts on a given site relative to other sites; selectivity relates largely to physicochemical binding of the drug to cellular receptors. A drug’s ability to affect a given receptor is related to the drug’s affinity (probability of the drug occupying a receptor at any given instant) and intrinsic efficacy (intrinsic activity—degree to which a ligand activates receptors and leads to cellular response). A drug’s affinity and activity are determined by its chemical structure. The pharmacologic effect is also determined by the duration of time that the drug-receptor complex persists (residence time). The lifetime of the drug-receptor complex is affected by dynamic processes (conformation changes) that control the rate of drug association and dissociation from the target. A longer residence time explains a prolonged pharmacologic effect. Drugs with long residence times include finasteride and darunavir. A longer residence time can be a potential disadvantage when it prolongs a drug's toxicity. For some receptors, transient drug occupancy produces the desired pharmacologic effect, whereas prolonged occupancy causes toxicity. Ability to bind to a receptor is influenced by external factors as well as by intracellular regulatory mechanisms. -
Heterodimerization of Μ and Δ Opioid Receptors: a Role in Opiate Synergy
The Journal of Neuroscience, 2000, Vol. 20 RC110 1of5 Heterodimerization of and ␦ Opioid Receptors: A Role in Opiate Synergy I. Gomes, B. A. Jordan, A. Gupta, N. Trapaidze, V. Nagy, and L. A. Devi Departments of Pharmacology and Anesthesiology, New York University School of Medicine, New York, New York 10016 Opiate analgesics are widely used in the treatment of severe -selective ligands results in a significant increase in the bind- pain. Because of their importance in therapy, different strate- ing of a ␦ receptor agonist. This robust increase is also seen in gies have been considered for making opiates more effective SKNSH cells that endogenously express both and ␦ recep- while curbing their liability to be abused. Although most opiates tors. Furthermore, we find that a ␦ receptor antagonist en- exert their analgesic effects primarily via opioid receptors, a hances both the potency and efficacy of the receptor signal- number of studies have shown that ␦ receptor-selective drugs ing; likewise a antagonist enhances the potency and efficacy can enhance their potency. The molecular basis for these find- of the ␦ receptor signaling. A combination of agonists ( and ␦ ings has not been elucidated previously. In the present study, receptor selective) also synergistically binds and potentiates we examined whether heterodimerization of and ␦ receptors signaling by activating the –␦ heterodimer. Taken together, could account for the cross-modulation previously observed these studies show that heterodimers exhibit distinct ligand between these two receptors. We find that co-expression of binding and signaling characteristics. These findings have im- and ␦ receptors in heterologous cells followed by selective portant clinical ramifications and may provide new foundations immunoprecipitation results in the isolation of –␦ het- for more effective therapies. -
Biased Receptor Functionality Versus Biased Agonism in G-Protein-Coupled Receptors Journal Xyz 2017; 1 (2): 122–135
BioMol Concepts 2018; 9: 143–154 Review Open Access Rafael Franco*, David Aguinaga, Jasmina Jiménez, Jaume Lillo, Eva Martínez-Pinilla*#, Gemma Navarro# Biased receptor functionality versus biased agonism in G-protein-coupled receptors Journal xyz 2017; 1 (2): 122–135 https://doi.org/10.1515/bmc-2018-0013 b-arrestins or calcium sensors are also provided. Each of receivedThe FirstJuly 19, Decade 2018; accepted (1964-1972) November 2, 2018. the functional GPCR units (which are finite in number) has Abstract:Research Functional Article selectivity is a property of G-protein- a specific conformation. Binding of agonist to a specific coupled receptors (GPCRs) by which activation by conformation, i.e. GPCR activation, is sensitive to the differentMax Musterman, agonists leads Paul to differentPlaceholder signal transduction kinetics of the agonist-receptor interactions. All these mechanisms. This phenomenon is also known as biased players are involved in the contrasting outputs obtained agonismWhat and Is has So attracted Different the interest Aboutof drug discovery when different agonists are assayed. programsNeuroenhancement? in both academy and industry. This relatively recent concept has raised concerns as to the validity and Keywords: conformational landscape; GPCR heteromer; realWas translational ist so value anders of the results am showing Neuroenhancement? bias; firstly cytocrin; effectors; dimer; oligomer; structure. biased agonism may vary significantly depending on the cellPharmacological type and the experimental and Mental constraints, -
NIDA Drug Supply Program Catalog, 25Th Edition
RESEARCH RESOURCES DRUG SUPPLY PROGRAM CATALOG 25TH EDITION MAY 2016 CHEMISTRY AND PHARMACEUTICS BRANCH DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES NATIONAL INSTITUTE ON DRUG ABUSE NATIONAL INSTITUTES OF HEALTH DEPARTMENT OF HEALTH AND HUMAN SERVICES 6001 EXECUTIVE BOULEVARD ROCKVILLE, MARYLAND 20852 160524 On the cover: CPK rendering of nalfurafine. TABLE OF CONTENTS A. Introduction ................................................................................................1 B. NIDA Drug Supply Program (DSP) Ordering Guidelines ..........................3 C. Drug Request Checklist .............................................................................8 D. Sample DEA Order Form 222 ....................................................................9 E. Supply & Analysis of Standard Solutions of Δ9-THC ..............................10 F. Alternate Sources for Peptides ...............................................................11 G. Instructions for Analytical Services .........................................................12 H. X-Ray Diffraction Analysis of Compounds .............................................13 I. Nicotine Research Cigarettes Drug Supply Program .............................16 J. Ordering Guidelines for Nicotine Research Cigarettes (NRCs)..............18 K. Ordering Guidelines for Marijuana and Marijuana Cigarettes ................21 L. Important Addresses, Telephone & Fax Numbers ..................................24 M. Available Drugs, Compounds, and Dosage Forms ..............................25 -
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 ........................................... -
Self-Administration of Morphine, DAMGO, and DPDPE Into the Ventral Tegmental Area of Rats
The Journal of Neuroscmce, April 1994. 74(4). 1978-1984 Self-Administration of Morphine, DAMGO, and DPDPE into the Ventral Tegmental Area of Rats- Darragh P. Devine and Roy A. Wise Center for Studies In Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada H3G lM8 Intracranial self-administration of K- and &opioid agonists ment associated with prior drug exposure. Conditioned place was demonstrated in male Long-Evans rats. Independent preferences are also observed after VTA microinjections of the groups were allowed to lever-press for ventral tegmental enkephalinasc inhibitor thiorphan (Glimcher et al., 1984). In area (VTA) microinfusions of morphine, the selective /* ag- addition, VT.4 microinjections ofmorphine lower the threshold onist [D-Ala*,N-Me-Phe4-GIy5-ol]-enkephalin (DAMGO), the for rewarding electrical stimulation of the lateral hypothalamus selective &agonist [o-Pen’,o-Pens]-enkephalin (DPDPE), or (Brockkamp et al., 1976; Jenck et al., 1987). ineffective drug vehicle. Morphine, DAMGO, and DPDPE were There arc at least three major types of opioid receptors (II, 6, each effective in establishing and maintaining lever-press- and K: Gilbert and Martin, 1976: Martin et al.. 1976; Lord et ing habits. Lever-pressing responses were extinguished al.: 1977; Paterson et al., 1983) that could potentially be in- during a session when vehicle was substituted for drug, and \-ol\,ed in the reuarding effects of opiates. The tritiated y agonist reinstated when drug reinforcement was reestablished. Thus, ‘H-DAMGO labels a dense population of FL-opioid receptors in it appears that VTA CL- and &opioid receptors are each in- the VTA (Quirion ct al.