Home LiteratureArticle Details
PMID: 17700724 Published · ppublish English Journal Article Review

Pharmacological onomastics: what's in a name?

British journal of pharmacology ·Vol. 153 ·No. 3 ·2008-02-00 ·Pages 432-8

Kenakin TP

Abstract

Drugs are named for their primary receptor target and overt action (agonism, antagonism) but the observation of multiple or collateral efficacies emanating from drugs activating a single receptor target is posing a challenge for drug classification and nomenclature. With increasing abilities to detect alteration in cellular function has come the identification of efficacies that are not necessarily manifest in obvious changes in cell response. Specifically, some agonists selectively activate cellular pathways, demonstrate phenotypic behaviour associated with cell type and some antagonists actively induce receptor internalization without activation. In addition, the effects of allosteric modulators can be linked to the nature of the co-binding ligand posing a similar complication in classification and naming. Thus, accurate labels for this new generation of selective drugs may require identification of receptor partners (G-protein type, beta-arrestin) or pathway or, in the case of allosteric modulators, identification of co-binding ligands. The association of distinct phenotypic behaviours with molecules opens the opportunity to better associate clinical effects with distinct pharmacological properties.

MeSH Terms
Allosteric Regulation Drug Agonism Drug Antagonism Drug Delivery Systems/classification Humans Ligands Pharmaceutical Preparations/classification Terminology as Topic
Chemicals
Ligands Pharmaceutical Preparations
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kenakin T P
Biochemical and Cellular Targets, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA. Terry.P.Kenakin@gsk.com
References (52)
52 references, click to expand
  1. The use of stimulus-biased assay systems to detect agonist-specific receptor active states: implications for the trafficking of receptor stimulus by agonists.
    Mol Pharmacol. 2000 Dec;58(6):1230-8 PMID: 11093758
  2. Agonist-receptor efficacy. II. Agonist trafficking of receptor signals.
    Trends Pharmacol Sci. 1995 Jul;16(7):232-8 PMID: 7667897
  3. Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11406-11 PMID: 13679574
  4. Receptor activity-independent recruitment of betaarrestin2 reveals specific signalling modes.
    EMBO J. 2004 Oct 13;23(20):3950-61 PMID: 15385966
  5. What's next in translational medicine?
    Clin Sci (Lond). 2007 Feb;112(4):217-27 PMID: 17223795
  6. Achieving signalling selectivity of ligands for the corticotropin-releasing factor type 1 receptor by modifying the agonist's signalling domain.
    Br J Pharmacol. 2007 Jul;151(6):851-9 PMID: 17533422
  7. Drug efficacy at G protein-coupled receptors.
    Annu Rev Pharmacol Toxicol. 2002;42:349-79 PMID: 11807176
  8. Pharmacological proteus?
    Trends Pharmacol Sci. 1995 Aug;16(8):256-8 PMID: 7482982
  9. Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions.
    Mol Pharmacol. 2005 Jun;67(6):2016-24 PMID: 15749995
  10. Bombesin and substance P analogues differentially regulate G-protein coupling to the bombesin receptor. Direct evidence for biased agonism.
    J Biol Chem. 2001 Jul 27;276(30):28083-91 PMID: 11323408
  11. An opioid agonist that does not induce mu-opioid receptor--arrestin interactions or receptor internalization.
    Mol Pharmacol. 2007 Feb;71(2):549-57 PMID: 17090705
  12. Chemokine blockers--therapeutics in the making?
    Trends Pharmacol Sci. 2006 Jan;27(1):41-7 PMID: 16310864
  13. The new generation of antipsychotic drugs: how atypical are they?
    Int J Neuropsychopharmacol. 2000 Dec;3(4):339-349 PMID: 11343614
  14. Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.
    Mol Pharmacol. 1997 Jul;52(1):172-9 PMID: 9224827
  15. The ligand paradox between affinity and efficacy: can you be there and not make a difference?
    Trends Pharmacol Sci. 2002 Jun;23(6):275-80 PMID: 12084633
  16. Fluorescent labeling of purified beta 2 adrenergic receptor. Evidence for ligand-specific conformational changes.
    J Biol Chem. 1995 Nov 24;270(47):28268-75 PMID: 7499324
  17. The CCR5 receptor-based mechanism of action of 873140, a potent allosteric noncompetitive HIV entry inhibitor.
    Mol Pharmacol. 2005 Apr;67(4):1268-82 PMID: 15644495
  18. Historical review: a brief history and personal retrospective of seven-transmembrane receptors.
    Trends Pharmacol Sci. 2004 Aug;25(8):413-22 PMID: 15276710
  19. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation.
    J Biol Chem. 2006 Apr 21;281(16):10856-64 PMID: 16492667
  20. Opioid receptors are coupled tightly to G proteins but loosely to adenylate cyclase in NG108-15 cell membranes.
    Mol Pharmacol. 1988 Dec;34(6):744-54 PMID: 2849042
  21. Inverse, protean, and ligand-selective agonism: matters of receptor conformation.
    FASEB J. 2001 Mar;15(3):598-611 PMID: 11259378
  22. Oligomerization of G-protein-coupled transmitter receptors.
    Nat Rev Neurosci. 2001 Apr;2(4):274-86 PMID: 11283750
  23. Functional selectivity and classical concepts of quantitative pharmacology.
    J Pharmacol Exp Ther. 2007 Jan;320(1):1-13 PMID: 16803859
  24. Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors.
    Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6802-7 PMID: 8692899
  25. Composition and function of g protein-coupled receptor signalsomes controlling mitogen-activated protein kinase activity.
    J Mol Neurosci. 2005;26(2-3):253-64 PMID: 16012199
  26. Agonist and inverse agonist actions of beta-blockers at the human beta 2-adrenoceptor provide evidence for agonist-directed signaling.
    Mol Pharmacol. 2003 Dec;64(6):1357-69 PMID: 14645666
  27. Sequential binding of agonists to the beta2 adrenoceptor. Kinetic evidence for intermediate conformational states.
    J Biol Chem. 2004 Jan 2;279(1):686-91 PMID: 14559905
  28. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy.
    Mol Pharmacol. 2006 Nov;70(5):1575-84 PMID: 16901982
  29. Ago-antagonist muscle spindle inputs contribute together to joint movement coding in man.
    Brain Res. 1998 Apr 27;791(1-2):167-76 PMID: 9593876
  30. Agonist-induced modulation of inverse agonist efficacy at the beta 2-adrenergic receptor.
    Mol Pharmacol. 1996 Sep;50(3):662-9 PMID: 8794908
  31. Agonist efficacy and allosteric models of receptor action.
    Ann N Y Acad Sci. 1997 May 30;812:98-115 PMID: 9508759
  32. Collateral efficacy as a pharmacological problem applied to new drug discovery.
    Expert Opin Drug Discov. 2006 Dec;1(7):635-52 PMID: 23495990
  33. Efficacy as a vector: the relative prevalence and paucity of inverse agonism.
    Mol Pharmacol. 2004 Jan;65(1):2-11 PMID: 14722230
  34. Inverse agonism and the regulation of receptor number.
    Trends Pharmacol Sci. 1997 Dec;18(12):468-74 PMID: 9458695
  35. Clozapine and other 5-hydroxytryptamine-2A receptor antagonists alter the subcellular distribution of 5-hydroxytryptamine-2A receptors in vitro and in vivo.
    Neuroscience. 1999;91(2):599-606 PMID: 10366017
  36. Inhibitory effect of oxytocin on corticotrope function in humans: are vasopressin and oxytocin ying-yang neurohormones?
    Psychoneuroendocrinology. 2001 Oct;26(7):649-55 PMID: 11500247
  37. Transduction of receptor signals by beta-arrestins.
    Science. 2005 Apr 22;308(5721):512-7 PMID: 15845844
  38. Selective and divergent regulation of cortical 5-HT(2A) receptors in rabbit.
    J Pharmacol Exp Ther. 2001 Dec;299(3):1066-72 PMID: 11714896
  39. Technology Insight: modern methods to monitor protein-protein interactions reveal functional TSH receptor oligomerization.
    Nat Clin Pract Endocrinol Metab. 2007 Feb;3(2):180-90 PMID: 17237844
  40. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors.
    J Recept Signal Transduct Res. 2006;26(1-2):107-28 PMID: 16595341
  41. Identification of allosteric peptide agonists of CXCR4.
    J Biol Chem. 2003 Jan 10;278(2):896-907 PMID: 12417595
  42. Tracking the opioid receptors on the way of desensitization.
    Cell Signal. 2006 Nov;18(11):1815-33 PMID: 16750901
  43. The neurokinin A receptor activates calcium and cAMP responses through distinct conformational states.
    J Biol Chem. 2001 Sep 14;276(37):34853-61 PMID: 11459843
  44. The fluorescent toolbox for assessing protein location and function.
    Science. 2006 Apr 14;312(5771):217-24 PMID: 16614209
  45. Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET).
    Nat Methods. 2006 Mar;3(3):165-74 PMID: 16489332
  46. Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists.
    Brain Res Bull. 2001 Nov 15;56(5):441-51 PMID: 11750789
  47. New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors.
    Mol Cell. 2006 Dec 8;24(5):643-52 PMID: 17157248
  48. Antagonists with negative intrinsic activity at delta opioid receptors coupled to GTP-binding proteins.
    Proc Natl Acad Sci U S A. 1989 Oct;86(19):7321-5 PMID: 2552439
  49. Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta 2 adrenergic receptor.
    J Biol Chem. 2001 Jul 6;276(27):24433-6 PMID: 11320077
  50. The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis.
    J Biol Chem. 2001 Mar 16;276(11):8269-77 PMID: 11069907
  51. Protein biosensors based on the principle of fluorescence resonance energy transfer for monitoring cellular dynamics.
    Biotechnol Lett. 2006 Dec;28(24):1971-82 PMID: 17021660
  52. A modification of receptor theory.
    Br J Pharmacol Chemother. 1956 Dec;11(4):379-93 PMID: 13383117
Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
Published
2008-02-00
Epub
2007-00-13
Pages
432-8
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2241801
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com