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Encyclopedia > Receptor antagonist
Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling.
Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling.

A receptor antagonist is a drug that does not provoke a biological response itself upon binding to a receptor, but blocks or attenuates agonist-mediated responses.[1] In pharmacology an antagonist is a binding partner (ligand) of a receptor by disrupting the interaction and inhibiting the function of an agonist or inverse agonist at their receptors. Antagonists are said to have affinity but no efficacy for their cognate receptors. The majority of drug antagonists and inhibitors achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites.[2] Image File history File links Antagonist. ... Image File history File links Antagonist. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... Pharmacology (in Greek: pharmakon (φάρμακον) meaning drug, and lego (λέγω) to tell (about)) is the study of how drugs interact with living organisms to produce a change in function. ... It has been suggested that this article or section be merged with ligand. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor but exerts the opposite pharmacological effect. ... In chemistry and biochemistry, a dissociation constant or an ionization constant is a specific type of equilibrium constant used for reversible reactions or processes. ... Efficacy is the ability to produce a desired amount of a desired effect. ...

Contents

Receptors

Main article: Receptor (biochemistry)

Biochemical receptors are large molecules (usually proteins) that can be activated by a binding of a ligand (such as a hormone or drug).[3] Receptors can be membrane-bound occurring on the cell membrane of cells or intracellular as for hormone-receptors. Binding occurs as a result of noncovalent interaction between the receptor and its ligand, at locations called the binding site on the receptor. A receptor may contain one or more binding sites for different ligands. Binding to the active or orthostatic site on the receptor regulates receptor activation directly.[3] The activity of receptors can also be regulated by binding of a ligand to other sites on the receptor termed allosteric sites.[4] Antagonists mediate their affects through receptor interactions by preventing agonist-induced responses. This may be accomplished by binding to the active site or at the allosteric site.[5] In addition, antagonists may interact at unique binding sites not normally involved in the biological regulation of the receptor's activity to exert their affects.[5][6] In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... It has been suggested that this article or section be merged with ligand. ... For other uses, see Hormone (disambiguation). ... For other uses, see Drug (disambiguation). ... Noncovalent bonding refers to a variety of interactions, that are not covalent in nature, between molecules or parts of molecules that provide force to hold the molecules or parts of molecules together usually in a specific orientation or conformation. ... A binding site is a region on a protein to which specific ligands bind. ...


The term antagonist was originally coined to describe different profiles of drug effects.[7] The biochemical definition of a receptor antagonist was introduced by Ariens[8] and Stephanson[9] in the 1950s. The current accepted definition of receptor antagonist is based on the receptor occupancy model. It narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn "on" a single cellular response by binding to the receptor, thus initiating a biochemical mechanism for change within a cell. Antagonists were thought to turn "off" that response by 'blocking' the receptor from the agonist. This definition also remains in use for physiological antagonists, substances which have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by β-adrenergic receptor activation. Receptor theory is a theory that explains the mechanism of receptor activation and describes models which seek to accurately explain drug affects. ... Physiological agonism and antagonism is the mechanism of substances to induce the same ultimate effects in the body as other substances, as if they were receptor agonists or antagonists, but without binding to the same receptor. ... This article or section does not cite any references or sources. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search The H1 receptor is a histamine receptor, and thus an important target for clinically important drugs, and is likely one of the most important receptors for modulating mammalian circadian cycles. ... Epinephrine (INN) or adrenaline (BAN) is a hormone and a neurotransmitter. ... Epinephrine Norepinephrine The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. ...


Our understanding of the mechanism of drug induced receptor activation and receptor theory and the biochemical definition of a receptor antagonist continues to evolve. The two state model of receptor activation has given way to multistate models with intermediate conformational states.[10] The discovery of functional selectivity and that ligand-specific receptor conformations occur and can affect interaction of receptors with different second messenger systems may mean that drugs can be designed to activate some of the downstream functions of a receptor but not others.[11] The theory alters the view that efficacy at a receptor is receptor-independent property of a drug and that efficacy may actually depend on where that receptor is expressed.[11] Receptor theory is a theory that explains the mechanism of receptor activation and describes models which seek to accurately explain drug affects. ... Recently, a novel theory called Functional Selectivity (also referred to in the literature as “agonist trafficking”, “biased agonism”, “differential engagement” and “protean agonism”) has been proposed to broaden conventional definitions of pharmacology. ... Efficacy is the ability to produce a desired amount of a desired effect. ...


Pharmacodynamics

Main article: pharmacodynamics

Pharmacodynamics is the study of the biochemical and physiological effects of drugs and the mechanisms of drug action and the relationship between drug concentration and effect. ...

Efficacy and potency

By definition antagonists display no efficacy,[9] the ability to activate a receptor once bound, however they inhibit the function of other drug classes namely agonists, inverse agonists and partial agonists. In functional antagonist assays a dose-response curve which measures the effect the ability of a range of concentrations of antagonists to reverse the activity of an agonist.[3] The potency of an antagonist is usually defined by its IC50 value. This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist. Elucidating an IC50 value is useful for comparing the potency of drugs with similar efficacies however the dose-response curves produced by both drug antagonists must be similar.[12] The lower the IC50, the greater the potency of the antagonist the lower the concentration of drug that is required to inhibit the maximum biological response. Lower concentrations of drugs may be associated with fewer side effects associated with that drug.[13] Efficacy is the ability to produce a desired amount of a desired effect. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor but exerts the opposite pharmacological effect. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... A dose-response curve is a simple X-Y graph with Y usually being the measured dose (usually in milligrams, micrograms, or grams per kilogram of body-wieght) and X being the response. ... Potency may refer to: Virility Lack of the above: Erectile dysfunction, Infertility or Effeminacy. ... IC50, or the half maximal inhibitory concentration, represents the concentration of an inhibitor that is required for 50% inhibition of its target (i. ...


Affinity

The affinity of an antagonist for its binding site ki or ability to bind a receptor will determine the duration of inhibition of agonist activity. The affinity of an antagonists can be determined experimentally using Schild regression or for competitive antagonists in radioligand binding studies using the Cheng-Prusoff equation. Schild regression can be used to determine the nature of antagonism as beginning either competitive or non-competitive and ki determination is independent of the affinity, efficacy or concentration of the agonist used. However it is important that equilibrium has been reached. The effects of receptor desensitization on reaching equilibrium must also be taken into account. The affinity constant of antagonists exhibiting two or more effects such as competitive neuromuscular-blocking agents which also block ion channels as well as antagonising agonist binding cannot be analysed using schild regression [14][15] Schild regression involves comparing the change in the dose ratio, the ratio of the EC50 of an agonist alone compared to the EC50 in the presence of a competitive antagonist as determined on a dose response curve. Altering the amount of antagonist used in the assay can alter the dose ratio. In Schild regression a plot is made of the log(dose ratio-1) versus the log concentration of antagonist for a range of antagonist concentrations.[16] The affinity or ki is where the line cuts the x-axis on the regression plot. Whereas with Schild regression antagonist concentration is varied in experiments used to derive ki values from the Cheng-Prusoff equation agonist concentrations are varied. Affinity for competitive agonists and antagonists is related by the Cheng-Prusoff factor used to calculate the Ki(affinity constant for an antagonist) from the shift in IC50 that occurs during competitive inhibition.[17] The Cheng-Prusoff factor takes into account the effect of altering agonist concentration and agonist affinity for the recepor on inhibition produced by competitive antagonists.[13] A binding site is a region on a protein to which specific ligands bind. ... This article or section is in need of attention from an expert on the subject. ... IC50, or the half maximal inhibitory concentration, represents the concentration of an inhibitor that is required for 50% inhibition of its target (i. ...


Types of antagonists

Competitive

Competitive antagonists reversibly bind to receptors at the same binding site the active site as the endogenous ligand or agonist, but without activating the receptor. Agonists and antagonists "compete" for the same binding site on the receptor. Once bound, an antagonist will block agonist binding. The level of activity of the receptor will be determined by the relative affinity of each molecule for the site and their relative concentrations. High concentrations of a competitive agonist will increase the proportion of receptors which the agonist occupies, higher concentrations of the antagonist will be required to obtain the same degree of binding-site occupancy.[13] In functional assays using competitive antagonists a parallel rightward shifts of agonist dose–response curves with no alteration of the maximal response is observed.[18] The interleukin-1 receptor antagonist, IL-1Ra is an example of a cometitive antagonist.[19] The effects of a competitive antagonist may be overcome by increasing the concentration of agonist. Often (though not always) these antagonists possess a very similar chemical structure to that of the agonist. A competitive antagonist is a receptor antagonist which binds to a receptor but fails to activate it. ... A binding site is a region on a protein to which specific ligands bind. ... Look up affinity in Wiktionary, the free dictionary. ... Interleukin-1 (IL-1) is one of the first cytokines ever described. ... interleukin 1 receptor antagonist, the natural antagonist of the pro-inflammatory cytokines interleukin-1alpha, interleukin-1beta Categories: Wikipedia cleanup | Biochemistry stubs ...


Non-competitive

Non-competitive antagonists are also known as allosteric antagonist. These antagonists bind to a distinctly separate binding site from the agonist, exerting their action to that receptor via the other binding site. Cyclothiazide has been shown to act as a reversible non-competitive antagonist of mGluR1 receptor.[20] Thus they do not compete with agonists for binding. The bound antagonists may result in a decreased affinity of an agonist for that receptor, or alternatively may prevent conformational changes in the receptor required for receptor activation after the agonist binds.[21] No amount of agonist can completely overcome the inhibition once it has been established. In functional assays of non-competitive antagonists depression of the maximal response of agonist dose-response curves and in some cases rightward shifts is produced.[18] The rightward shift will occur as a result of a receptor reserve[9] and inhibition of the agonist response will only occur when this reserve is depleated. In biochemistry, an enzyme or other protein is allosteric if its activity or efficiency changes in response to the binding of an effector molecule at a so-called allosteric site. ... Metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor which are active through an indirect metabotropic process. ...


Uncompetitive

Uncompetivite antagonists differ from non-competitive antagonists in that they require receptor activation by an agonist before binding can occur to the separate allosteric binding site of the antagonist. This type of antagonism produces a kinetic profile in which "the same amount of antagonist blocks higher concentrations of agonist better than lower concentrations of agonist".[22] Memantine, used in the treatment of Alzheimer's disease, is an uncompetitive antagonist of the NMDA receptor.[23] Memantine is the first in a novel class of Alzheimers disease medications acting on the glutamatergic system. ... The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA (N-methyl d-aspartate) is a name of its selective specific agonist). ...


Partial agonists and inverse agonists

Partial agonists are defined as drugs which at a given receptor might differ in the amplitude of the functional response that they elicit after maximal receptor occupancy. Although they are agonists, partial agonist can act as a competitive antagonist if co-administered with a full agonist, as it competes with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone.[24][25] Clinically, their usefulness is derived from their ability to enhance deficient systems while simultaneously blocking excessive activity. Exposing a receptor to a high level of the partial agonist will ensure that it has a constant, weak level of activity whether its normal agonist is present at high or low levels. In addition, it has been suggested that partial agonism prevents the adaptive regulatory mechanisms that frequently develop after repeated exposure to potent full agonists or antagonists.[26][27] Buprenorphine a partial agonist of the μ-opioid receptor binding it with weak morphine-like activity and is used clinically as an analgesic in pain management and in reversing morphine addiction as an alternative to methodone in the treatment of drug addiction.[28] Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... A competitive antagonist is a receptor antagonist which binds to a receptor but fails to activate it. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... Buprenorphine, is an opioid drug with partial agonist and antagonist actions. ... Opioid receptors are a group of G-protein coupled receptors with opioids as ligands. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... Methadone is a synthetic opioid, used medically as an analgesic and anti-addictive. ...


An inverse agonist can have effects similar to an antagonist, but causes a distinct set of downstream biological responses. Contitutively active receptors which exhibit intrinsic or basal activity can have inverse agonists, which not only block the effects of binding agonists like a classical antagonist, but inhibit the basal activity of the receptor. Drugs previously classified as antagonists are now beginning to be reclassified as inverse agonists because of the discovery of constitutive active receptors.[29][30] Antihistamines, originally classified as antagonists of histamine H1 receptors have been reclassified as inverse agonists.[31] In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor but exerts the opposite pharmacological effect. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... An H1 antihistamine is a histamine antagonist which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions, through action at the H1 receptor. ... This article or section does not cite any references or sources. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search The H1 receptor is a histamine receptor, and thus an important target for clinically important drugs, and is likely one of the most important receptors for modulating mammalian circadian cycles. ...


Antagonist reversibility

Many antagonists are considered reversible antagonists because they, like most agonists, will bind and unbind a receptor at rates determined by the receptor-ligand kinetics. In biochemistry, receptor-ligand kinetics is a branch of chemical kinetics in which the kinetic species are defined by different non-covalent bindings and/or conformations of the molecules involved, which are denoted as receptor(s) and ligand(s). ...


Irreversible antagonists covalently bind to the receptor target and generally cannot be removed; inactivating the receptor the duration of the antagonist effects is determined by the rate of receptor turnover, the rate of synthesis of new receptors. Phenoxybenzamine is an example of an irreversible alpha blocker—it permanently binds to α adrenergic receptors, preventing adrenaline and noradrenaline from binding.[32] Inactivation of receptors normally results in a depression of the maximal response of agonist-dose response curves and right shift in the curve occurs where there is a receptor reserve similar to non-competitive antagonists. A washout step in the assay will usually distinguish between non-competitive and irreversible antagonist drugs as effects of non-competitive antagonists are reversible and activity of agonist will be restored. Covalent redirects here. ... Phenoxybenzamine is a non-specific, irreversible alpha blocker used in the treatment of hypertension, and specifically that caused by pheochromocytoma. ... Alpha blockers (also called alpha-adrenergic blocking agents) constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles. ... Epinephrine Norepinephrine The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. ... Epinephrine Norepinephrine The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. ... Epinephrine (INN) or adrenaline (BAN) is a hormone and a neurotransmitter. ... Norepinephrine, known as noradrenaline outside the USA, is a catecholamine and a phenethylamine with chemical formula C8H11NO3. ...


Competitive irreversible antagonists like competitive antagonists also involves competition between agonist and antagonists of the receptor but stronger binding forces, usually involving covalent binding of the antagonist to the agonist binding site on the receptor,[12] in which case there is a period before the covalent bond forms determined by receptor-ligand kinetics during which competing ligands can prevent the inhibition. Once binding of the antagonist occurs however even at high agonist concentrations the effect of the antagonist cannot be fully reversed. As for non-competitive antagonists and irreversible antagonists in functional assays with irreversible competitive antagonist drugs there may be a shift in the log concentration–effect curve to the right but generally both a decrease in slope and reduced maximum are obtained.[12]


See also

Receptor theory is a theory that explains the mechanism of receptor activation and describes models which seek to accurately explain drug affects. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ... HIV protease in a complex with the protease inhibitor ritonavir. ... In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor but exerts the opposite pharmacological effect. ... Efficacy is the ability to produce a desired amount of a desired effect. ... In chemistry and biochemistry, a dissociation constant or an ionization constant is a specific type of equilibrium constant used for reversible reactions or processes. ...

References

  1. ^ "Pharmacology Guide: In vitro pharmacology: concentration-response curves." GlaxoWellcome. Retrieved on December 6, 2007.
  2. ^ Hopkins AL, Groom CR (2002). "The druggable genome". Nature reviews. Drug discovery 1 (9): 727–30. doi:10.1038/nrd892. PMID 12209152. 
  3. ^ a b c T. Kenakin (2006) A Pharmacology Primer: Theory, Applications, and Methods. 2nd Edition Elsevier ISBN 0123705991
  4. ^ May LT, Avlani VA, Sexton PM, Christopoulos A (2004). "Allosteric modulation of G protein-coupled receptors". Curr. Pharm. Des. 10 (17): 2003–13. PMID 15279541. 
  5. ^ a b Christopoulos A (2002). "Allosteric binding sites on cell-surface receptors: novel targets for drug discovery". Nature reviews. Drug discovery 1 (3): 198–210. PMID 12120504. 
  6. ^ Rees S, Morrow D, Kenakin T (2002). "GPCR drug discovery through the exploitation of allosteric drug binding sites". Recept. Channels 8 (5-6): 261–8. PMID 12690954. 
  7. ^ Negus SS (2006). "Some implications of receptor theory for in vivo assessment of agonists, antagonists and inverse agonists". Biochem. Pharmacol. 71 (12): 1663–70. doi:10.1016/j.bcp.2005.12.038. PMID 16460689. 
  8. ^ ARIENS EJ (1954). "Affinity and intrinsic activity in the theory of competitive inhibition. I. Problems and theory". Archives internationales de pharmacodynamie et de thérapie 99 (1): 32–49. PMID 13229418. 
  9. ^ a b c Stephenson RP (1997). "A modification of receptor theory. 1956". Br. J. Pharmacol. 120 (4 Suppl): 106–20; discussion 103–5. PMID 9142399. 
  10. ^ Vauquelin G, Van Liefde I (2005). "G protein-coupled receptors: a count of 1001 conformations". Fundamental & clinical pharmacology 19 (1): 45–56. doi:10.1111/j.1472-8206.2005.00319.x. PMID 15660959. 
  11. ^ a b Urban JD, Clarke WP, von Zastrow M, et al (2007). "Functional selectivity and classical concepts of quantitative pharmacology". J. Pharmacol. Exp. Ther. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859. 
  12. ^ a b c Lees P, Cunningham FM, Elliott J (2004). "Principles of pharmacodynamics and their applications in veterinary pharmacology". J. Vet. Pharmacol. Ther. 27 (6): 397–414. doi:10.1111/j.1365-2885.2004.00620.x. PMID 15601436. 
  13. ^ a b c Swinney DC (2004). "Biochemical mechanisms of drug action: what does it take for success?". Nature reviews. Drug discovery 3 (9): 801–8. doi:10.1038/nrd1500. PMID 15340390. 
  14. ^ Wyllie DJ, Chen PE (2007). "Taking the time to study competitive antagonism". Br. J. Pharmacol. 150 (5): 541–51. doi:10.1038/sj.bjp.0706997. PMID 17245371. 
  15. ^ Colquhoun D (2007). "Why the Schild method is better than Schild realised". Trends Pharmacol Sci. doi:10.1016/j.tips.2007.09.011. PMID 18023486. 
  16. ^ Schild HO (1975). "An ambiguity in receptor theory". Br. J. Pharmacol. 53 (2): 311. PMID 1148491. 
  17. ^ Cheng Y, Prusoff WH (1973). "Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction". Biochem. Pharmacol. 22 (23): 3099–108. PMID 4202581. 
  18. ^ a b Vauquelin G, Van Liefde I, Birzbier BB, Vanderheyden PM (2002). "New insights in insurmountable antagonism". Fundamental & clinical pharmacology 16 (4): 263–72. PMID 12570014. 
  19. ^ Arend WP (1993). "Interleukin-1 receptor antagonist". Adv. Immunol. 54: 167–227. PMID 8379462. 
  20. ^ Surin A, Pshenichkin S, Grajkowska E, Surina E, Wroblewski JT (2007). "Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists". Neuropharmacology 52 (3): 744–54. doi:10.1016/j.neuropharm.2006.09.018. PMID 17095021. 
  21. ^ D.E. Golan, A.H Tashjian Jr, E.J. Armstrong, A.W. Armstrong. (2007) Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy Lippincott Williams & Wilkins ISBN 0781783550
  22. ^ Lipton SA (2004). "Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults". NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 1 (1): 101–10. PMID 15717010. 
  23. ^ Parsons CG, Stöffler A, Danysz W (2007). "Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse". Neuropharmacology 53 (6): 699–723. doi:10.1016/j.neuropharm.2007.07.013. PMID 17904591. 
  24. ^ Principles and Practice of Pharmacology for Anaesthetists By Norton Elwy Williams, Thomas Norman Calvey Published 2001 Blackwell Publishing ISBN 0632056053
  25. ^ Patil PN (2002). "Everhardus J. Ariëns (1918–2002): a tribute". Trends Pharmacol. Sci. 23 (7): 344-5. doi:10.1016/S0165-6147(02)02068-0. 
  26. ^ Bosier B, Hermans E (2007). "Versatility of GPCR recognition by drugs: from biological implications to therapeutic relevance". Trends Pharmacol. Sci. 28 (8): 438–46. doi:10.1016/j.tips.2007.06.001. PMID 17629964. 
  27. ^ Pulvirenti L, Koob GF (2002). "Being partial to psychostimulant addiction therapy". Trends Pharmacol. Sci. 23 (4): 151–3. PMID 11931978. 
  28. ^ Vadivelu N, Hines RL (2007). "Buprenorphine: a unique opioid with broad clinical applications". J Opioid Manag 3 (1): 49–58. PMID 17367094. 
  29. ^ Greasley PJ, Clapham JC (2006). "Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing?". Eur. J. Pharmacol. 553 (1-3): 1–9. doi:10.1016/j.ejphar.2006.09.032. PMID 17081515. 
  30. ^ Kenakin T (2004). "Efficacy as a vector: the relative prevalence and paucity of inverse agonism". Mol. Pharmacol. 65 (1): 2–11. doi:10.1124/mol.65.1.2. PMID 14722230. 
  31. ^ Leurs R, Church MK, Taglialatela M (2002). "H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects". Clin Exp Allergy 32 (4): 489-98. PMID 11972592. 
  32. ^ Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamäki A (2001). "Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors". J. Biol. Chem. 276 (33): 31279–84. doi:10.1074/jbc.M104167200. PMID 11395517. 

  Results from FactBites:
 
Receptor Workbook (4044 words)
An antagonist that binds to the receptor in a reversible mass-action manner is referred to as a competitive antagonist.
The dose-response curve obtained in the presence of a competitive antagonist is parallel to the dose-response curve obtained in the absence of antagonist.
In the resting state the receptor is not occupied by an agonist and the G-protein exists as trimer of the alpha, beta and gamma subunits with GDP bound to the alpha subunit.
CNSforum | Anxiety - Serotonergic receptor systems (1189 words)
The 5-HT3 receptor is structurally similar to the nicotinic acetylcholine receptor and is composed of 5 subunits.
The 5-HT1A receptor is coupled to inhibitory G-proteins, which dissociate from the receptor on agonist binding, and inhibit secondary messenger signaling mechanisms.
The 5-HT2 receptor is coupled to stimulatory G-proteins, which dissociate from the receptor on agonist binding, and initiate secondary messenger signaling mechanisms.
  More results at FactBites »


 

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