Antagonists: Difference between revisions
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<StructureSection load='4dkl' size='400' side='right' caption='Crystal structure of the mu-opioid receptor bound to a morphinan antagonist, cholesterol, PEG 400, sulfate, mono-oleoyl-glycerol and Cl- ion (PDB entry [[4dkl]])' scene=4dkl/Overall_structure/1''> | <StructureSection load='4dkl' size='400' side='right' caption='Crystal structure of the mu-opioid receptor bound to a morphinan antagonist, cholesterol, PEG 400, sulfate, mono-oleoyl-glycerol and Cl- ion (PDB entry [[4dkl]])' scene=4dkl/Overall_structure/1''> | ||
'''Under construction''' | '''Under construction''' | ||
Ligands that bind to a receptor but fail to activate the physiological response are receptor '''antagonists'''. | |||
'''Competitive antagonists''' bind to receptors at the same binding site (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. Naloxone (also known as Narcan) is used to reverse opioid overdose caused by drugs such as heroin or morphine ([[μ Opioid Receptors]]). | |||
*[[Mu Opioid Receptor Bound to a Morphinan Antagonist]] | *[[Mu Opioid Receptor Bound to a Morphinan Antagonist]] | ||
*<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Lbd_domain/4'>The ligand-binding domain (LBD)</scene> participates directly in agonist/competitive antagonist binding, affects activation gating, and is the portion that forms the 'middle' layer. | |||
::<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Lbd_zk1/2'>The competitive antagonist ZK200775 is bound to the LBD</scene> in the structure of [[Glutamate receptor (GluA2)]]. | |||
::The small molecule <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Zk1_zoom/1'>ZK200775, a phosphonate quinoxalinedione AMPA antagonist</scene><ref>PMID: 9724812</ref>, was studied as a treatment for stroke because it had demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers; however, in a multicenter, double-blind, randomized, placebo-controlled phase II trial, it was found to have significant sedative effects in patients with acute stroke which precludes its further development as a neuroprotective agent<ref>PMID: 16131799</ref>. | |||
'''Physiological antagonists''', substances that 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 alpha-[[adrenergic receptor]] activation. | |||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 16:49, 12 October 2021
Under construction Ligands that bind to a receptor but fail to activate the physiological response are receptor antagonists. Competitive antagonists bind to receptors at the same binding site (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. Naloxone (also known as Narcan) is used to reverse opioid overdose caused by drugs such as heroin or morphine (μ Opioid Receptors).
Physiological antagonists, substances that 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 alpha-adrenergic receptor activation.
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ReferencesReferences
- ↑ Turski L, Huth A, Sheardown M, McDonald F, Neuhaus R, Schneider HH, Dirnagl U, Wiegand F, Jacobsen P, Ottow E. ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10960-5. PMID:9724812
- ↑ Walters MR, Kaste M, Lees KR, Diener HC, Hommel M, De Keyser J, Steiner H, Versavel M. The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: a double-blind, multicentre, placebo-controlled safety and tolerability study. Cerebrovasc Dis. 2005;20(5):304-9. Epub 2005 Aug 30. PMID:16131799 doi:10.1159/000087929