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<title>Functional selectivity</title>

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<span id="openzim-page-title" class="mw-page-title-main"><span class="mw-page-title-main">Functional selectivity</span></span>

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</style><div role="note" class="hatnote navigation-not-searchable">Not to be confused with <a href="Binding_selectivity" title="Binding selectivity">binding selectivity</a>.</div>

<p><b>Functional selectivity</b> (or <b>agonist trafficking</b>, <b>biased agonism</b>, <b>biased signaling</b>, <b>ligand bias</b>, and <b>differential engagement</b>) is the <a href="Ligand_(biochemistry)" title="Ligand (biochemistry)">ligand</a>-dependent selectivity for certain <a href="Signal_transduction" title="Signal transduction">signal transduction</a> pathways relative to a reference ligand (often the endogenous hormone or peptide) at the same <a href="Receptor_(biochemistry)" title="Receptor (biochemistry)">receptor</a>.<sup id="cite_ref-:0_1-0" class="reference"><a href="#cite_note-:0-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Functional selectivity can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor.<sup id="cite_ref-pmid15994454_2-0" class="reference"><a href="#cite_note-pmid15994454-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> Functional selectivity, or biased signaling, is most extensively characterized at <a href="G_protein_coupled_receptors" class="mw-redirect" title="G protein coupled receptors">G protein coupled receptors</a> (GPCRs).<sup id="cite_ref-BockMerten2012_3-0" class="reference"><a href="#cite_note-BockMerten2012-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics<sup id="cite_ref-MateraFlammini2014_4-0" class="reference"><a href="#cite_note-MateraFlammini2014-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> or antiproliferative drugs,<sup id="cite_ref-CristofaroSpinello2018_5-0" class="reference"><a href="#cite_note-CristofaroSpinello2018-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> or those at opioid receptors that mediate pain, show potential at various receptor families to increase beneficial properties while reducing side effects. For example, pre-clinical studies with <a href="G_protein" title="G protein">G protein</a> biased agonists at the <a href="%CE%9C-opioid_receptor" title="Μ-opioid receptor">μ-opioid receptor</a> show equivalent efficacy for treating pain with reduced risk for addictive potential and <a href="Respiratory_depression" class="mw-redirect" title="Respiratory depression">respiratory depression</a>.<sup id="cite_ref-:0_1-1" class="reference"><a href="#cite_note-:0-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant. For example, a beta-arrestin biased agonist of the chemokine receptor <a href="CXCR3" title="CXCR3">CXCR3</a> induced greater <a href="Chemotaxis" title="Chemotaxis">chemotaxis</a> of T cells relative to a G protein biased agonist.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup>

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<div class="mw-heading mw-heading2"><h2 id="Functional_vs._traditional_selectivity">Functional vs. traditional selectivity</h2></div>

<p>Functional selectivity has been proposed to broaden conventional definitions of <a href="Pharmacology" title="Pharmacology">pharmacology</a>.

</p><p><b>Traditional pharmacology</b> <a href="Postulate" class="mw-redirect" title="Postulate">posits</a> that a <a href="Ligand_(biochemistry)" title="Ligand (biochemistry)">ligand</a> can be either classified as an <a href="Agonist" title="Agonist">agonist</a> (full or partial), <a href="Receptor_antagonist" title="Receptor antagonist">antagonist</a> or more recently an <a href="Inverse_agonist" title="Inverse agonist">inverse agonist</a> through a specific receptor subtype, and that this characteristic will be consistent with all <a href="Effector_(biology)" title="Effector (biology)">effector</a> (<a href="Second_messenger_system" title="Second messenger system">second messenger</a>) systems coupled to that receptor. While this dogma has been the backbone of ligand-receptor interactions for decades now, more recent data indicates that this classic definition of ligand-protein associations does not hold true for a number of compounds; such compounds may be termed as <a href="Mixed_agonist-antagonist" class="mw-redirect" title="Mixed agonist-antagonist">mixed agonist-antagonists</a>.

</p><p><b>Functional selectivity</b> posits that a ligand may inherently produce a mix of the classic characteristics through a single receptor isoform depending on the effector pathway coupled to that receptor. For instance, a ligand can not easily be classified as an agonist or antagonist, because it can be a little of both, depending on its preferred signal transduction pathways. Thus, such ligands must instead be classified on the basis of their individual effects in the cell, instead of being either an agonist or antagonist to a receptor.

</p><p>These observations were made in a number of different <a href="Gene_expression#Expression_system" title="Gene expression">expression systems</a>, and therefore functional selectivity is not just an <a href="Epiphenomenon" title="Epiphenomenon">epiphenomenon</a> of one particular expression system.

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<div class="mw-heading mw-heading2"><h2 id="Examples">Examples</h2></div>

<p>One notable example of functional selectivity occurs with the <a href="5-HT2A_receptor" title="5-HT2A receptor">5-HT<sub>2A</sub> receptor</a>, as well as the <a href="5-HT2C_receptor" title="5-HT2C receptor">5-HT<sub>2C</sub> receptor</a>. <a href="Serotonin" title="Serotonin">Serotonin</a>, the main endogenous ligand of <a href="5-HT_receptor" title="5-HT receptor">5-HT receptors</a>, is a functionally selective agonist at this receptor, activating <a href="Phospholipase_C" title="Phospholipase C">phospholipase C</a> (which leads to <a href="Inositol_triphosphate" class="mw-redirect" title="Inositol triphosphate">inositol triphosphate</a> accumulation), but does not activate <a href="Phospholipase_A2" title="Phospholipase A2">phospholipase A2</a>, which would result in <a href="Arachidonic_acid" title="Arachidonic acid">arachidonic acid</a> signaling. However, the other endogenous compound <a href="Dimethyltryptamine" title="Dimethyltryptamine">dimethyltryptamine</a> activates arachidonic acid signaling at the 5-HT<sub>2A</sub> receptor, as do many exogenous hallucinogens such as <a href="2%2C5-Dimethoxy-4-bromoamphetamine" title="2,5-Dimethoxy-4-bromoamphetamine">DOB</a> and <a href="Lysergic_acid_diethylamide" class="mw-redirect" title="Lysergic acid diethylamide">lysergic acid diethylamide</a> (LSD). Notably, LSD does not activate IP<sub>3</sub> signaling through this receptor to any significant extent. (Conversely, LSD, unlike serotonin, has negligible affinity for the 5-HT<sub>2C-VGV</sub> isoform, is unable to promote calcium release, and is, thus, functionally selective at 5-HT<sub>2C</sub>.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup>) Oligomers, specifically 5-HT<sub>2A</sub>–<a href="Metabotropic_glutamate_receptor_2" title="Metabotropic glutamate receptor 2"><abbr title="metabotropic glutamate receptor 2">mGluR2</abbr></a><span class="sr-only" style="border: 0; clip: rect(0, 0, 0, 0); clip-path: polygon(0px 0px, 0px 0px, 0px 0px); height: 1px; margin: -1px; overflow: hidden; padding: 0; position: absolute; width: 1px; white-space: nowrap;">Tooltip metabotropic glutamate receptor 2</span> <a href="Heteromer" title="Heteromer">heteromers</a>, mediate this effect. This may explain why some direct 5-HT<sub>2</sub> receptor agonists have <a href="Psychedelic_drug" title="Psychedelic drug">psychedelic</a> effects, whereas compounds that indirectly increase serotonin signaling at the 5-HT<sub>2</sub> receptors generally do not, for example: <a href="Selective_serotonin_reuptake_inhibitor" title="Selective serotonin reuptake inhibitor">selective serotonin reuptake inhibitors</a> (SSRIs), <a href="Monoamine_oxidase_inhibitor" title="Monoamine oxidase inhibitor">monoamine oxidase inhibitors</a> (MAOIs), and medications using 5HT<sub>2A</sub> receptor agonists that do not have constitutive activity at the mGluR2 <a href="Protein_dimer" title="Protein dimer">dimer</a>, such as <a href="Lisuride" title="Lisuride">lisuride</a>.<sup id="cite_ref-pmid16803859_9-0" class="reference"><a href="#cite_note-pmid16803859-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup>

</p><p><a href="Tianeptine" title="Tianeptine">Tianeptine</a>, an <a href="Atypical_antidepressant" title="Atypical antidepressant">atypical antidepressant</a>, is thought to exhibit functional selectivity at the <a href="%CE%9C-opioid_receptor" title="Μ-opioid receptor">μ-opioid receptor</a> to mediate its antidepressant effects.<sup id="cite_ref-pmid28303899_10-0" class="reference"><a href="#cite_note-pmid28303899-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid26068549_11-0" class="reference"><a href="#cite_note-pmid26068549-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup>

</p><p><a href="Oliceridine" title="Oliceridine">Oliceridine</a> is a μ-opioid receptor agonist that has been described to be functionally selective towards G protein and away from β-arrestin2 pathways.<sup id="cite_ref-pmid23300227_12-0" class="reference"><a href="#cite_note-pmid23300227-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> However, recent reports highlight that, rather than functional selectivity or 'G protein bias', this agonist has low intrinsic efficacy.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> <i>In vivo</i>, it has been reported to mediate pain relief without tolerance nor gastrointestinal side effects.

</p><p>The <a href="Delta_opioid_receptor" class="mw-redirect" title="Delta opioid receptor">delta opioid receptor</a> agonists <a href="SNC80" class="mw-redirect" title="SNC80">SNC80</a> and <a href="ARM390" title="ARM390">ARM390</a> demonstrate functional selectivity that is thought to be due to their differing capacity to cause <a href="Receptor_internalization" class="mw-redirect" title="Receptor internalization">receptor internalization</a>.<sup id="cite_ref-Pradhan_AA_et_al_2011_14-0" class="reference"><a href="#cite_note-Pradhan_AA_et_al_2011-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> While SNC80 causes delta opioid receptors to internalize, ARM390 causes very little receptor internalization.<sup id="cite_ref-Pradhan_AA_et_al_2011_14-1" class="reference"><a href="#cite_note-Pradhan_AA_et_al_2011-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Functionally, that means that the effects of SNC80 (e.g. <a href="Analgesia" class="mw-redirect" title="Analgesia">analgesia</a>) do not occur when a subsequent dose follows the first, whereas the effects of ARM390 persist.<sup id="cite_ref-Pradhan_AA_et_al_2011_14-2" class="reference"><a href="#cite_note-Pradhan_AA_et_al_2011-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> However, tolerance to ARM390's analgesia still occurs eventually after multiple doses, though through a mechanism that does not involve receptor internalization.<sup id="cite_ref-Pradhan_AA_et_al_2011_14-3" class="reference"><a href="#cite_note-Pradhan_AA_et_al_2011-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Interestingly, the other effects of ARM390 (e.g. decreased anxiety) persist after tolerance to its analgesic effects has occurred.<sup id="cite_ref-Pradhan_AA_et_al_2011_14-4" class="reference"><a href="#cite_note-Pradhan_AA_et_al_2011-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup>

</p><p>An example of functional selectivity to bias metabolism was demonstrated for an electron transfer protein <a href="Cytochrome_P450_reductase" title="Cytochrome P450 reductase">cytochrome P450 reductase</a> (POR) with binding of small molecule ligands shown to alter the protein conformation and interaction with various redox partner proteins of POR.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup>

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<ul><li><a href="Signal_transduction" title="Signal transduction">Signal transduction</a></li>

<li><a href="Second_messenger_system" title="Second messenger system">Second messenger system</a></li></ul>

<div class="mw-heading mw-heading2"><h2 id="References">References</h2></div>

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</ol></div></div>

<div class="mw-heading mw-heading2"><h2 id="Further_reading">Further reading</h2></div>

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<li><cite id="CITEREFGesty-PalmerLuttrell2011" class="citation book cs1">Gesty-Palmer D, Luttrell LM (2011). "Refining Efficacy: Exploiting Functional Selectivity for Drug Discovery". <i>Pharmacology of G Protein Coupled Receptors</i>. Advances in Pharmacology. Vol. 62. pp. <span class="nowrap">79–</span>107. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FB978-0-12-385952-5.00009-9">10.1016/B978-0-12-385952-5.00009-9</a>. <a href="ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <bdi>9780123859525</bdi>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21907907">21907907</a>.</cite></li>

<li><cite id="CITEREFDeWireViolin2011" class="citation journal cs1">DeWire SM, Violin JD (July 2011). <a rel="nofollow" class="external text" href="https://doi.org/10.1161%2FCIRCRESAHA.110.231308">"Biased ligands for better cardiovascular drugs: dissecting G-protein-coupled receptor pharmacology"</a>. <i>Circ. Res</i>. <b>109</b> (2): <span class="nowrap">205–</span>16. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1161%2FCIRCRESAHA.110.231308">10.1161/CIRCRESAHA.110.231308</a></span>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21737816">21737816</a>.</cite></li>

<li><cite id="CITEREFKenakin_T1995" class="citation journal cs1">Kenakin T (1995). <span class="id-lock-subscription" title="Paid subscription required"><a rel="nofollow" class="external text" href="https://cdr.lib.unc.edu/record/uuid:e3546176-4b38-4c42-bfec-8990d429363f">"Agonist-Receptor Efficacy. II. Agonist Trafficking of Receptor Signals"</a></span>. <i>Trends Pharmacol Sci</i>. <b>16</b> (7): <span class="nowrap">232–</span>8. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0165-6147%2800%2989032-X">10.1016/S0165-6147(00)89032-X</a>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/7667897">7667897</a>.</cite></li></ul>

</div>

<p><br>

</p>

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</style><div id="Pharmacology105" style="font-size:114%;margin:0 4em"><a href="Pharmacology" title="Pharmacology">Pharmacology</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Ligand_(biochemistry)" title="Ligand (biochemistry)">Ligand (biochemistry)</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Excitatory10" scope="row" class="navbox-group" style="width:1%;text-align: center;">Excitatory</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Agonist" title="Agonist">Agonist</a></li>

<li><a href="Endogenous_agonist" title="Endogenous agonist">Endogenous agonist</a></li>

<li><a href="Irreversible_agonist" title="Irreversible agonist">Irreversible agonist</a></li>

<li><a href="Partial_agonist" title="Partial agonist">Partial agonist</a></li>

<li><a href="Superagonist" title="Superagonist">Superagonist</a></li>

<li><a href="Physiological_agonism_and_antagonism" title="Physiological agonism and antagonism">Physiological agonist</a></li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Inhibitory10" scope="row" class="navbox-group" style="width:1%;text-align: center;">Inhibitory</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Receptor_antagonist" title="Receptor antagonist">Antagonist</a></li>

<li><a href="Competitive_antagonist" class="mw-redirect" title="Competitive antagonist">Competitive antagonist</a></li>

<li><a href="Irreversible_antagonist" title="Irreversible antagonist">Irreversible antagonist</a></li>

<li><a href="Physiological_agonism_and_antagonism" title="Physiological agonism and antagonism">Physiological antagonist</a></li>

<li><a href="Inverse_agonist" title="Inverse agonist">Inverse agonist</a></li>

<li><a href="Enzyme_inhibitor" title="Enzyme inhibitor">Enzyme inhibitor</a></li></ul>

</div></td></tr></tbody></table><div>

<li><a href="Neurotransmitter" title="Neurotransmitter">Neurotransmitter</a></li>

<li><a href="Agonist-antagonist" title="Agonist-antagonist">Agonist-antagonist</a></li>

<li><a href="Pharmacophore" title="Pharmacophore">Pharmacophore</a></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Pharmacodynamics" title="Pharmacodynamics">Pharmacodynamics</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Activity_at_receptor20" scope="row" class="navbox-group" style="width:1%;text-align: center;">Activity at receptor</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<li><a href="Mechanism_of_action" title="Mechanism of action">Mechanism of action</a></li>

<li><a href="Mode_of_action" title="Mode of action">Mode of action</a></li>

<li><a href="Molecular_binding" title="Molecular binding">Binding</a></li>

<li><a href="Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptor (biochemistry)</a></li>

<li><a href="Desensitization_(medicine)" title="Desensitization (medicine)">Desensitization (medicine)</a></li>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Other_effects_of_ligand23" scope="row" class="navbox-group" style="width:1%;text-align: center;">Other effects of ligand</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li>Selectivity (<a href="Binding_selectivity" title="Binding selectivity">Binding</a>, )</li>

<li><a href="Pleiotropy_(drugs)" class="mw-redirect" title="Pleiotropy (drugs)">Pleiotropy (drugs)</a></li>

<li><a href="Non-specific_effect_of_vaccines" title="Non-specific effect of vaccines">Non-specific effect of vaccines</a></li>

<li><a href="Adverse_effect" title="Adverse effect">Adverse effect</a></li>

<li><a href="Toxicity" title="Toxicity">Toxicity</a> (<a href="Neurotoxicity" title="Neurotoxicity">Neurotoxicity</a>)</li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Analysis8" scope="row" class="navbox-group" style="width:1%;text-align: center;">Analysis</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Dose%E2%80%93response_relationship" title="Dose–response relationship">Dose–response relationship</a></li>

<li><a href="Hill_equation_(biochemistry)" title="Hill equation (biochemistry)">Hill equation (biochemistry)</a></li>

<li><a href="Schild_plot" class="mw-redirect" title="Schild plot">Schild plot</a></li>

<li><a href="Del_Castillo_Katz_model" class="mw-redirect" title="Del Castillo Katz model">Del Castillo Katz model</a></li>

<li><a href="Cheng-Prussoff_Equation" class="mw-redirect" title="Cheng-Prussoff Equation">Cheng-Prussoff Equation</a></li>

<li>Methods (<a href="Organ_bath" title="Organ bath">Organ bath</a>, <a href="Ligand_binding_assay" title="Ligand binding assay">Ligand binding assay</a>, <a href="Patch_clamp" title="Patch clamp">Patch clamp</a>)</li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Metrics7" scope="row" class="navbox-group" style="width:1%;text-align: center;">Metrics</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Efficacy#Pharmacology" title="Efficacy">Efficacy</a></li>

<li><a href="Intrinsic_activity" title="Intrinsic activity">Intrinsic activity</a></li>

<li><a href="Potency_(pharmacology)" title="Potency (pharmacology)">Potency</a> (<a href="EC50" title="EC50">EC50</a>, <a href="IC50" title="IC50">IC50</a>, <a href="Effective_dose_(pharmacology)" title="Effective dose (pharmacology)">ED50</a>, <a href="Median_lethal_dose" title="Median lethal dose">LD50</a>, <a href="Median_toxic_dose" title="Median toxic dose">TD50</a>)</li>

<li><a href="Therapeutic_index" title="Therapeutic index">Therapeutic index</a></li>

<li><a href="Dissociation_constant#Protein-ligand_binding" title="Dissociation constant">Affinity</a></li></ul>

</div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Pharmacokinetics" title="Pharmacokinetics">Pharmacokinetics</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Metrics7" scope="row" class="navbox-group" style="width:1%;text-align: center;">Metrics</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Loading_dose" title="Loading dose">Loading dose</a></li>

<li><a href="Volume_of_distribution" title="Volume of distribution">Volume of distribution</a> (<a href="Initial_volume_of_distribution" title="Initial volume of distribution">Initial</a>)</li>

<li><a href="Rate_of_infusion" title="Rate of infusion">Rate of infusion</a></li>

<li><a href="Onset_of_action" title="Onset of action">Onset of action</a></li>

<li><a href="Biological_half-life" title="Biological half-life">Biological half-life</a></li>

<li><a href="Plasma_protein_binding" title="Plasma protein binding">Plasma protein binding</a></li>

<li><a href="Bioavailability" title="Bioavailability">Bioavailability</a></li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="LADME5" scope="row" class="navbox-group" style="width:1%;text-align: center;">LADME</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="ADME" title="ADME">(L)ADME</a>: (<a href="Liberation_(pharmacology)" title="Liberation (pharmacology)">Liberation</a>)</li>

<li><a href="Absorption_(pharmacology)" title="Absorption (pharmacology)">Absorption</a></li>

<li><a href="Distribution_(pharmacology)" title="Distribution (pharmacology)">Distribution</a></li>

<li><a href="Drug_metabolism" title="Drug metabolism">Metabolism</a></li>

<li><a href="Excretion" title="Excretion">Excretion</a> (<a href="Clearance_(pharmacology)" title="Clearance (pharmacology)">Clearance</a>)</li></ul>

</div></td></tr></tbody></table><div>

<ul><li><a href="Compartment_(pharmacokinetics)" title="Compartment (pharmacokinetics)">Compartment</a></li>

<li><a href="Bioequivalence" title="Bioequivalence">Bioequivalence</a></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align: center;">Related<br> fields</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Neuroscience_and_psychology35" scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Neuroscience" title="Neuroscience">Neuroscience</a> and <a href="Psychology" title="Psychology">psychology</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<li><a href="Neuropsychopharmacology" title="Neuropsychopharmacology">Neuropsychopharmacology</a></li>

<li><a href="Neuropharmacology" title="Neuropharmacology">Neuropharmacology</a></li>

<li><a href="Psychopharmacology" title="Psychopharmacology">Psychopharmacology</a></li>

<li><a href="Electrophysiology" title="Electrophysiology">Electrophysiology</a></li>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Medicine12" scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Medicine" title="Medicine">Medicine</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Clinical_pharmacology" title="Clinical pharmacology">Clinical pharmacology</a></li>

<li><a href="Pharmacy" title="Pharmacy">Pharmacy</a></li>

<li><a href="Medicinal_chemistry" title="Medicinal chemistry">Medicinal chemistry</a></li>

<li><a href="Pharmacoepidemiology" title="Pharmacoepidemiology">Pharmacoepidemiology</a></li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Biochemistry_and_genetics33" scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Biochemistry" title="Biochemistry">Biochemistry</a> and <a href="Genetics" title="Genetics">genetics</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Pharmacoinformatics" title="Pharmacoinformatics">Pharmacoinformatics</a></li>

<li><a href="Pharmacogenetics" class="mw-redirect" title="Pharmacogenetics">Pharmacogenetics</a></li>

<li><a href="Pharmacogenomics" title="Pharmacogenomics">Pharmacogenomics</a></li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Toxicology14" scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Toxicology" title="Toxicology">Toxicology</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Pharmacotoxicology" title="Pharmacotoxicology">Pharmacotoxicology</a></li>

<li><a href="Neurotoxicology" class="mw-redirect" title="Neurotoxicology">Neurotoxicology</a></li></ul>

</div></td></tr></tbody></table><div>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Drug_discovery18" scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="Drug_discovery" title="Drug discovery">Drug discovery</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Classical_pharmacology" title="Classical pharmacology">Classical pharmacology</a></li>

<li><a href="Reverse_pharmacology" title="Reverse pharmacology">Reverse pharmacology</a></li></ul>

</div></td></tr></tbody></table><div>

<ul><li><a href="Photopharmacology" title="Photopharmacology">Photopharmacology</a></li>

<li><a href="Immunopharmacology" class="mw-redirect" title="Immunopharmacology">Immunopharmacology</a></li>

<li><a href="Cell_biology" title="Cell biology">Cell biology</a></li>

<li><a href="Physiology" title="Physiology">Physiology</a></li></ul></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align: center;">Other</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<li><a href="Coinduction_(anesthetics)" title="Coinduction (anesthetics)">Coinduction (anesthetics)</a></li>

<li><a href="Combination_therapy" title="Combination therapy">Combination therapy</a></li>

<li><a href="Functional_analog_(chemistry)" title="Functional analog (chemistry)">Functional analog (chemistry)</a></li>

<li><a href="Polypharmacology" title="Polypharmacology">Polypharmacology</a></li>

<li><a href="Chemotherapy" title="Chemotherapy">Chemotherapy</a></li>

<li><a href="Lists_of_drugs" title="Lists of drugs">Lists of drugs</a></li>

<li><a href="WHO_list_of_essential_medicines" class="mw-redirect" title="WHO list of essential medicines">WHO list of essential medicines</a></li>

</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Tolerance_and_resistance24" scope="row" class="navbox-group" style="width:1%;text-align: center;">Tolerance and resistance</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Drug_tolerance" title="Drug tolerance">Drug tolerance</a></li>

<li><a href="Tachyphylaxis" title="Tachyphylaxis">Tachyphylaxis</a></li>

<li><a href="Drug_resistance" title="Drug resistance">Drug resistance</a></li>

<li><a href="Antibiotic_resistance" class="mw-redirect" title="Antibiotic resistance">Antibiotic resistance</a></li>

<li><a href="Multiple_drug_resistance" title="Multiple drug resistance">Multiple drug resistance</a></li></ul>

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</div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Antimicrobial_pharmacology26" scope="row" class="navbox-group" style="width:1%;text-align: center;">Antimicrobial pharmacology</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Antimicrobial_pharmacodynamics" title="Antimicrobial pharmacodynamics">Antimicrobial pharmacodynamics</a></li>

<li><a href="Minimum_inhibitory_concentration" title="Minimum inhibitory concentration">Minimum inhibitory concentration</a></li>

<li><a href="Bacteriostatic_agent" title="Bacteriostatic agent">Bacteriostatic</a></li>

<li><a href="Minimum_bactericidal_concentration" title="Minimum bactericidal concentration">Minimum bactericidal concentration</a></li>

<li><a href="Bactericide" title="Bactericide">Bactericide</a></li></ul>

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