<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1134-8046</journal-id>
<journal-title><![CDATA[Revista de la Sociedad Española del Dolor]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. Soc. Esp. Dolor]]></abbrev-journal-title>
<issn>1134-8046</issn>
<publisher>
<publisher-name><![CDATA[Inspira Network Group, S.L ]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1134-80462021000600008</article-id>
<article-id pub-id-type="doi">10.20986/resed.2021.3891/2021</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Nuevos opioides con diferente mecanismo de acción intracelular; ¿una nueva ventana terapéutica se abre ante nosotros?]]></article-title>
<article-title xml:lang="en"><![CDATA[New opioids with different intracellular mechanism of action; is a new therapeutic window opening up?]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Mugabure Bujedo]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[González Santos]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Hospital Universitario de Donostia Departamento de Anestesiología, Cuidados Críticos y Medicina del Dolor ]]></institution>
<addr-line><![CDATA[San Sebastián ]]></addr-line>
<country>España</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Hospital Universitario de Donostia Unidad del dolor, Manejo del dolor agudo y crónico ]]></institution>
<addr-line><![CDATA[San Sebastián ]]></addr-line>
<country>España</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>10</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>10</month>
<year>2021</year>
</pub-date>
<volume>28</volume>
<numero>5</numero>
<fpage>292</fpage>
<lpage>297</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_arttext&amp;pid=S1134-80462021000600008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_abstract&amp;pid=S1134-80462021000600008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_pdf&amp;pid=S1134-80462021000600008&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN Los opioides son los fármacos más utilizados para el tratamiento del dolor agudo. Los opioides convencionales se utilizan ampliamente para el tratamiento del dolor agudo en el entorno postoperatorio. Sin embargo, una de las principales preocupaciones de dichos opioides es su ventana terapéutica, es decir, el intervalo entre las dosis que producen el efecto terapéutico deseado (analgesia) y las dosis que producen efectos adversos relacionados con los opioides (EARO) no deseados. Los opioides convencionales sobre receptores &#956; tienen una ventana terapéutica estrecha, en parte debido a su mecanismo de acción (MdA): se unen a los receptores &#956; y activan de forma no selectiva 2 vías de señalización intracelular, lo que provoca analgesia y EARO. Esta revisión explora el potencial clínico de los ligandos de los receptores &#956; con señalización diferencial. Los agentes con un MdA de "señalización diferencial" representan un enfoque innovador que puede mejorar la ventana terapéutica. Estos agentes modulan la actividad de los receptores &#956; para activar selectivamente las vías de señalización asociadas a la analgesia, al tiempo que limitan la actividad en las vías de señalización posteriores que conducen a los EARO. Por todo ello, la señalización diferencial puede satisfacer una necesidad no cubierta en el tratamiento del dolor postoperatorio. Oliceridina es un claro exponente de esta nueva generación.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT Opioids are the most drugs used for the management of acute pain. Conventional opioids are widely used for acute pain management in the postoperative setting. However, a primary concern with conventional opioids is their therapeutic window, the range between doses that produce the desired therapeutic effect (analgesia) and doses that produce unwanted opioid-related adverse events (ORAEs). Conventional &#956; receptor opioids have a narrow therapeutic window in part because of their mechanism of action (MoA): they bind to &#956; receptors and non-selectively activate two intracellular signaling pathways, leading to analgesia and to ORAEs. This review explores the clinical potential of &#956; receptor ligands with differential signaling. Agents with a 'differential signaling" MoA represent an innovative approach that may enhance the therapeutic window. These agents modulate &#956; receptor activity to selectively engage downstream signaling pathways associated with analgesia while limiting activity in downstream signaling pathways that lead to ORAEs. Meanwhile, differential signaling may fulfill an unmet need in the management of postoperative pain. Oliceridine is a clear exponent of this new opioid generation.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Opioides]]></kwd>
<kwd lng="es"><![CDATA[mecanismo de acción]]></kwd>
<kwd lng="es"><![CDATA[señalización diferencial]]></kwd>
<kwd lng="es"><![CDATA[oliceridina]]></kwd>
<kwd lng="en"><![CDATA[Opioids]]></kwd>
<kwd lng="en"><![CDATA[mechanism of action]]></kwd>
<kwd lng="en"><![CDATA[differential signaling]]></kwd>
<kwd lng="en"><![CDATA[oliceridine]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Chou]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Gordon]]></surname>
<given-names><![CDATA[DB]]></given-names>
</name>
<name>
<surname><![CDATA[de Leon-Casasola]]></surname>
<given-names><![CDATA[OA]]></given-names>
</name>
<name>
<surname><![CDATA[Rosenberg]]></surname>
<given-names><![CDATA[JM]]></given-names>
</name>
<name>
<surname><![CDATA[Bickler]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Brennan]]></surname>
<given-names><![CDATA[T]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and pain medicine, and the American Society of Anesthesiologists' committee on regional anesthesia, executive committee, and administrative council]]></article-title>
<source><![CDATA[J Pain]]></source>
<year>2016</year>
<volume>17</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>131-57</page-range></nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Benyamin]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Trescot]]></surname>
<given-names><![CDATA[AM]]></given-names>
</name>
<name>
<surname><![CDATA[Datta]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Buenaventura]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Adlaka]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Sehgal]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Opioid complications and side effects]]></article-title>
<source><![CDATA[Pain Physician]]></source>
<year>2008</year>
<volume>11</volume>
<numero>2 Suppl</numero>
<issue>2 Suppl</issue>
<page-range>S105-20</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Cashman]]></surname>
<given-names><![CDATA[JN]]></given-names>
</name>
<name>
<surname><![CDATA[Dolin]]></surname>
<given-names><![CDATA[SJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Respiratory and haemodynamic effects of acute postoperative pain management: evidence from published data]]></article-title>
<source><![CDATA[Br J Anaesth]]></source>
<year>2004</year>
<volume>93</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>212-23</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Gan]]></surname>
<given-names><![CDATA[TJ]]></given-names>
</name>
<name>
<surname><![CDATA[Diemunsch]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Habib]]></surname>
<given-names><![CDATA[AS]]></given-names>
</name>
<name>
<surname><![CDATA[Kovac]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Kranke]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
<name>
<surname><![CDATA[Meyer]]></surname>
<given-names><![CDATA[TA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Consensus guidelines for the management of postoperative nausea and vomiting]]></article-title>
<source><![CDATA[Anesth Analg]]></source>
<year>2014</year>
<volume>118</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>85-113</page-range></nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Hagle]]></surname>
<given-names><![CDATA[ME]]></given-names>
</name>
<name>
<surname><![CDATA[Lehr]]></surname>
<given-names><![CDATA[VT]]></given-names>
</name>
<name>
<surname><![CDATA[Brubakken]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Shipee]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Respiratory depression in adult patients with intravenous patient-controlled analgesia]]></article-title>
<source><![CDATA[Orthop Nurs]]></source>
<year>2004</year>
<volume>23</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>18-27</page-range></nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Wheeler]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Oderda]]></surname>
<given-names><![CDATA[GM]]></given-names>
</name>
<name>
<surname><![CDATA[Ashburn]]></surname>
<given-names><![CDATA[MA]]></given-names>
</name>
<name>
<surname><![CDATA[Lipman]]></surname>
<given-names><![CDATA[AG]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Adverse events associated with postoperative opioid analgesia: a systematic review]]></article-title>
<source><![CDATA[J Pain]]></source>
<year>2002</year>
<volume>3</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>159-80</page-range></nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Kessler]]></surname>
<given-names><![CDATA[ER]]></given-names>
</name>
<name>
<surname><![CDATA[Shah]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Gruschkus]]></surname>
<given-names><![CDATA[SK]]></given-names>
</name>
<name>
<surname><![CDATA[Raju]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes]]></article-title>
<source><![CDATA[Pharmacotherapy]]></source>
<year>2013</year>
<volume>33</volume>
<numero>4</numero>
<issue>4</issue>
<page-range>383-91</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Oderda]]></surname>
<given-names><![CDATA[GM]]></given-names>
</name>
<name>
<surname><![CDATA[Gan]]></surname>
<given-names><![CDATA[TJ]]></given-names>
</name>
<name>
<surname><![CDATA[Johnson]]></surname>
<given-names><![CDATA[BH]]></given-names>
</name>
<name>
<surname><![CDATA[Robinson]]></surname>
<given-names><![CDATA[SB]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Effect of opioid-related adverse events on outcomes in selected surgical patients]]></article-title>
<source><![CDATA[J Pain Palliat Care Pharmacother]]></source>
<year>2013</year>
<volume>27</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>62-70</page-range></nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Apfelbaum]]></surname>
<given-names><![CDATA[JL]]></given-names>
</name>
<name>
<surname><![CDATA[Chen]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Mehta]]></surname>
<given-names><![CDATA[SS]]></given-names>
</name>
<name>
<surname><![CDATA[Gan]]></surname>
<given-names><![CDATA[TJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged]]></article-title>
<source><![CDATA[Anesth Analg]]></source>
<year>2003</year>
<volume>97</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>534-40</page-range></nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Buvanendran]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Fiala]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Patel]]></surname>
<given-names><![CDATA[KA]]></given-names>
</name>
<name>
<surname><![CDATA[Golden]]></surname>
<given-names><![CDATA[AD]]></given-names>
</name>
<name>
<surname><![CDATA[Moric]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Kroin]]></surname>
<given-names><![CDATA[JS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The incidence and severity of postoperative pain following inpatient surgery]]></article-title>
<source><![CDATA[Pain Med]]></source>
<year>2015</year>
<volume>16</volume>
<numero>12</numero>
<issue>12</issue>
<page-range>2277-83</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sadhasivam]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Chidambaran]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Pharmacogenomics of opioids and perioperative pain management]]></article-title>
<source><![CDATA[Pharmacogenomics]]></source>
<year>2012</year>
<volume>13</volume>
<numero>15</numero>
<issue>15</issue>
<page-range>1719-40</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Viscusi]]></surname>
<given-names><![CDATA[ER]]></given-names>
</name>
<name>
<surname><![CDATA[Skobieranda]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Soergel]]></surname>
<given-names><![CDATA[DG]]></given-names>
</name>
<name>
<surname><![CDATA[Cook]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Burt]]></surname>
<given-names><![CDATA[DA]]></given-names>
</name>
<name>
<surname><![CDATA[Singla]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[APOLLO-1: a randomized placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the µ-opioid receptor, for management of moderate-to-severe acute pain following bunionectomy]]></article-title>
<source><![CDATA[J Pain Res]]></source>
<year>2019</year>
<volume>12</volume>
<page-range>927-43</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Singla]]></surname>
<given-names><![CDATA[NK]]></given-names>
</name>
<name>
<surname><![CDATA[Skobieranda]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Soergel]]></surname>
<given-names><![CDATA[DG]]></given-names>
</name>
<name>
<surname><![CDATA[Salamea]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Burt]]></surname>
<given-names><![CDATA[DA]]></given-names>
</name>
<name>
<surname><![CDATA[Demitrack]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[APOLLO-2: A randomized, placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the µ-opioid receptor, for management of moderate to severe acute pain following abdominoplasty]]></article-title>
<source><![CDATA[Pain Pract]]></source>
<year>2019</year>
<volume>19</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>715-31</page-range></nlm-citation>
</ref>
<ref id="B14">
<label>14</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Bergese]]></surname>
<given-names><![CDATA[SD]]></given-names>
</name>
<name>
<surname><![CDATA[Brzezinski]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Hammer]]></surname>
<given-names><![CDATA[GB]]></given-names>
</name>
<name>
<surname><![CDATA[Beard]]></surname>
<given-names><![CDATA[TL]]></given-names>
</name>
<name>
<surname><![CDATA[Pan]]></surname>
<given-names><![CDATA[PH]]></given-names>
</name>
<name>
<surname><![CDATA[Mace]]></surname>
<given-names><![CDATA[SE]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[ATHENA: a phase 3, open-label study of the safety and effectiveness of oliceridine (TRV130), a G-protein selective agonist at the µ-opioid receptor, in patients with moderate to severe acute pain requiring parenteral opioid therapy]]></article-title>
<source><![CDATA[J Pain Res]]></source>
<year>2019</year>
<volume>12</volume>
<page-range>3113-26</page-range></nlm-citation>
</ref>
<ref id="B15">
<label>15</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Violin]]></surname>
<given-names><![CDATA[JD]]></given-names>
</name>
<name>
<surname><![CDATA[Crombie]]></surname>
<given-names><![CDATA[AL]]></given-names>
</name>
<name>
<surname><![CDATA[Soergel]]></surname>
<given-names><![CDATA[DG]]></given-names>
</name>
<name>
<surname><![CDATA[Lark]]></surname>
<given-names><![CDATA[MW]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Biased ligands at G-protein-coupled receptors: promise and progress]]></article-title>
<source><![CDATA[Trends Pharmacol Sci]]></source>
<year>2014</year>
<volume>35</volume>
<numero>7</numero>
<issue>7</issue>
<page-range>308-16</page-range></nlm-citation>
</ref>
<ref id="B16">
<label>16</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Manglik]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Lin]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
<name>
<surname><![CDATA[Aryal]]></surname>
<given-names><![CDATA[DK]]></given-names>
</name>
<name>
<surname><![CDATA[McCorvy]]></surname>
<given-names><![CDATA[JD]]></given-names>
</name>
<name>
<surname><![CDATA[Dengler]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Corder]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Structure-based discovery of opioid analgesics with reduced side effects]]></article-title>
<source><![CDATA[Nature]]></source>
<year>2016</year>
<volume>537</volume>
<numero>619</numero>
<issue>619</issue>
<page-range>185-90</page-range></nlm-citation>
</ref>
<ref id="B17">
<label>17</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Váradi]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Marrone]]></surname>
<given-names><![CDATA[GF]]></given-names>
</name>
<name>
<surname><![CDATA[Palmer]]></surname>
<given-names><![CDATA[TC]]></given-names>
</name>
<name>
<surname><![CDATA[Narayan]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Szabo]]></surname>
<given-names><![CDATA[MR]]></given-names>
</name>
<name>
<surname><![CDATA[Le Rouzic]]></surname>
<given-names><![CDATA[V]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Mitragynine/corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism, which do not recruit ß-arrestin-2]]></article-title>
<source><![CDATA[J Med Chem]]></source>
<year>2016</year>
<volume>59</volume>
<numero>18</numero>
<issue>18</issue>
<page-range>8381-97</page-range></nlm-citation>
</ref>
<ref id="B18">
<label>18</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Koblish]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Carr]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Siuda]]></surname>
<given-names><![CDATA[ER]]></given-names>
</name>
<name>
<surname><![CDATA[Rominger]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Gowen-MacDonald]]></surname>
<given-names><![CDATA[W]]></given-names>
</name>
<name>
<surname><![CDATA[Cowan]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[TRV0109101, a G protein-biased agonist of the µ-opioid receptor, does not promote opioid-induced mechanical allodynia following chronic administration]]></article-title>
<source><![CDATA[J Pharmacol Exp Ther]]></source>
<year>2017</year>
<volume>362</volume>
<numero>2</numero>
<issue>2</issue>
<page-range>254-62</page-range></nlm-citation>
</ref>
<ref id="B19">
<label>19</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Schmid]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
<name>
<surname><![CDATA[Kennedy]]></surname>
<given-names><![CDATA[NM]]></given-names>
</name>
<name>
<surname><![CDATA[Ross]]></surname>
<given-names><![CDATA[NC]]></given-names>
</name>
<name>
<surname><![CDATA[Lovell]]></surname>
<given-names><![CDATA[KM]]></given-names>
</name>
<name>
<surname><![CDATA[Yue]]></surname>
<given-names><![CDATA[Z]]></given-names>
</name>
<name>
<surname><![CDATA[Morgenweck]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Bias factor and therapeutic window correlate to predict safer opioid analgesics]]></article-title>
<source><![CDATA[Cell]]></source>
<year>2017</year>
<volume>171</volume>
<numero>5</numero>
<issue>5</issue>
<page-range>1165-75</page-range></nlm-citation>
</ref>
<ref id="B20">
<label>20</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Bohn]]></surname>
<given-names><![CDATA[LM]]></given-names>
</name>
<name>
<surname><![CDATA[Dykstra]]></surname>
<given-names><![CDATA[LA]]></given-names>
</name>
<name>
<surname><![CDATA[Lefkowitz]]></surname>
<given-names><![CDATA[RJ]]></given-names>
</name>
<name>
<surname><![CDATA[Caron]]></surname>
<given-names><![CDATA[MG]]></given-names>
</name>
<name>
<surname><![CDATA[Barak]]></surname>
<given-names><![CDATA[LS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Relative opioid efficacy is determined bycthe complements of the G protein-coupled receptor desensitization machinery]]></article-title>
<source><![CDATA[Mol Pharmacol]]></source>
<year>2004</year>
<volume>66</volume>
<numero>1</numero>
<issue>1</issue>
<page-range>106-12</page-range></nlm-citation>
</ref>
<ref id="B21">
<label>21</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Raehal]]></surname>
<given-names><![CDATA[KM]]></given-names>
</name>
<name>
<surname><![CDATA[Walker]]></surname>
<given-names><![CDATA[JK]]></given-names>
</name>
<name>
<surname><![CDATA[Bohn]]></surname>
<given-names><![CDATA[LM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Morphine side effects in beta-arrestin 2 knockout mice]]></article-title>
<source><![CDATA[J Pharmacol Exp Ther]]></source>
<year>2005</year>
<volume>314</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>1195-201</page-range></nlm-citation>
</ref>
<ref id="B22">
<label>22</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Bohn]]></surname>
<given-names><![CDATA[LM]]></given-names>
</name>
<name>
<surname><![CDATA[Lefkowitz]]></surname>
<given-names><![CDATA[RJ]]></given-names>
</name>
<name>
<surname><![CDATA[Gainetdinov]]></surname>
<given-names><![CDATA[RR]]></given-names>
</name>
<name>
<surname><![CDATA[Peppel]]></surname>
<given-names><![CDATA[K]]></given-names>
</name>
<name>
<surname><![CDATA[Caron]]></surname>
<given-names><![CDATA[MG]]></given-names>
</name>
<name>
<surname><![CDATA[Lin]]></surname>
<given-names><![CDATA[FT]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Enhanced morphine analgesia in mice lacking beta-arrestin 2]]></article-title>
<source><![CDATA[Science]]></source>
<year>1999</year>
<volume>286</volume>
<numero>5449</numero>
<issue>5449</issue>
<page-range>2495-8</page-range></nlm-citation>
</ref>
<ref id="B23">
<label>23</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Viscusi]]></surname>
<given-names><![CDATA[ER]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Improving the therapeutic window of conventional opioids: novel differential signaling modulators]]></article-title>
<source><![CDATA[Reg Anesth Pain Med]]></source>
<year>2019</year>
<volume>44</volume>
<page-range>32-7</page-range></nlm-citation>
</ref>
<ref id="B24">
<label>24</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Lötsch]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Geisslinger]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Relevance of frequent mu-opioid receptor polymorphisms for opioid activity in healthy volunteers]]></article-title>
<source><![CDATA[Pharmacogenomics J]]></source>
<year>2006</year>
<volume>6</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>200-10</page-range></nlm-citation>
</ref>
<ref id="B25">
<label>25</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Schneider]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Provasi]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Filizola]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[How oliceridine (TRV-130) binds and stabilizes a µ-opioid receptor conformational state that selectively triggers g protein signaling pathways]]></article-title>
<source><![CDATA[Biochemistry]]></source>
<year>2016</year>
<volume>55</volume>
<numero>46</numero>
<issue>46</issue>
<page-range>6456-66</page-range></nlm-citation>
</ref>
<ref id="B26">
<label>26</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Soergel]]></surname>
<given-names><![CDATA[DG]]></given-names>
</name>
<name>
<surname><![CDATA[Subach]]></surname>
<given-names><![CDATA[RA]]></given-names>
</name>
<name>
<surname><![CDATA[Sadler]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Connell]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Marion]]></surname>
<given-names><![CDATA[AS]]></given-names>
</name>
<name>
<surname><![CDATA[Cowan]]></surname>
<given-names><![CDATA[CL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in healthy volunteers]]></article-title>
<source><![CDATA[J Clin Pharmacol]]></source>
<year>2014</year>
<volume>54</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>351-7</page-range></nlm-citation>
</ref>
<ref id="B27">
<label>27</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Soergel]]></surname>
<given-names><![CDATA[DG]]></given-names>
</name>
<name>
<surname><![CDATA[Subach]]></surname>
<given-names><![CDATA[RA]]></given-names>
</name>
<name>
<surname><![CDATA[Burnham]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
<name>
<surname><![CDATA[Lark]]></surname>
<given-names><![CDATA[MW]]></given-names>
</name>
<name>
<surname><![CDATA[James]]></surname>
<given-names><![CDATA[IE]]></given-names>
</name>
<name>
<surname><![CDATA[Sadler]]></surname>
<given-names><![CDATA[BM]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Biased agonism of the µ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers]]></article-title>
<source><![CDATA[Pain]]></source>
<year>2014</year>
<volume>155</volume>
<numero>9</numero>
<issue>9</issue>
<page-range>1829-35</page-range></nlm-citation>
</ref>
<ref id="B28">
<label>28</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Markham]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Oliceridine: first approval]]></article-title>
<source><![CDATA[Drugs]]></source>
<year>2020</year>
<volume>80</volume>
<numero>16</numero>
<issue>16</issue>
<page-range>1739-44</page-range></nlm-citation>
</ref>
<ref id="B29">
<label>29</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Dahan]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[van Dam]]></surname>
<given-names><![CDATA[CJ]]></given-names>
</name>
<name>
<surname><![CDATA[Niesters]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[van Velzen]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[Fossler]]></surname>
<given-names><![CDATA[MJ]]></given-names>
</name>
<name>
<surname><![CDATA[Demitrack]]></surname>
<given-names><![CDATA[MA]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Benefit and risk evaluation of biased µ-receptor agonist oliceridine versus morphine]]></article-title>
<source><![CDATA[Anesthesiology]]></source>
<year>2020</year>
<volume>133</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>559-68</page-range></nlm-citation>
</ref>
<ref id="B30">
<label>30</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Tan]]></surname>
<given-names><![CDATA[HS]]></given-names>
</name>
<name>
<surname><![CDATA[Habib]]></surname>
<given-names><![CDATA[AS]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Oliceridine: a novel drug for the management of moderate to severe acute pain - A review of current evidence]]></article-title>
<source><![CDATA[J Pain Res]]></source>
<year>2021</year>
<volume>14</volume>
<page-range>969-79</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
