In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile. (1st July 2014)

• Record Type: Journal Article
• Authors: Kuo, A; Wyse, B D; Meutermans, W; Smith, M T
• Is Part Of: British journal of pharmacology. Volume 172:Number 2(2015:Jan.)
• Page Start: 532
• Page End: 548
• Publication Date: 2014-07-01
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12696
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12696-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>For patients experiencing inadequate analgesia and intolerable opioid‐related side effects on one strong opioid analgesic, pain relief with acceptable tolerability is often achieved by rotation to a second strong opioid. These observations suggest subtle pharmacodynamic differences between opioids <italic>in vivo.</italic> This study in rats was designed to assess differences between opioids in their <italic>in vivo</italic> profiles.</p> </sec> <sec id="bph12696-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Male Sprague Dawley rats were given single i.c.v. bolus doses of morphine, morphine‐6‐glucuronide (M6G), fentanyl, oxycodone, buprenorphine, DPDPE ([D‐penicillamine<sup>2, 5</sup>]‐enkephalin) or U69, 593. Antinociception, constipation and respiratory depression were assessed using the warm water tail‐flick test, the castor oil‐induced diarrhoea test and whole body plethysmography respectively.</p> </sec> <sec id="bph12696-sec-0003" sec-type="section"> <title>Key Results</title> <p>These opioid agonists produced dose‐dependent antinociception, constipation and respiratory depression. For antinociception, morphine, fentanyl and oxycodone were full agonists, buprenorphine and M6G were partial agonists, whereas DPDPE and U69, 593 had low potency. For constipation, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, morphine produced a bell‐shaped dose–response curve, whereas DPDPE and U69, 593 were inactive. For respiratory depression, morphine, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, whereas DPDPE and U69, 593 were inactive. The respiratory depressant effects of fentanyl and oxycodone were of short duration, whereas morphine, M6G and buprenorphine evoked prolonged respiratory depression.</p> </sec> <sec id="bph12696-sec-0004" sec-type="section"> <title>Conclusion and Implications</title> <p>For the seven opioids we assessed, no two had the same profile for evoking antinociception, constipation and respiratory depression, suggesting that these effects are differentially regulated. Our findings may explain the clinical success of 'opioid rotation'.</p> </sec> <sec id="bph12696-sec-5001" sec-type="relatedArticles"> <title>Linked Articles</title> <p>This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1111/bph.2015.172.issue-2" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">http://dx.doi.org/10.1111/bph.2015.172.issue-2</ext-link></p> </sec> </abstract>