In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile

Kuo, A., Wyse, B. D., Meutermans, W. and Smith, M. T. (2014) In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile. British Journal of Pharmacology, Accepted Article 2: 1-48. doi:10.1111/bph.12696

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Author Kuo, A.
Wyse, B. D.
Meutermans, W.
Smith, M. T.
Title In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile
Formatted title
In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
1476-5381
Publication date 2014-03-18
Year available 2014
Sub-type Article (original research)
DOI 10.1111/bph.12696
Open Access Status DOI
Volume Accepted Article
Issue 2
Start page 1
End page 48
Total pages 48
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted abstract
Background and Purpose 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 between-opioid differences in their in vivo pharmacodynamic profiles. Hence this study in rats was designed to investigate between-opioid differences in their in vivo profiles.

Experimental Approach Male Sprague Dawley rats were administered single intracerebroventricular (icv) bolus doses of morphine, morphine-6-glucuronide (M6G), fentanyl, oxycodone, buprenorphine, DPDPE 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.

Key Results The afore-mentioned opioids 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.

Conclusion and Implications For the seven opioids assessed herein, no two have the same profile for evoking antinociception, constipation and respiratory depression suggesting that these effects are differentially regulated. Our findings likely underpin the clinical success of ‘opioid rotation’.
Keyword Morphine
Morphine-6-glucuronide (M6G)
Oxycodone
Buprenorphine
Fentanyl
Antinociception
Constipation
Respiratory depression
Intracerebroventricular
Rat
Opioid analgesics
Analgesia
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID LP0668324
Institutional Status UQ
Additional Notes Accepted manuscript online: 18 MAR 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Pharmacy Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 23 Mar 2014, 03:06:37 EST by Professor Maree Smith on behalf of School of Pharmacy