Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 287-296 |
| Number of pages | 10 |
| Journal | British Journal of Pharmacology |
| Volume | 172 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2015 |
Keywords
- allosterism
- biased-agonism
- GPCR
- μ-opioid receptor
Cite this
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Novel GPCR paradigms at the μ-opioid receptor. / Thompson, Georgina Louise; Kelly, Eamon; Christopoulos, Arthur; Canals, Meritxell.
In: British Journal of Pharmacology, Vol. 172, No. 2, 2015, p. 287-296.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Novel GPCR paradigms at the μ-opioid receptor
AU - Thompson, Georgina Louise
AU - Kelly, Eamon
AU - Christopoulos, Arthur
AU - Canals, Meritxell
PY - 2015
Y1 - 2015
N2 - Opioids, such as morphine, are the most clinically useful class of analgesic drugs for the treatment of acute and chronic pain. However, the use of opioids is greatly limited by the development of severe adverse side effects. Consequently, drug discovery efforts have been directed towards improving the therapeutic profile of opioid-based treatments. Opioid receptors are members of the family of GPCRs. As such, the recent GPCR paradigms of biased agonism and allosterism may provide novel avenues for more effective analgesics. Biased agonism (or functional selectivity) has been described for all the opioid receptor family members. Furthermore, the first allosteric modulators of opioid receptors have very recently been described. However, identification and quantification of biased agonism in a manner that is informative to medicinal chemists and drug discovery programmes still remains a challenge. In this review, we examine the progress, to date, towards identification and quantification of biased agonism and allosterism at the μ-opioid receptor in the context of its implications for the discovery of better and safer analgesics.
AB - Opioids, such as morphine, are the most clinically useful class of analgesic drugs for the treatment of acute and chronic pain. However, the use of opioids is greatly limited by the development of severe adverse side effects. Consequently, drug discovery efforts have been directed towards improving the therapeutic profile of opioid-based treatments. Opioid receptors are members of the family of GPCRs. As such, the recent GPCR paradigms of biased agonism and allosterism may provide novel avenues for more effective analgesics. Biased agonism (or functional selectivity) has been described for all the opioid receptor family members. Furthermore, the first allosteric modulators of opioid receptors have very recently been described. However, identification and quantification of biased agonism in a manner that is informative to medicinal chemists and drug discovery programmes still remains a challenge. In this review, we examine the progress, to date, towards identification and quantification of biased agonism and allosterism at the μ-opioid receptor in the context of its implications for the discovery of better and safer analgesics.
KW - allosterism
KW - biased-agonism
KW - GPCR
KW - μ-opioid receptor
UR - http://onlinelibrary.wiley.com.ezproxy.lib.monash.edu.au/doi/10.1111/bph.12600/epdf
U2 - 10.1111/bph.12600
DO - 10.1111/bph.12600
M3 - Article
VL - 172
SP - 287
EP - 296
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 1476-5381
IS - 2
ER -