eCite Digital Repository

Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile


Dietis, ND and Guerrini, R and Calo, G and Salvadori, s and Rowbotham, DJ and Lambert, DG, Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile, British Journal of Anaesthesia, 103, (1) pp. 38-49. ISSN 1471-6771 (2009) [Substantial Review]

Not available

DOI: doi:10.1093/bja/aep129


Opioid receptors are currently classified as m (mu: mOP), d (delta: dOP), k (kappa: kOP) with a fourth related non-classical opioid receptor for nociceptin/orphainin FQ, NOP. Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side-effects, in particular tolerance. There is now good laboratory evidence to suggest that blocking DOP while activating MOP produces analgesia (or antinociception) without the development of tolerance. Simultaneous targeting of MOP and DOP can be accomplished by: (i) co-administering two selective drugs, (ii) administering one non-selective drug, or (iii) designing a single drug that specifically targets both receptors; a bivalent ligand. Bivalent ligands generally contain two active centres or pharmacophores that are variably separated by a chemical spacer and there are several interesting examples in the literature. For example linking the MOP agonist oxymorphone to the DOP antagonist naltrindole produces a MOP/DOP bivalent ligand that should produce analgesia with reduced tolerance. The type of response/selectivity produced depends on the pharmacophore combination (e.g. oxymorphone and naltrindole as above) and the space between them. Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic (and in particular cancer) pain.

Item Details

Item Type:Substantial Review
Keywords:analgesics, opioid; cancer; pharmacology, opioids; receptors, opioid; structure,
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Manufacturing
Objective Group:Human pharmaceutical products
Objective Field:Human pharmaceutical products not elsewhere classified
UTAS Author:Dietis, ND (Dr Nikolas Dietis)
ID Code:80397
Year Published:2009
Web of Science® Times Cited:129
Deposited By:Pharmacy
Deposited On:2012-10-31
Last Modified:2015-05-15

Repository Staff Only: item control page