Multiple ligands in opioid research.
The observation in 1979 that opioid receptors interact, led to the design of bivalent ligands in an attempt to improve selectivity and affinity towards the different subtypes( i.e. mu, delta, and kappa). Dimers of monovalent 'parent' opioid structures have been evaluated and include: (a) endogenous (e.g enkephalins) or exogenous (e.g dermorphin) peptide dimer analogues (b) mixed peptidic -non-peptidic bivalent ligands and (c) dual non-peptidic dimers. Chimeric structures, using an opioid pharmacophore in combination with a a non-opioid pharmacophore, have also been prepared. The common aim in all these studies is to improve the pharmacological profile of potential analgesics to minimize common opioid-induced side effects, such as physical dependence and tolerance. Here we present a brief overview efforts to develop bivalent opioid ligands for use in pain-related research.
Ballet
Steven
S
School of Chemistry and Physics, University of Adelaide, North Terrace, Adelaide SA 5005, Australia. steven.ballet@adelaide.edu.au
Pietsch
Markus
M
Abell
Andrew D
AD
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D019281:Dimerization; D015195:Drug Design; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011957:Receptors, Opioid / Q000737:chemistry / Q000145:classification / Q000378:metabolism
D000701:Analgesics, Opioid; D008024:Ligands; D010455:Peptides; D011957:Receptors, Opioid