Published online Mar 9, 2015. doi: 10.5497/wjp.v4.i1.144
Peer-review started: July 15, 2014
First decision: August 28, 2014
Revised: January 27, 2015
Accepted: February 9, 2015
Article in press: February 11, 2015
Published online: March 9, 2015
Protein to protein interactions leading to homo/heteromerization of receptor is well documented in literature. These interactions leading to dimeric/oligomers formation of receptors are known to modulate their function, particularly in case of G-protein coupled receptors. The opioid receptor heteromers having changed pharmacological properties than the constituent protomers provides preferences for novel drug targets that could lead to potential analgesic activity devoid of tolerance and physical dependence. Heterodimerization of opioid receptors appears to generate novel binding properties with improved specificity and lack of side effects. Further the molecules which can interact simultaneously to both the protomers of the heteromer, or to both the binding sites (orthosteric and allosteric) of a receptor protein could be potential therapeutic molecules. This review highlights the recent advancements in exploring the plausible role of heteromerization of opioid receptors in induction of tolerance free antinociception.
Core tip: Endogenous opioid peptides are known for their analgesic effects. However their analgesic effect is downplayed by the side-effect of tolerance development. To maintain homeostasis to their effect, other endogenous anti-opioid peptides works parallel to it. The present work highlights the role of anti-opiates in development of tolerance to opiate drugs.