What are their physiological and therapeutical relevance?
The previously mentioned functions of opioid receptors, as well as a number of other associated effects, reflect their importance in processes like pain, respiratory drive and mood and explain various therapeutic exploitations of opioids for sedation, antidepressants and most commonly, their use as analgesics (ex: Morphine). Opioids can also be used to treat diarrhoea, coughs and anxiety. They do have a number of side effects including respiratory depression, constipation, euphoria, sedation and withdrawal syndromes potentially leading to addiction. The differential, and sometimes opposing, effects caused by the activation of different opioid receptors relies on their differential recognition by their opioid ligands. The main (broad) types of opioid ligands are endogenous opioids, opium alkaloids, semi-synthetic opioids and fully synthetic opioids. Endogenous opioids show a defined preference for their particular subtype of opioid receptors and their structure is key to the differential stimulation of structurally very similar opioid receptors. However, exogenous opioids and synthetic opioids are known to interact much more promiscuously with opioid receptors, probably due to the similarity amoung opioid receptor binding pockets.
The elucidation of the opium receptor-opioid ligand complex has provided important clues on the molecular interactions that drive and stabilize differential receptor recognition and receptor activation events. The data from these studies has provided valuable information for the development of drug agonists or antagonists, which bring about a desired change in phenotype as a result of differential receptor stimulation. However, although medicinal chemistry has lead to the discovery of many reasonably selective opioid receptor ligands to date, there is still a substantial interest in the development of even more subtype-selective K-OR agonists and antagonists that can be exploited in the design of new pharmacological products.
The elucidation of the opium receptor-opioid ligand complex has provided important clues on the molecular interactions that drive and stabilize differential receptor recognition and receptor activation events. The data from these studies has provided valuable information for the development of drug agonists or antagonists, which bring about a desired change in phenotype as a result of differential receptor stimulation. However, although medicinal chemistry has lead to the discovery of many reasonably selective opioid receptor ligands to date, there is still a substantial interest in the development of even more subtype-selective K-OR agonists and antagonists that can be exploited in the design of new pharmacological products.
This section puts the blog into context well and shows there is a biological relevance to solving the structures talked about later.
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