Opioid analgesics receptor types

These differences in the behavioural properties of the opioid receptor sub-types are of considerable interest because the clinical use of currently marketed opioid analgesic drugs is limited by their undesirable side-effects, which include respiratory depression, constipation and an abuse or dependence liability. These side-effects have been associated with mu receptor ac-... 

Peptide transmitters Many peptides have been identified in the CNS, and some meet most or all of the criteria for acceptance as neurotransmitters. The best-defined ones are the opioid peptides (beta-endorphin, met- and leu-enkephalin, and dynorphin), which are distributed at all levels of the neuraxis. Some of the important therapeutic actions of opioid analgesics (eg, morphine) are mediated by receptors for these endogenous peptides. Substance P is localized in type C neurons involved in nociceptive sensory pathways in the spinal cord. Peptide transmitters differ from nonpeptide transmitters in that (1) the peptides are synthesized in the cell body and transported to the nerve ending via axonal transport, and (2) no reuptake or specific enzyme mechanisms have been identified for terminating their actions. 

The balance between hydrophobicity and hydrophilicity also determines the clinical characteristics of opioid analgesics, compounds that reduce pain without reducing consciousness (much). Dozens of opioids are in routine clinical use, and one reason so many are available is that they have different onset times and durations of action. This allows clinicians to choose the right one for a given circumstance. Most opioid drugs interact with a single type of receptor, the p-opiate receptor, which, like most cellular components, is lipophilic. Consequently, the primary determinant of onset time is lipophilicity, just as it is for local anesthetics and nonsteroidal anti-inflammatory drugs. 

It is now widely accepted that there are at least three opioid receptor sub-types, mu kappa and delta. During the last decade increasing evidence has accumulated to support the hypothesis that a selective kappa opioid agonist will be a powerful analgesic without the clinically limiting side-effects that characterise morphine (e.g., respiratory depression, constipation, addiction)... 

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