Opioid receptors and their relevance to anaesthesia.

The therapeutic entities which have been derived from the constituents of opium, the dried exudate of the incised capsule of the opium poppy, have probably spawned more scientific publications than any other drug group. The observations that only the laevorotatory isomer of morphine, the active constituent of opium, was active and that most opioid analgesic drugs had similarities in structure, prompted Beckett and Casey to propose a tentative structure for an opioid receptor [4]. Since then our understanding of opioid pharmacology has progressed steadily with the notable highs of the discovery of the endogenous ligands to the opioid receptor [37] and the overwhelming evidence of multiple opioid receptors first noted by Martin and colleagues [56]. The anaesthetist uses morphine and its derivatives most commonly as analgesics for moderate to severe pain. With adjustment of dose and route of administration, opioids may perform this function with the minimum of side effects, which may range from the uncomfortable (itching, nausea and vomiting) to the life-threatening (respiratory depression). Chronic use of opioids may also lead to tolerance and physical dependence. It is worth re-emphasizing the theme which runs through most recent reviews of any aspect of opioid activity: "It was hoped that the development of opioid agonists selective for a particular opioid receptor subtype might separate the useful actions of opioids from the rest, and result in a therapeutic breakthrough. This breakthrough has not occurred!" What then, is the relevance of the subdivisions of opioid receptors to the anaesthetist?