| Abstract: |
Most of the opioids used in clinical practice exert their effects through μ opioid receptors. Yet, subtle but important pharmacological differences have been observed among the μ opioids. Their potency, effectiveness, and adverse effects can vary unpredictably among patients. These clinical differences among the μ opioids strongly argue against a single receptor mediating their actions. The cloning of the μ opioid receptor has greatly enhanced our understanding of the complexity of this system and has provided possible mechanisms to explain these observations. A single μ opioid receptor gene has been identified, but we now know that it generates a multitude of different μ opioid receptor subtypes through a mechanism commonly used to enhance protein diversity, alternative splicing. Early studies identified a number of splice variants involving the tip of the C-terminus. This region of the receptor is far away from the binding pocket, explaining why these variants still exhibit the same selectivity for μ opioids. However, the differences in structure at the C-terminus influence the activation patterns of the μ opioids. In addition, a second series of variants has been isolated that involves alternative splicing at the N-terminus. Together, these sets of μ opioid receptor splice variants may help explain the clinical variability of the μ drugs among patients and provide insights into why it is so important to individualize therapy for every patient in pain. © 2010 Lippincott Williams & Wilkins, Inc. |
| Keywords: |
review; drug efficacy; nonhuman; clinical practice; animals; mice; mice, knockout; pain; protein; history, 21st century; drug potency; history, 20th century; gene identification; alternative splicing; alternative rna splicing; outpatient department; methadone; morphine; analgesics, opioid; observational study; disease models, animal; mu opiate receptor; receptors, opioid, mu; knockout mouse; comprehension; fentanyl; diamorphine; morphine 6 glucuronide; oxycodone; introspection; opioid receptor; cloning; codeine; oxymorphone; opiate analgesic; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; naloxone benzoylhydrazone
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