Multiple opiate receptors: déjà vu all over again

The concept of multiple opioid receptors has changed dramatically since their initial proposal by Martin nearly 40 years ago. Three major opioid receptor families have now been proposed: mu, kappa and delta. Most of the opioid analgesics used clinically selectively bind to mu opioid receptors. Yet, clinicians have long appreciated subtle, but significant, differences in their pharmacology. These observations suggested more than one mu opioid receptor mechanism of action and led us to propose multiple mu opioid receptors over 20 years ago based upon a range of pharmacological and receptor binding approaches. A mu opioid receptor, MOR-1, was cloned about a decade ago. More recent studies have now identified a number of splice variants of this clone. These splice variants may help explain the pharmacology of the mu opioids and open interesting directions for future opioid research.