Opioid receptors

centuries, both in amedicinal and ‘recreational’ manner. Indeed, findings of fossilized opium poppy seeds dating as far back as 30 000 yr ago suggest the use of opium by Neanderthal man. In 1799, Friedrich Serturner discovered the major active ingredient of opium, which he named morphine and opioid pharmacology was born. Morphine and its derivates are used today for the treatment of acute and chronic pain. It is now understood that morphine and other opioid drugs act on an endogenous opioidergic system, which is not only involved in setting pain (nociceptive) threshold and controlling nociceptive processing but also participates in modulation of gastrointestinal, endocrine and autonomic function, as well as a possible role in cognition. Evidence for the existence of multiple opioid receptor subtypes arose from work identifying the different anatomical location and pharmacological profiles of compounds that were eventually used to name them, i.e. morphine (mu), ketocyclazocine (kappa) and vas deferens (delta). Recently, a fourth opioidlike receptor has been included in the opioid receptor family and is termed the nociceptin orphanin FQ peptide receptor. Receptor nomenclature has changed numerous times but current International Union of Pharmacology (IUPHAR) opinion is MOP (mu), KOP (kappa), DOP (delta) and NOP for the nociceptin orphanin FQ peptide receptor. All four are G-protein-coupled receptors sharing the similar seven transmembrane topology (Fig. 1). Other receptor subtypes have been suggested (e.g. sigma receptor) but have been dismissed based on a lack of naloxone sensitivity.