Nociceptin receptor

An additional opioid receptor has been identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or NOP receptor. Its natural ligand is known alternately as nociceptin or orphanin FQ.

Mechanism
Nociceptin is thought to be an endogenous antagonist of dopamine transport that may act either directly on dopamine or by inhibiting GABA to affect dopamine levels. Within the central nervous system its action can be either similar or opposite to those of opioids depending on their location. It controls a wide range of biological functions ranging from nociception to food intake, from memory processes to cardiovascular and renal functions, from spontaneous locomotor activity to gastrointestinal motility, from anxiety to the control of neurotransmitter release at peripheral and central sites.

Selective Ligands
Several commonly used opioid drugs including etorphine and buprenorphine have been demonstrated to bind to nociceptin receptors, but this binding is relatively insignificant compared to their activity at other opioid receptors. More recently a range of selective ligands for ORL-1 have been developed, which show little or no affinity to other opioid receptors and so allow ORL-1 mediated responses to be studied in isolation.

Agonists

 * Nociceptin
 * Norbuprenorphine (not selective for ORL-1, also full agonist at μ-opioid receptors)
 * NNC 63-0532
 * Ro64-6198
 * Ro65-6570
 * SCH-221,510
 * SR-16435 (mixed mu / nociceptin partial agonist)

Antagonists

 * JTC-801
 * J-113,397
 * SB-612,111
 * SR-16430

Applications
ORL 1 agonists are being studied as treatments for heart failure and migraine while nociceptin antagonists such as JTC-801 may have analgesic and antidepressant qualities.

The novel drug buprenorphine is a partial agonist at ORL 1 receptors while its metabolite norbuprenorphine is a full agonist at these receptors.