Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are now four types of opioid receptors. The new designations OP(1), OP(2) and OP(3) correspond, respectively, to the classic delta-, kappa- and micro-nomenclature. OP(4) was previously known as ORL(1), the receptor for the endogenous heptadecapeptide nociceptin/orphanin FQ. Although the cellular effects of nociceptin resemble those of conventional OP(1), OP(2), and OP(3) opioid agonists, its effects on nociceptive processes are quite different. Nociceptin produces spinal analgesia but appears to antagonize the effects of opioids. Following the recent synthesis of the nonpeptide OP(4) agonist Ro-64-6198 by Hoffmann-La Roche and the nonpeptide OP(4) antagonist J-113397 by Banyu, the nociceptin-OP(4) system now represents a viable and intriguing new target for drug design. OP(4) agonists may be of use in the management of neuropathic pain, anxiety, anorexia, epilepsy, drug dependence, male impotence, hypertension, cerebral ischemia and neurogenic bladder. They may also serve as novel diuretics and to help to reduce gastrointestinal motility. OP(4) antagonists may be of use as general analgesics and in the improvement of memory function. This review covers the recent exciting progress in this field, compares the actions of OP(4) agonists and antagonists with those of classic opioids, and seeks to predict some of the untoward effects that may be seen with such drugs.
 ...
PMID:The nociceptin receptor as a potential target in drug design. 1281 96

The advance of functional genomics revealed the superfamily of G-protein coupled receptors (GPCRs). Hundreds of GPCRs have been cloned but many of them are orphan GPCRs with unidentified ligands. The first identified orphan GPCR is the opioid receptor like orphan receptor, ORL1. It was cloned in 1994 during the identification of opioid receptor subtypes and was de-orphanized in 1995 by the discovery of its endogenous ligand, nociceptin or orphanin FQ (N/OFQ). This receptor was renamed as N/OFQ peptide (NOP) receptor. Several selective ligands acting at NOP receptors or other anti-N/OFQ agents have been reported. These include N/OFQ-derived peptides acting as agonists (cyclo[Cys(10),Cys(14)]N/OFQ, [Arg(14), Lys(15)]N/OFQ, [pX]Phe(4)N/OFQ(1-13)-NH(2), UFP-102, [(pF)Phe(4),Aib(7), Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)) or antagonists (Phe(1)psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)-NH(2), [Nphe(1)]N/OFQ(1-13)-NH(2), UFP-101, [Nphe(1), (pF)Phe(4),Aib(7),Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)), hexapeptides, other peptide derivatives (peptide III-BTD, ZP-120, OS-461, OS-462, OS-500), non-peptide agonists (NNC 63-0532, Ro 64-6198, (+)-5a compound, W-212393, 3-(4-piperidinyl)indoles, 3-(4-piperidinyl) pyrrolo[2,3-b]pyridines) and antagonists (TRK-820, J-113397, JTC-801, octahydrobenzimidazol-2-ones, 2-(1,2,4-oxadiazol-5-yl)-1 H-indole, N-benzyl-D-prolines, SB-612111), biostable RNA Spiegelmers specific against N/OFQ, and a functional antagonist, nocistatin. Buprenorphine and naloxone benzoylhydrazone are two opioid receptor ligands showing high affinity for NOP receptors. NOP receptor agonists might be beneficial in the treatment of pain, anxiety, stress-induced anorexia, cough, neurogenic bladder, edema, drug dependence, and, less promising, in cerebral ischemia and epilepsy, while antagonists might be of help in the management of pain, depression, dementia and Parkinsonism. N/OFQ is also involved in cardiovascular, gastrointestinal and immune regulation. Altered plasma levels of N/OFQ have been reported in patients with various pain states, depression and liver diseases. This review summarizes the pharmacological characteristics of, and studies with, the available NOP receptor ligands and their possible clinical implications.
 ...
PMID:Nociceptin/orphanin FQ peptide receptors: pharmacology and clinical implications. 1726 36