Buprenorphine, sold under the brand name Subutex among others, is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection, as a skin patch (transdermal), or as an implant. For opioid use disorder, the patient must have moderate opioid withdrawal symptoms before buprenorphine can be administered under direct observation of a health-care provider.
Etorphine (M99) is a semi-synthetic opioid possessing an analgesic potency approximately 1,000–3,000 times that of morphine. It was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather the related plants Papaver orientale and Papaver bracteatum. It was reproduced in 1963 by a research group at MacFarlan Smith in Gorgie, Edinburgh, led by Kenneth Bentley. It can be produced from thebaine.
Opioid peptides or opiate peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but they all resemble those of opiates. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, control of food intake, and the rewarding effects of alcohol and nicotine.
Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor. Nociceptin acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers; its activation is associated with brain functions such as pain sensation and fear learning.
The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the OPRL1 gene. The nociceptin receptor is a member of the opioid subfamily of G protein-coupled receptors whose natural ligand is the 17 amino acid neuropeptide known as nociceptin (N/OFQ). This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors. Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease, whereas NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates.
Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.
JTC-801 is an opioid analgesic drug used in scientific research.
Xorphanol (INN), also known as xorphanol mesylate (USAN), is an opioid analgesic of the morphinan family that was never marketed.
J-113,397 is an opioid drug which was the first compound found to be a highly selective antagonist for the nociceptin receptor, also known as the ORL-1 receptor. It is several hundred times selective for the ORL-1 receptor over other opioid receptors, and its effects in animals include preventing the development of tolerance to morphine, the prevention of hyperalgesia induced by intracerebroventricular administration of nociceptin, as well as the stimulation of dopamine release in the striatum, which increases the rewarding effects of cocaine, but may have clinical application in the treatment of Parkinson's disease.
SB-612,111 is an opioid receptor ligand which is a potent and selective antagonist for the nociceptin receptor (ORL-1), several times more potent than the older drug J-113,397. It does not have analgesic effects in its own right, but prevents the development of hyperalgesia, and also shows antidepressant effects in animal studies.
Ro64-6198 is an opioid drug used in scientific research. It acts as a potent and selective agonist for the nociceptin receptor, also known as the ORL-1 receptor, with over 100x selectivity over the other opioid receptors. It produces anxiolytic effects in animal studies equivalent to those of benzodiazepine drugs, but has no anticonvulsant effects and does not produce any overt effects on behaviour. However it does impair short-term memory, and counteracts stress-induced anorexia. It also has antitussive effects, and reduces the rewarding and analgesic effects of morphine, although it did not prevent the development of dependence. It has been shown to reduce alcohol self-administration in animals and suppressed relapses in animal models of alcoholism, and ORL-1 agonists may have application in the treatment of alcoholism.
JDTic is a selective, long-acting ("inactivating") antagonist of the κ-opioid receptor (KOR). JDTic is a 4-phenylpiperidine derivative, distantly related structurally to analgesics such as pethidine and ketobemidone, and more closely to the MOR antagonist alvimopan. In addition, it is structurally distinct from other KOR antagonists such as norbinaltorphimine. JDTic has been used to create crystal structures of KOR [ PDB: 4DJH, 6VI4].
Alazocine, also known more commonly as N-allylnormetazocine (NANM), is a synthetic opioid analgesic of the benzomorphan family related to metazocine, which was never marketed. In addition to its opioid activity, the drug is a sigma receptor agonist, and has been used widely in scientific research in studies of this receptor. Alazocine is described as a potent analgesic, psychotomimetic or hallucinogen, and opioid antagonist. Moreover, one of its enantiomers was the first compound that was found to selectively label the σ1 receptor, and led to the discovery and characterization of the receptor.
MCOPPB is a drug which acts as a potent and selective agonist for the nociceptin receptor, with a pKi of 10.07 and much weaker activity at other opioid receptors. It has only moderate affinity for the mu opioid receptor, weak affinity for the kappa opioid receptor and negligible binding at the delta opioid receptor. In animal studies, MCOPPB produces potent anxiolytic effects, with no inhibition of memory or motor function, and only slight sedative side effects which do not appear until much higher doses than the effective anxiolytic dose range.
Naltalimide (INN) (code name TRK-130, formerly TAK 363) is a novel, centrally-acting opioid drug which is under development by Takeda and Toray for the treatment of overactive bladder/urinary incontinence. It acts as a potent and selective partial agonist of the μ-opioid receptor (Ki = 0.268 nM, EC50 = 2.39 nM, Emax = 66.1%) over the δ-opioid (Ki = 121 nM, EC50 = 26.1 nM, Emax = 71.0%) and κ-opioid receptors (Ki = 8.97 nM, EC50 = 9.51 nM, Emax = 62.6%). Notably, naltalimide somehow appears to lack certain undesirable side effects such as constipation seen with other μ-opioid receptor agonists such as morphine. It enhances bladder storage via suppression of the afferent limb of the micturition reflex pathway.
Thienorphine is a very potent, extremely long-acting, orally-active opioid analgesic with mixed agonist–antagonist properties which was developed by the Beijing Institute of Pharmacology and Toxicology as a potential treatment for opioid dependence. It is a high-affinity, balanced ligand of the μ-, δ-, and κ-opioid receptors, behaving as a partial agonist of the μ- and κ-opioid receptors and as an antagonist of the δ-opioid receptor. It also possesses relatively low affinity for the nociceptin receptor, where it acts as an antagonist.
SR-16435 is a drug which acts as a potent partial agonist at both the μ-opioid receptor and nociceptin receptor. In animal studies it was found to be a potent analgesic, with results suggestive of reduced development of tolerance and increased activity against neuropathic pain compared to classic μ-selective agonists.
Sunobinop is a high affinity small molecule nociceptin receptor partial agonist.
Ro65-6570 is an opioid drug. It has a potential use in preventing the addiction to other opioids.
SCH-221510 is an experimental opioid drug. It has potential as an analgesic and as a treatment to addiction of certain drugs.
