 | |
| Identifiers | |
|---|---|
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C30H34FN3O2 |
| Molar mass | 487.619 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  | |
DPI-3290 was discovered by scientists at Burroughs Wellcome and licensed to Delta Pharmaceutical [1] and is a drug that is used in scientific research. It is a potent analgesic drug, [2] which produces little respiratory depression. [3]
DPI-3290 acts as an agonist at both μ- and δ-opioid receptor, with an IC50 of 6.2nM at μ and 1.0nM at δ. [4]
Norbuprenorphine is a major active metabolite of the opioid modulator buprenorphine. It is a μ-opioid, δ-opioid, and nociceptin receptor full agonist, and a κ-opioid receptor partial agonist. In rats, unlike buprenorphine, norbuprenorphine produces marked respiratory depression but with very little antinociceptive effect. In explanation of these properties, norbuprenorphine has been found to be a high affinity P-glycoprotein substrate, and in accordance, shows very limited blood-brain-barrier penetration.
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.
The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligands. The regions of the brain where the δ-opioid receptor is largely expressed vary from species model to species model. In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain.
SNC-80 is an opioid analgesic drug that selectively activates μ–δ opioid receptor heteromers and is used in scientific research. It was discovered in 1994.
(+)-BW373U86 is an opioid analgesic drug used in scientific research.
14-Methoxymetopon is an experimental opioid drug developed by a team led by Professor Helmut Schmidhammer at the University of Insbruck in the mid 1990s. It is a derivative of metopon in which a methoxy group has been inserted at the 14-position. It is a highly potent analgesic drug that is around 500 times stronger than morphine when administered systemically; however, when given spinally or supraspinally, it exhibits analgesic activity up to a million fold greater than morphine. It binds strongly to the μ-opioid receptor and activates it to a greater extent than most similar opioid drugs. This produces an unusual pharmacological profile, and although 14-methoxymetopon acts as a potent μ-opioid full agonist in regard to some effects such as analgesia, a ceiling effect is seen on other effects such as constipation and respiratory depression which is believed to involve interaction with the κ-opioid receptor
DPI-221 is an opioid drug that is used in scientific research. It is a highly selective agonist for the δ-opioid receptor, which produces fewer convulsions than most drugs from this family.
RWJ-394674 is a drug that is used in scientific research. It is a potent, orally active analgesic drug that produces little respiratory depression. RWJ-394674 itself is a potent and selective agonist for δ-opioid receptors, with a Ki of 0.24 nM at δ and 72 nM at μ. However once inside the body, RWJ-394674 is dealkylated to its monodesethyl metabolite RWJ-413216, which is a potent agonist at the μ-opioid receptor and has less affinity for δ. The effect of RWJ-394674 when administered in vivo thus produces potent agonist effects at both μ and δ receptors through the combined actions of the parent drug and its active metabolite, with the δ-agonist effects counteracting the respiratory depression from the μ-opioid effects, and the only prominent side-effect being sedation.
SC-17599 is a steroid derivative drug discovered in 1968 which acts as a selective μ-opioid receptor agonist, with little or no affinity for the δ-opioid or κ-opioid receptors. It is an active analgesic in vivo, more potent than codeine or pethidine but slightly less potent than morphine, and produces similar effects to morphine in animals but with less sedation
GR-89696 is a drug which acts as a highly selective κ-opioid agonist. It shows selective effects in different animal models and it is thought it may be a subtype-selective agonist for the κ2 subtype. Recent studies have suggested that GR-89696 and related κ2-selective agonists may be useful for preventing the itching which is a common side effect of conventional opioid analgesic drugs, without the additional side effects of non-selective kappa agonists.
IBNtxA, or 3-iodobenzoyl naltrexamine, is an atypical opioid analgesic drug derived from naltrexone. In animal studies it produces potent analgesic effects that are blocked by levallorphan and so appear to be μ-opioid mediated, but it fails to produce constipation or respiratory depression, and is neither rewarding or aversive in conditioned place preference protocols. These unusual properties are thought to result from agonist action at a splice variant or heterodimer of the μ-opioid receptor, rather than at the classical full length form targeted by conventional opioid drugs.
Biphalin is a dimeric enkephalin endogenous peptide (Tyr-D-Ala-Gly-Phe-NH)2 composed of two tetrapeptides derived from enkephalins, connected 'tail-to-tail' by a hydrazide bridge. The presence of two distinct pharmacophores confers on biphalin a high affinity for both μ and δ opioid receptors (with an EC50 of about 1-5 nM for both μ and δ receptors), therefore it has analgesic activity. Biphalin presents a considerable antinociceptive profile. In fact, when administered intracerebroventricularly in mice, biphalin displays a potency almost 7-fold greater than that of the ultra-potent alkaloid agonist, etorphine and 7000-fold greater than morphine; biphalin and morphine were found to be equipotent after intraperitoneal administration. The extraordinary in vivo potency shown by this compound is coupled with low side-effects, in particular, to produce no dependency in chronic use. For these reasons, several efforts have been carried out in order to obtain more information about structure-activity relationship (SAR). Results clearly indicate that, at least for μ receptor binding, the presence of two pharmacophores is not necessary; Tyr1 is indispensable for analgesic activity, while replacing Phe at the position 4 and 4' with non-aromatic, but lipophilic amino acids does not greatly change the binding properties and in general 4,4' positions are found to be important to design biphalin analogues with increased potency and modified μ/δ selectivity. The hydrazide linker is not fundamental for activity or binding, and it can be conveniently substituted by different conformationally constrained cycloaliphatic diamine linkers.
CR665 (H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-Picolyl), also known by the previous developmental code names FE-200665 and JNJ-38488502, is an all D-amino acid peptide that acts as a peripherally restricted κ-opioid receptor agonist. The selectivity for FE 200665 is 1/16,900/84,600 for the human κ, μ, and δ opioid receptors, respectively. The dose of FE 200665 required to produce motor impairment was 548 times higher than the dose required for antinociceptive activity. It is being developed for use by Cara Therapeutics under the code name CR665.
Cebranopadol is an opioid analgesic of the benzenoid class which is currently under development internationally by Grünenthal, a German pharmaceutical company, and its partner Depomed, a pharmaceutical company in the United States, for the treatment of a variety of different acute and chronic pain states. As of November 2014, it is in phase III clinical trials.
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.
PZM21 is an experimental opioid analgesic drug that is being researched for the treatment of pain. It is claimed to be a functionally selective μ-opioid receptor agonist which produces μ-opioid receptor mediated G protein signaling, with potency and efficacy similar to morphine, but with less β-arrestin 2 recruitment. However, recent reports highlight that this might be due to its low intrinsic efficacy, rather than functional selectivity or 'G protein bias' as initially reported. In tests on mice, PZM21 was slightly less potent than morphine or TRV130 as an analgesic, but also had significantly reduced adverse effects, with less constipation than morphine, and very little respiratory depression, even at high doses. This research was described as a compelling example of how modern high-throughput screening techniques can be used to discover new chemotypes with specific activity profiles, even at targets such as the μ-opioid receptor which have already been thoroughly investigated. More recent research has suggested however that at higher doses, PZM21 is capable of producing classic opioid side effects such as respiratory depression and development of tolerance and may have only limited functional selectivity.
Peripherally acting μ-opioid receptor antagonists (PAMORAs) are a class of chemical compounds that are used to reverse adverse effects caused by opioids interacting with receptors outside the central nervous system (CNS), mainly those located in the gastrointestinal tract. PAMORAs are designed to specifically inhibit certain opioid receptors in the gastrointestinal tract and with limited ability to cross the blood-brain barrier. Therefore, PAMORAs do not affect the analgesic effects of opioids within the central nervous system.