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| Molar mass | 393.483 g·mol−1 |
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RAM-378 [1] (7,8-Dihydro-14-hydroxy-N-phenethylnormorphine) is an opioid analgesic. It is the N-phenethyl derivative of hydromorphinol.
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). Opioid receptors are distributed widely in the brain, in the spinal cord, on peripheral neurons, and digestive tract.
Metopon (5-methylhydromorphone) is an opioid analogue that is a methylated derivative of hydromorphone which was invented in 1929 as an analgesic.
Ohmefentanyl is an extremely potent opioid analgesic drug which selectively binds to the µ-opioid receptor.
Phenomorphan is an opioid analgesic. It is not currently used in medicine, but has similar side-effects to other opiates, which include itching, nausea and respiratory depression.
Phenazocine is an opioid analgesic drug, which is related to pentazocine and has a similar profile of effects.
Normorphine is an opiate analogue, the N-demethylated derivative of morphine, that was first described in the 1950s when a large group of N-substituted morphine analogues were characterized for activity. The compound has relatively little opioid activity in its own right, but is a useful intermediate which can be used to produce both opioid antagonists such as nalorphine, and also potent opioid agonists such as N-phenethylnormorphine. with its formation from morphine catalyzed by the liver enzymes CYP3A4 and CYP2C8.
14-Phenylpropoxymetopon (PPOM) is an opiate analogue that is a derivative of metopon which has been substituted with a γ-phenylpropoxy group at the 14-position. PPOM is a highly potent analgesic drug several thousand times stronger than morphine, with an even higher in vivo potency than etorphine. The 14-phenylpropoxy substitution appears to confer potent μ-opioid agonist activity, even when combined with substitutions such as N-cyclopropyl or N-allyl, which normally result in μ-opioid antagonist compounds.
N-Phenethyl-14-ethoxymetopon is a drug that is a derivative of metopon. It is a potent analgesic, around 60 times stronger than morphine and produces significantly less constipation.
Ro4-1539 (furethylnorlevorphanol) is an opioid analgesic drug from the morphinan series that was discovered by the pharmaceutical company Hoffmann–La Roche in the 1950s. It acts as a potent μ-opioid agonist, and was found to be around 30-60 times more potent than the related drug levorphanol in animal experiments. Although it has high potency, long duration, and good therapeutic index, Ro4-1539 had no particular clinical advantages over other available opioid drugs, and was never commercially marketed.
3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ1 receptor and the serotonin transporter. The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor.
14-Cinnamoyloxycodeinone is the most potent example in a series of opiate analgesic drugs discovered in the 1960s, with > ×100 times the potency of morphine. It is a derivative of hydroxycodeinone, being the 14-cinnamate ester. In another paper, Buckett assigns the potency as 177 with a range of ×101 - ×310. It may be of interest to researchers that the allyl group in this compound and in allylprodine overlay very closely.
N-Phenethylnormorphine is an opioid analgesic drug derived from morphine by replacing the N-methyl group with β-phenethyl. It is around eight to fourteen times more potent than morphine as a result of this modification, in contrast to most other N-substituted derivatives of morphine, which are substantially less active, or act as antagonists. Binding studies have helped to explain the increased potency of N-phenethylnormorphine, showing that the phenethyl group extends out to reach an additional binding point deeper inside the μ-opioid receptor cleft, analogous to the binding of the phenethyl group on fentanyl.
8-Carboxamidocyclazocine (8-CAC) is an opioid analgesic drug related to cyclazocine, discovered by medicinal chemist Mark P. Wentland and co-workers in Cogswell Laboratory at Rensselaer Polytechnic Institute. Similarly to cyclazocine, 8-CAC acts as an agonist at both the μ and κ opioid receptors, but has a much longer duration of action than cyclazocine, and does not have μ antagonist activity. Unexpectedly it was discovered that the phenolic hydroxyl group of cyclazocine could be replaced by a carboxamido group with only slight loss of potency at opioid receptors, and this discovery has subsequently been used to develop many novel opioid derivatives where the phenolic hydroxy group has been replaced by either carboxamide or a variety of larger groups. Due to their strong κ-opioid agonist activity, these drugs are not suited for use as analgesics in humans, but have instead been researched as potential drugs for the treatment of cocaine addiction.
N-Phenethylnordesomorphine is an opiate analgesic drug derived from desomorphine by replacing the N-methyl group with β-phenethyl. Since desomorphine is already around eight times more potent than morphine, the additional boost in binding affinity produced by using the larger phenethyl group makes N-phenethylnordesomorphine a highly potent analgesic drug, some 85x more potent than morphine, and a similar strength to the closely related morphinan derivative phenomorphan.
Ciprefadol is an opioid analgesic that is an isoquinoline derivative most closely related to cyclazocine and picenadol, with a number of other related compounds known. Ciprefadol is a mixed agonist–antagonist at μ-opioid receptors and can partly block the effects of morphine at low doses, though at higher doses it acts more like a full agonist. It is also a potent κ-opioid agonist, unlike the corresponding N-methyl and N-phenethyl derivatives which are reasonably μ-selective agonists.
MR-2096 is a relatively weak opioid analgesic. It has an unusual chiral tetrahydrofuran-2-ylmethyl substitution on the nitrogen which determines the character of effects and toxicity, with the (R) enantiomer MR-2096 being an opioid agonist, while the (S) enantiomer MR-2097 has similarly potent opioid antagonist effects. This substitution makes MR 2096 completely synthetic. It does not require the use of any opium derivatives to produce. This mix of activities has made these two enantiomers useful for characterising the binding site of the mu opioid receptor. It was never marketed due to its high toxicity.
Endomorphin-1 (EM-1) (amino acid sequence Tyr-Pro-Trp-Phe-NH2) is an endogenous opioid peptide and one of the two endomorphins. It is a high affinity, highly selective agonist of the μ-opioid receptor, and along with endomorphin-2 (EM-2), has been proposed to be the actual endogenous ligand of the μ-receptor. EM-1 produces analgesia in animals and is equipotent with morphine in this regard. The gene encoding for EM-1 has not yet been identified, and it has been suggested that endomorphins could be synthesized by an enzymatic, non-ribosomal mechanism.
Axelopran is a drug which is under development by Theravance Biopharma and licensed to Glycyx for all indications. It acts as a peripherally acting μ-opioid receptor antagonist and also acts on κ-, and δ-opioid receptors, with similar affinity for the μ- and κ-opioid receptors and about an order of magnitude lower affinity for the δ-opioid receptor. Recent data suggests that μ-opioid antagonists have a direct effect on overall survival in patients with advanced cancer.
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