Etonitazene, also known as EA-4941 or CS-4640, is a benzimidazole opioid, first reported in 1957, that has been shown to have approximately 1,000 to 1,500 times the potency of morphine in animals.
7-Hydroxymitragynine is a terpenoid indole alkaloid from the plant Mitragyna speciosa, commonly known as kratom. It is often referred to as ‘7-OH’. It was first described in 1994 and is a natural product derived from the mitragynine present in the kratom leaf. It is considered an oxidized derivative and active metabolite of mitragynine. 7-OH binds to opioid receptors like mitragynine, but research suggests that 7-OH binds with greater potency and contributes heavily to the analgesic activity of mitragynine as a metabolite.
Dihydroetorphine was developed by K. W. Bentley at McFarlan-Smith in the 1960s and is a potent opioid analgesic used mainly in China. It is a derivative of the better-known opioid etorphine, a very potent veterinary painkiller and anesthetic medication used primarily for the sedation of large animals such as elephants, giraffes, and rhinos.
Oripavine is an opioid and the major metabolite of thebaine. It is the parent compound from which a series of semi-synthetic opioids are derived, which includes the compounds etorphine and buprenorphine. Although its analgesic potency is comparable to morphine, it is not used clinically due to its severe toxicity and low therapeutic index. Due to its use in manufacture of strong opioids, oripavine is a controlled substance in some jurisdictions.
Clonitazene is an opioid analgesic of approximately three times the potency of morphine. It is related to etonitazene, an opioid of significantly higher potency. Clonitazene is not currently marketed. It is a controlled substance; in the United States it is a Schedule I Narcotic controlled substance with a DEA ACSCN of 9612 and an established manufacturing quota of 25 grams for 2022.
MEPIRAPIM is an indole-based cannabinoid which differs from JWH-018 by having a 4-methylpiperazine group in place of the naphthyl group and has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan in 2013, alongside FUBIMINA. MEPIRAPIM acts as a T-type calcium channel inhibitor and is only minimally active at the central CB1 receptor.
Isotonitazene is a benzimidazole derived opioid analgesic drug related to etonitazene, which has been sold as a designer drug. It has only around half the potency of etonitazene in animal studies, but it is likely even less potent in humans as was seen with etonitazene. Isotonitazene was fully characterized in November 2019 in a paper where the authors performed a full analytical structure elucidation in addition to determination of the potency at the μ-opioid receptor using a biological functional assay in vitro. While isotonitazene was not compared directly to morphine in this assay, it was found to be around 2.5 times more potent than hydromorphone and slightly more potent than fentanyl.
Brorphine is a piperidine-based opioid analgesic compound. Brorphine was originally discovered in a 2018 paper investigating functionally biased opioid compounds, with the intention of finding safer analgesics that produce less respiratory depression than typical opioids. Brorphine was originally reported to be highly biased, with an EC50 of 4.8nM for GTPγS binding and 182nM for β-arrestin recruitment, however a more recent study found no significant bias for any of the compounds tested, including brorphine. Its safety profile in any animal model has never been established. Despite the lack of safety information on the compound, brorphine has been sold as a designer drug since mid-2019, initially being identified in the US Midwest, though it has since been found in 2020 in Belgium. It is related in chemical structure to compounds such as benzylfentanyl and bezitramide, though it is sufficiently structurally distinct to fall outside the formal definition of a "fentanyl analogue" in jurisdictions such as the US and New Zealand which have Markush structure controls over this family of drugs.
Etodesnitazene is a benzimidazole derived opioid analgesic drug, which was originally developed in the late 1950s alongside etonitazene and a range of related derivatives. It is many times less potent than etonitazene itself, but still 70x more potent than morphine in animal studies. Corresponding analogues where the N,N-diethyl group is replaced by piperidine or pyrrolidine rings also retain significant activity. Etodesnitazene has been sold as a designer drug, first being identified in both Poland and Finland in March 2020.
Kurkinorin is a non-nitrogenous, extremely selective centrally acting μ-opioid receptor agonist derived from salvinorin A with no sedating or rewarding effects.
Etonitazepipne is a benzimidazole derivative with opioid effects around 100 times more potent than morphine, which has been sold over the internet as a designer drug.
Metodesnitazene is a benzimidazole derivative with opioid effects, though unlike related compounds such as metonitazene and etodesnitazene which are many times more potent, metodesnitazene is only around the same potency as morphine in animal studies. It was proposed by the DEA to be placed under legal control in the US in December 2021.
Protonitazene is a benzimidazole derivative with potent opioid effects which has been sold over the internet as a designer drug since 2019, and has been identified in various European countries, as well as Canada, the USA and Australia. It has been linked to numerous cases of drug overdose, and is a Schedule I drug in the USA.
Butonitazene is a benzimidazole derivative with opioid effects, which has been sold over the internet as a designer drug. It has relatively low potency compared to many related compounds, and has generally been encountered as a component of mixtures with other substances rather than in its pure form. However, it is still several times the potency of morphine and has been implicated in several cases of drug overdose. Butonitazene is a Schedule I drug in the USA, along with several related compounds.
N-Desethylisotonitazene (Norisotonitazene) is a benzimidazole derivative with potent opioid effects which has been sold as a designer drug. It was first identified as an active metabolite of the related compound isotonitazene, but was unexpectedly found to be similar potency compared to the parent compound, and is among the most potent opioid agonists in this family, around 20 times stronger than fentanyl. It has become an increasingly widespread drug of abuse in its own right, linked to numerous cases of drug overdose,and may be considered an analog of a schedule 1 drug in the USA. On October 25th an intent to temporarily schedule Etonitazepipne and N-desethyl Isotonitazene was published.So on November 24th a month after publishing intent, it will most likely be placed in schedule 1.
N-Desethyletonitazene is a benzimidazole derivative with potent opioid effects which has been sold as a designer drug. It is better known as an active metabolite of the related compound etonitazene, but has similar activity to the parent compound and has sometimes appeared as a drug of abuse in its own right.
Utopioids are a class of synthetic opioid analgesic drugs first developed in the 1970s by the pharmaceutical company Upjohn, but never marketed for medical use, although some compounds from this class have been used for scientific research as model kappa opioid receptor agonists. In the mid-2010s, one mu opioid receptor selective compound from this class, U-47700, re-emerged as a designer drug and became widely sold around the world for several years before being banned in various jurisdictions from 2016 onwards. Following the banning of U-47700, a number of related compounds have continued to appear on illicit drug markets, typically sold over the internet or as components of mixtures sold as "street heroin". U-47700 itself is the most potent mu opioid agonist from this class, around 7-10x the potency of morphine. Some other compounds such as 3,4-MDO-U-47700 and N-Ethyl-U-47700 retain similar mu selectivity but with lower potency similar to that of morphine, or have a mixture of mu and kappa mediated effects, such as U-48800. Most utopioid derivatives are however selective kappa agonists, which may have limited abuse potential as dissociative hallucinogens, but do not alleviate withdrawal distress in opioid dependent individuals or maintain addiction in a typical sense. Nevertheless, this has not stopped them from being sold as designer drugs, and a number of these compounds are now banned in many jurisdictions alongside U-47700 itself.
Etoetonitazene is a benzimidazole derivative with opioid effects, first developed in the 1950s as part of the research that led to better-known compounds such as etonitazene. It is an analogue of etonitazene where the ethoxy group has been extended to ethoxyethoxy. It is less potent than etonitazene itself, but is still a potent opioid agonist with around 50x the potency of morphine, and has been sold as a designer drug since around 2022.
Flunitazene (Fluonitazene) is a benzimidazole derivative with opioid effects, first developed in the 1950s as part of the research that led to better-known compounds such as etonitazene. It is one of the least potent derivatives from this class to have appeared as a designer drug, with only around the same potency as morphine, but nevertheless has been sold since around 2020, and has been linked to numerous drug overdose cases.
