Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals.
Gray death is a slang term which refers to a potent mixture of synthetic opioids, for example benzimidazole opioids or fentanyl analogues, often sold on the street misleadingly as "heroin". However, other substances such as cocaine have also been laced with opioids that resulted in illness and death.
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.
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.
Metonitazene is an analgesic compound related to etonitazene, which was first reported in 1957, and has been shown to have approximately 1000 times the potency of morphine by central routes of administration, but if used orally it has been shown to have approximately 10 times the potency of morphine.
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.
Etonitazepyne is a benzimidazole derivative with potent opioid effects which has been sold over the internet as a designer drug and linked to numerous cases of overdose.
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.
Etomethazene (5-methyldesnitroetonitazene) is a benzimidazole derivative with opioid effects which has been sold as a designer drug over the internet since early 2022. It is an analogue of etonitazene where the nitro (NO2) group has been replaced by a methyl (CH3) group. While formal studies into its pharmacology have yet to be carried out, it showed far less potency than etonitazene itself. Etomethazene has a potency around 20 times than morphine with a relatively short duration about 30-100 min.
Protonitazepyne is a benzimidazole derivative with opioid effects, which has been sold as a designer drug over the internet, first being mentioned in mid 2022 and definitively identified in drug seizures in Canada in early 2023. It is an analogue of etonitazene where the ethoxy group has been extended to propoxy, and the N,N-diethyl substitution has been cyclised into a pyrrolidine ring. While formal studies into its pharmacology have yet to be carried out, it is believed to be slightly less potent than the ethoxy analogue etonitazepyne but still a potent opioid.
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.
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.
