Carfentanil or carfentanyl, sold under the brand name Wildnil, is an extremely potent opioid analgesic which is used in veterinary medicine to anesthetize large animals such as elephants and rhinoceroses. It is typically administered in this context by tranquilizer dart. Carfentanil has also been used in humans for imaging of opioid receptors. It has additionally been used as a recreational drug, typically by injection, insufflation, or inhalation. Deaths have been reported in association with carfentanil.
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.
Lofentanil or lofentanyl is one of the most potent opioid analgesics known and is an analogue of fentanyl, which was developed in 1960. It is most similar to the highly potent opioid carfentanil (4-carbomethoxyfentanyl), only slightly more potent. Lofentanil can be described as 3-methylcarfentanil, or 3-methyl-4-carbomethoxyfentanyl. While 3-methylfentanyl is considerably more potent than fentanyl itself, lofentanil is only slightly stronger than carfentanil. This suggests that substitution at both the 3 and 4 positions of the piperidine ring introduces steric hindrance which prevents μ-opioid affinity from increasing much further. As with other 3-substituted fentanyl derivatives such as ohmefentanyl, the stereoisomerism of lofentanil is very important, with some stereoisomers being much more potent than others.
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.
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.
Butyrfentanyl or butyrylfentanyl is a potent short-acting synthetic opioid analgesic drug. It is an analog of fentanyl with around one quarter of its potency. One of the first mentions of this drug can be found in document written by The College on Problem of Drug Dependence, where it is mentioned as N-butyramide fentanyl analog. This document also states that the article describing its clinical effects was published in 1987. It is an agonist for the μ-opioid receptors.
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.
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.
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.
Etonitazene 5-acetyl analogue (Etoacetazene, 5-acetyldesnitroetonitazene) 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 5-nitro (NO2) group has been replaced by an acetyl (COCH3) group. It is described as having "reduced but still significant" potency compared to etonitazene itself. This compound was also tested as part of a series of cannabinoid receptor 2 agonists, and was found to be active though with fairly low potency of 960 nM at CB2, and negligible activity at CB1.
Etonitazene 5-cyano analogue (Etocyanazene, 5-cyanodesnitroetonitazene) 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 5-nitro (NO2) group has been replaced by a nitrile (C≡N) group. It is described as having "reduced but still significant" potency compared to etonitazene itself. It was made illegal in Germany in July 2021.
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.
Isotonitazepyne is a benzimidazole derivative with potent opioid effects, which has been sold as a designer drug over the internet. It was first detected in Russia in 2022, and has since been found around the world, tentatively identified in New Zealand in 2023 though it can be difficult to distinguish from the isomeric compound protonitazepyne. It is specifically listed as an illegal drug in the US state of Virginia.
