NNE1 also recognized as NNEI, MN-24, and AM-6527, is an indole-based synthetic cannabinoid, a molecular fusion of APICA and JWH-018. This compound acts as an agonist for cannabinoid receptors, boasting Ki values of 60.09 nM at CB1 and 45.298 nM at CB2, along with EC50 values of 9.481 nM at CB1 and 1.008 nM at CB2. Initially developed by Abbott, NNE1 exhibits a remarkable CB1 receptor pEC50 of 8.9, displaying approximately 80-fold selectivity over the related CB2 receptor. Notably, there is concern that metabolic hydrolysis of NNE1’s amide group may lead to the release of 1-naphthylamine, a recognized carcinogen. This concern arises from the known metabolic liberation of amantadine in the related compound APINACA, where amantadine is also an impurity. Consequently, NNE1 was temporarily classified as a class drug in New Zealand in 2012, aimed at preventing its use as an ingredient in then-legal synthetic cannabis products. Tragically, NNE1 was later linked to the death of an individual in Japan in 2014.
What is NNE1, and how does it relate to synthetic cannabinoids?
NNE1, also known as NNEI, MN-24, and AM-6527, is an indole-based synthetic cannabinoid. It is a molecular hybrid of APICA and JWH-018, two other synthetic cannabinoids. NNE1 is designed to act as an agonist for cannabinoid receptors in the body.
What are the Ki and EC50 values associated with NNE1?
NNE1 has Ki values of approximately 60.09 nM at the CB1 receptor and 45.298 nM at the CB2 receptor. Additionally, it displays EC50 values of roughly 9.481 nM at the CB1 receptor and 1.008 nM at the CB2 receptor. These values indicate its affinity and potency in interacting with these receptors.
Who invented NNE1, and what is its selectivity?
NNE1 was initially developed by Abbott. It exhibits a CB1 receptor pEC50 of 8.9, showcasing significant selectivity, approximately 80-fold, in favour of the CB1 receptor compared to the CB2 receptor.
Are there safety concerns associated with NNE1’s use?
Yes, there are safety concerns related to NNE1. There is a possibility that metabolic hydrolysis of NNE1’s amide group may release 1-naphthylamine, a known carcinogen. This concern arises from the metabolic liberation of amantadine in a related compound, APINACA, where amantadine is also present as an impurity.
Why was NNE1 temporarily classified as a class drug in New Zealand in 2012?
NNE1 was temporarily classified as a class drug in New Zealand in 2012 as a preventive measure to curb its use as an ingredient in synthetic cannabis products that were then legal. This classification aimed to address potential health and safety risks associated with NNE1.
Has NNE1 been linked to any fatalities or adverse events?
Yes, NNE1 was tragically associated with the death of an individual in Japan in 2014. This highlights the potential risks and dangers of its use.
References
Uchiyama N, Matsuda S, Kawamura M, Shimokawa Y, Kikura-Hanajiri R, Aritake K, et al. (October 2014). “Characterization of four new designer drugs, 5-chloro-NNEI, NNEI indazole analog, α-PHPP and α-POP, with 11 newly distributed designer drugs in illegal products”. Forensic Science International. 243: 1–13. doi:10.1016/j.forsciint.2014.03.013. PMID 24769262.
Gamage TF, Farquhar CE, Lefever TW, Marusich JA, Kevin RC, McGregor IS, et al. (May 2018). “Molecular and Behavioral Pharmacological Characterization of Abused Synthetic Cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA”. The Journal of Pharmacology and Experimental Therapeutics. 365 (2): 437–446. doi:10.1124/jpet.117.246983. PMC 5932312. PMID 29549157.
Blaazer AR, Lange JH, van der Neut MA, Mulder A, den Boon FS, Werkman TR, et al. (October 2011). “Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: design, synthesis, structure-activity relationships, physicochemical properties and biological activity”. European Journal of Medicinal Chemistry. 46 (10): 5086–98. doi:10.10.1016/j.ejmech.2011.08.021. PMID 21885167.
New Zealand Government Gazette, Notice Number 7051, 1 November 2012.
Sasaki C, Saito T, Shinozuka T, Irie W, Murakami C, Maeda K, et al. (January 2015). “A case of death caused by abuse of a synthetic cannabinoid N -1-naphthalenyl-1-pentyl-1H -indole-3-carboxamide”. Forensic Toxicology. 33 (1): 165–169. doi:10.10.1007/s11419-014-0246-5. S2CID 13524298.
