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Chemical compound From Wikipedia, the free encyclopedia
25CN-NBOH (sometimes also referred to as NBOH-2C-CN)[1] is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen.[2] This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B.[3][4][5][6] A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.[7]
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Other names | NBOH-2C-CN |
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Formula | C18H20N2O3 |
Molar mass | 312.369 g·mol−1 |
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The structure of 25CN-NBOH in complex with an engineered Gαq heterotrimer of the 5-HT2AR has been determined by cryoelectron microscopy (cryo-EM), showing a distinct binding mode when compared to LSD.[8]
25CN-NBOH is readily available from 2C-H in 57% over 4 steps.[9]
25CN-NBOH was found to partially substitute for DOI but was considerably weaker at inducing a head-twitch response in mice.[10][11] Another in vivo evaluation of 25CN-NBOH concluded that "Given its distinct in vitro selectivity for 5-HT2A over non 5-HT2 receptors and its behavioral dynamics, 25CN-NBOH appears to be a powerful tool for dissection of receptor-specific cortical circuit dynamics, including 5-HT2A related psychoactivity."[12]
25CN-NBOH induces the Head Twitch Response (HTR) also refererred to as "wet dog shakes" in rodents and the cortical fingerprint of serotonin-2A-receptor-mediated shaking behavior has been investigated in detail.[13]
Additional in vivo investigations with this ligand has emerged.[14][15][16][17][18][19][20][21] Chronic administration in mice lead to desensitization of the 5-HT2AR (measured via HTR) and increased startle amplitude[22] whereas it does not effect reversal learning in mice.[23] 25CN-NBOH was shown to increase the production of CTGF in chondrocytes.[24] In rats, 25CN-NBOH induce a reduction in conditioned fear that was countered by pretreatment with 5-HT2AR inverse agonist MDL100907.[25]
A bioanalytical method for the detection of 25CN-NBOH has been developed.[26]
A review covering the literature up to 2020 was published in 2021.[27]
The tendency of the 4-cyano substitution to confer high 5-HT2A selectivity had previously been observed with DOCN,[28] but this was not sufficiently potent to be widely adopted as a research ligand. 25CN-NBOH is still slightly less selective for 5-HT2A than the more complex cyclised derivative 2S,6S-DMBMPP ((2S,6S)-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine),[29] in binding assays, however it is also less complex to synthesise and has higher efficacy and selectivity in functional assays as a partial agonist of the 5-HT2A receptor.
25CN-NBOH is illegal in Hungary.[30]
This substance is a Class A drug in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971.[31]
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