# 25CN-NBOH

25CN-NBOH (sometimes also referred to as NBOH-2C-CN) is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. It is a member of the NBOMe family of psychedelics.
The drug is notable in being one of the most selective agonists of the serotonin 5-HT$_{2A}$ receptor known.
A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to serotonin 5-HT$_2$ receptors and autoradiography.

## Pharmacology
### Pharmacodynamics
#### Actions

25CN-NBOH is notable as one of the most selective agonists of the serotonin 5-HT$_{2A}$ receptor yet discovered, with an affinity (pK$_i$) of 8.88 at the human serotonin 5-HT$_{2A}$ receptor, 100-fold selectivity for the serotonin 5-HT$_{2A}$ receptor over the serotonin 5-HT$_{2C}$ receptor, and 46-fold selectivity for the serotonin 5-HT$_{2A}$ receptor over the serotonin 5-HT$_{2B}$ receptor. However, another study found that 25CN-NBOH only had around 25-fold selectivity for the serotonin 5-HT$_{2A}$ receptor over the serotonin 5-HT$_{2B}$ and 5-HT$_{2C}$ receptors. In any case, in 2020, 25CN-NBOH and the related drug (S,S)-DMBMPP were described as the most selective serotonin 5-HT$_{2A}$ receptor agonists discovered to date.

#### Effects

25CN-NBOH was found to partially substitute for DOI in drug discrimination tests but was considerably weaker at inducing the head-twitch response (HTR) in mice. As with DOI, 25CN-NBOH has shown a biphasic or inverted U-shaped dose–response curve in terms of HTR induction. In addition, as with many other psychedelics, tolerance and tachyphylaxis develop to the HTR induced by 25CN-NBOH. A study of 25CN-NBOH concluded that "Given its distinct in vitro selectivity for 5-HT$_{2A}$ over non 5-HT$_2$ receptors and its behavioral dynamics, 25CN-NBOH appears to be a powerful tool for dissection of receptor-specific cortical circuit dynamics, including 5-HT$_{2A}$ related psychoactivity."
25CN-NBOH induces the HTRs also referred to as "wet dog shakes" (WDS) in rodents and the cortical fingerprint of serotonin-2A-receptor-mediated shaking behavior has been investigated in detail.
Additional in vivo investigations with this ligand has emerged. Chronic administration in mice lead to desensitization of the 5-HT2AR (measured via HTR) and increased startle amplitude whereas it does not effect reversal learning in mice. 25CN-NBOH was shown to increase the production of CTGF in chondrocytes. In rats, 25CN-NBOH induce a reduction in conditioned fear that was countered by pretreatment with 5-HT2AR inverse agonist MDL100907.

## Chemistry
### Structure

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.

### Synthesis

25CN-NBOH is readily available from 2C-H in 57% over 4 steps.

### Detection

A bioanalytical method for the detection of 25CN-NBOH has been developed.

## Literature

A review covering the literature up to 2020 was published in 2021.

## Related compounds

The tendency of the 4-cyano substitution to confer high 5-HT$_{2A}$ selectivity had previously been observed with DOCN, but this was not sufficiently potent to be widely adopted as a research ligand. 25CN-NBOH is still slightly less selective for 5-HT$_{2A}$ than the more complex cyclized derivative 2S,6S-DMBMPP ((2S,6S)-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine), in binding assays, however it is also less complex to synthesize and has higher efficacy and selectivity in functional assays as a partial agonist of the 5-HT$_{2A}$ receptor.

## Legality
### Hungary

25CN-NBOH is illegal in Hungary.

### United Kingdom

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.