4-HO-NBnT

4-HO-NBnT, also known as 4-hydroxy-N-benzyltryptamine, is a serotonin receptor agonist and putative psychedelic drug of the tryptamine and 4-hydroxytryptamine families related to norpsilocin (4-HO-NMT).

It is a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A receptor. The drug produces psychedelic-like effects in animals.

4-HO-NBnT was first described in the scientific literature in 2024.

4-HO-NBnT is a potent ligand of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. Of a series of nine N-monoalkyl-4-hydroxytryptamines, it was the most potent agonist of the serotonin 5-HT2A and 5-HT2B receptors. In addition, it was second only to norpsilocin in terms of potency as an agonist of the serotonin 5-HT2C receptor. 4-HO-NBnT acts as a high-efficacy partial agonist of the serotonin 5-HT2A receptor, as a very weak partial agonist or antagonist of the serotonin 5-HT2B receptor, and as a full agonist of the serotonin 5-HT2C receptor. Its EC50Tooltip half-maximal effective concentration and EmaxTooltip maximal efficacy values were 2.9 nM (73%) at the serotonin 5-HT2A receptor, 4.9 nM (11%) at the serotonin 5-HT2B receptor, and 70.7 nM (91%) at the serotonin 5-HT2C receptor.

In addition to the serotonin 5-HT2 receptors, 4-HO-NBnT shows affinity for and potent partial agonism of other serotonin receptors, including the serotonin 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT7A receptors. In contrast to norpsilocin and psilocin, 4-HO-NBnT was inactive as a serotonin 5-HT1A receptor agonist. It also shows substantial affinity for sigma σ1 and σ2 receptors (Ki = 43.3 nM and 249 nM, respectively).

4-HO-NBnT produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. Its potency in inducing the head-twitch response is about 10-fold lower than that of psilocin (4-HO-DMT), but is of about the same maximal efficacy in terms of frequency of head twitches. The production of the head-twitch response with the drug is in contrast to norpsilocin, which does not cause this response even at very high doses. 4-HO-NBnT also produces hypolocomotion and hypothermia in rodents.

4-HO-NBnT, also known as 4-hydroxy-N-benzyltryptamine, is a substituted tryptamine and 4-hydroxytryptamine derivative. It is the 4-hydroxy derivative of N-benzyltryptamine and is related to the naturally occurrence norpsilocin (4-HO-NMT).

The calculated log P of 4-HO-NBnT is 2.93. This is far higher than for instance norpsilocin (4-HO-NMT), which had a calculated log P of 0.90.

The chemical synthesis of 4-HO-NBnT has been described.

Chemical structures of 4-HO-NET, 4-HO-NPT, 4-HO-NiPT, and 4-HO-NBnT.

Analogues of 4-HO-NBnT include norpsilocin (4-HO-NMT), 4-HO-NET, 4-HO-NPT, 4-HO-NiPT, 4-HO-NALT, 4-HO-NBT (4-HO-NnBT), 4-HO-NtBT, and 4-HO-NcHT, among others.

4-HO-NBnT was first described in the scientific literature by Alexander Sherwood and colleagues in 2024.

• Substituted tryptamine

• N-Benzyltryptamine

• 5-MeO-NBnT

• 5-MeO-NBOMeT

• 25-NB (NBOMe)

• 25B-NB (N-benzyl-2C-B)

• 4-HO-NBnT - Isomer Design