Biscaline

Biscaline, also known as 3,5-dimethoxy-4-phenylphenethylamine, is a monoamine receptor modulator of the phenethylamine family. It is the analogue of mescaline (3,4,5-dimethoxyphenethylamine) in which the methoxy group at the 4 position has been replaced with a phenyl ring.

The drug shows affinity for the serotonin 5-HT_1A receptor (K_i = 4,021 nM). Conversely, it did not bind to the serotonin 5-HT_2A, 5-HT_2B, or 5-HT_2C receptors at the assessed concentrations (K_i = >13,400 nM, >10,000 nM, and >14,590 nM, respectively). It is said to have lacked activational effects on the serotonin 5-HT_2A and 5-HT_2B receptors at the assessed concentrations. Biscaline also bound to the α_2A-adrenergic receptor (K_i = 797 nM), but not to the α_1A-adrenergic receptor, the dopamine D₂ receptor, or the monoamine transporters (SERTTooltip serotonin transporter, NETTooltip norepinephrine transporter, or DATTooltip dopamine transporter) at the assessed concentrations (K_i = >7,510–10,550 nM). It was a very weak monoamine reuptake inhibitor, with IC₅₀Tooltip half-maximal inhibitory concentration values of 457,000 nM for serotonin, 160,000 nM for norepinephrine, and 573,000 nM for dopamine.

Besides the monoamine receptors and transporters, biscaline showed affinity for the rat trace amine-associated receptor 1 (TAAR1) (K_i = 586 nM), but not for the mouse TAAR1 (K_i = >4,270 nM) and did not activate the human TAAR1 (EC₅₀Tooltip half-maximal effective concentration = >30,000 nM). Biscaline's interaction with the α_2A-adrenergic receptor may be the only significant human pharmacological interaction detected with the compound so far. Due to its lack of activation of the serotonin 5-HT_2A receptor, biscaline would not be expected to produce psychedelic effects.

A variety of 2C analogues and derivatives of biscaline have been synthesized and studied, such as 2C-Ph (2C-BI-1).