Ro60-0175

Ro60-0175, or Ro-600175, also known as (S)-5-fluoro-6-chloro-α-methylisotryptamine ((S)-5-F-6-Cl-isoAMT), is a serotonin 5-HT2 receptor agonist of the isotryptamine family developed by Hoffmann–La Roche, which has applications in scientific research. It is the enantiopure (S)- isomer of the 5-fluoro and 6-chloro derivative of α-methylisotryptamine (isoAMT).

It acts as a potent and selective agonist of both the serotonin 5-HT2B and 5-HT2C receptor subtypes, with good selectivity over the closely related serotonin 5-HT2A subtype, and little or no affinity at other receptors. However, Ro60-0175 also activates the serotonin 5-HT2A receptor less potently than the serotonin 5-HT2B and 5-HT2C receptors. Its EC50Tooltip half-maximal effective concentration and EmaxTooltip maximal efficacy values have been found to be 0.91–2.4 nM (79–130%) at the serotonin 5-HT2B receptor, 32–52 nM (84–88%) at the serotonin 5-HT2C receptor, and 400–447 nM (69–91%) at the serotonin 5-HT2A receptor.

The drug has been found to produce hypolocomotion and sedative-like effects, antidepressant-like effects, anxiolytic-like effects or no change in anxiety-like responses, anti-obsessive-like effects, antipsychotic-like effects, appetite suppression, and penile erections in rodent animal studies. It fully generalizes with the preferential serotonin 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in rodent drug discrimination tests, which can be blocked by the selective serotonin 5-HT2C receptor antagonist SB-242084. Ro60-0175 also generalizes with the selective serotonin reuptake inhibitor (SSRI) citalopram in rodent drug discrimination tests, which can likewise be blocked by SB-242084, suggesting a major role for the serotonin 5-HT2C receptor in the interoceptive effects of SSRIs. The drug has been found to inhibit dopaminergic signaling in the mesolimbic pathway.

Ro60-0175 does not induce the head-twitch response, a behavioral proxy of psychedelic effects, when administered alone in rodents.