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.[1][2][3] It is the enantiopure (S)- isomer of the 5-fluoro and 6-chloro derivative of α-methylisotryptamine (isoAMT).[1]
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.[4][5] However, Ro60-0175 also activates the serotonin 5-HT2A receptor less potently than the serotonin 5-HT2B and 5-HT2C receptors. Its EC50 and Emax values have been found to be 0.91–2.4nM (79–130%) at the serotonin 5-HT2B receptor, 32–52nM (84–88%) at the serotonin 5-HT2C receptor, and 400–447nM (69–91%) at the serotonin 5-HT2A receptor.[1]
The drug has been found to produce hypolocomotion and sedative-like effects, antidepressant-like effects, anxiolytic-like effects[6] or no change in anxiety-like responses,[7][8] anti-obsessive-like effects,[8] antipsychotic-like effects,[8] appetite suppression,[9] and penile erections in rodent animal studies.[10] It fully generalizes with the preferential serotonin 5-HT2C receptor agonist
Ro60-0175 does not induce the head-twitch response, a behavioral proxy of psychedelic effects, when administered alone in rodents.[15][16] In addition, it suppresses the head-twitch response induced by the psychedelic drug (R)-DOI.[17][18] However, in combination with the selective serotonin 5-HT2C receptor antagonist SB-242084, Ro60-0175 robustly induces the head-twitch response.[15][16] This effect is abolished by addition of the selective serotonin 5-HT2A receptor antagonist ketanserin or volinanserin.[16]
The drug was first described in the scientific literature by 1996.[19] It was under development by Roche for the treatment of major depressive disorder (MDD), anxiety disorders, and obsessive–compulsive disorder (OCD), and reached the preclinical research stage of development, but development was discontinued in 1997.[20][21]
See also
- Substituted isotryptamine
- Substituted tryptamine § Related compounds
- AL-34662
- AL-38022A
- Ro60-0213
- VER-3323
- YM-348
External links
References
- Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists Bioorganic & Medicinal Chemistry, February 2008^
- The serotonin 2C receptor agonist Ro-60-0175 attenuates effects of nicotine in the five-choice serial reaction time task and in drug discrimination Psychopharmacology, August 2007^
- The 5-HT2C receptor agonist Ro60-0175 reduces cocaine self-administration and reinstatement induced by the stressor yohimbine, and contextual cues Neuropsychopharmacology, May 2008^