It acts as apotent andselectiveagonist of both theserotonin5-HT2B and5-HT2Creceptor subtypes, with good selectivity over the closely related serotonin5-HT2A subtype, and little or noaffinity 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.[6] ItsEC50Tooltip half-maximal effective concentration andEmaxTooltip maximal efficacy 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]
Ro60-0175 does not induce thehead-twitch response, a behavioral proxy ofpsychedelic effects, when administered alone in rodents.[17][6] In addition, it suppresses the head-twitch response induced by the psychedelic drug(R)-DOI.[18][19] However, incombination with the selective serotonin 5-HT2C receptorantagonistSB-242084, Ro60-0175 robustly induces the head-twitch response.[17][6] This effect is abolished by addition of the selective serotonin 5-HT2A receptor antagonistketanserin orvolinanserin.[6] The preceding findings suggest that Ro60-0175 may be aserotonergic psychedelic and may havehallucinogenic effects in humans at sufficiently high doses or in combination with a serotonin 5-HT2C receptor antagonist.[6]
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^Quarta D, Naylor CG, Stolerman IP (August 2007). "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.193 (3):391–402.doi:10.1007/s00213-007-0802-3.PMID17473916.S2CID21020653.
^Damjanoska KJ, Muma NA, Zhang Y, D'Souza DN, Garcia F, Carrasco GA, et al. (March 2003). "Neuroendocrine evidence that (S)-2-(chloro-5-fluoro-indol- l-yl)-1-methylethylamine fumarate (Ro 60-0175) is not a selective 5-hydroxytryptamine(2C) receptor agonist".The Journal of Pharmacology and Experimental Therapeutics.304 (3):1209–1216.doi:10.1124/jpet.102.043489.PMID12604698.S2CID23880629.
^abcdeVickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, et al. (2001). "Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists".Pharmacology, Biochemistry, and Behavior.69 (3–4):643–652.doi:10.1016/s0091-3057(01)00552-4.PMID11509227.
^abKennett G, Lightowler S, Trail B, Bright F, Bromidge S (January 2000). "Effects of RO 60 0175, a 5-HT(2C) receptor agonist, in three animal models of anxiety".European Journal of Pharmacology.387 (2):197–204.doi:10.1016/s0014-2999(99)00706-2.PMID10650160.
^abMoreau JL, Bös M, Jenck F, Martin JR, Mortas P, Wichmann J (August 1996). "5HT2C receptor agonists exhibit antidepressant-like properties in the anhedonia model of depression in rats".European Neuropsychopharmacology.6 (3):169–175.doi:10.1016/0924-977x(96)00015-6.PMID8880075.
^Jenck F, Moreau JL, Berendsen HH, Boes M, Broekkamp CL, Martin JR, et al. (August 1998). "Antiaversive effects of 5HT2C receptor agonists and fluoxetine in a model of panic-like anxiety in rats".European Neuropsychopharmacology.8 (3):161–168.doi:10.1016/s0924-977x(97)00055-2.PMID9716307.
^Clifton PG, Lee MD, Dourish CT (October 2000). "Similarities in the action of Ro 60-0175, a 5-HT2C receptor agonist and d-fenfluramine on feeding patterns in the rat".Psychopharmacology.152 (3):256–267.doi:10.1007/s002130000504.PMID11105935.
^Millan MJ, Peglion JL, Lavielle G, Perrin-Monneyron S (April 1997). "5-HT2C receptors mediate penile erections in rats: actions of novel and selective agonists and antagonists".European Journal of Pharmacology.325 (1):9–12.doi:10.1016/s0014-2999(97)89962-1.PMID9151932.
^Dekeyne A, Girardon S, Millan MJ (March 1999). "Discriminative stimulus properties of the novel serotonin (5-HT)2C receptor agonist, RO 60-0175: a pharmacological analysis".Neuropharmacology.38 (3):415–423.doi:10.1016/s0028-3908(98)00203-2.PMID10219979.
^Millan MJ, Girardon S, Dekeyne A (March 1999). "5-HT2C receptors are involved in the discriminative stimulus effects of citalopram in rats".Psychopharmacology.142 (4):432–434.doi:10.1007/s002130050910.PMID10229070.
^Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E (August 1999). "SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system".Neuropharmacology.38 (8):1195–1205.doi:10.1016/s0028-3908(99)00047-7.PMID10462132.
^Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E (May 2000). "Biochemical and electrophysiological evidence that RO 60-0175 inhibits mesolimbic dopaminergic function through serotonin(2C) receptors".Brain Research.865 (1):85–90.doi:10.1016/s0006-8993(00)02246-0.PMID10814735.
^abNilsson BM (July 2006). "5-Hydroxytryptamine 2C (5-HT2C) receptor agonists as potential antiobesity agents".Journal of Medicinal Chemistry.49 (14):4023–4034.doi:10.1021/jm058240i.PMID16821762.
