Description
Ro 60-0175 is an agonist of the serotonin (5-HT) receptor subtype 5-HT2 that stimulates increases in intracellular calcium levels in CHO-K1 cells expressing human 5-HT2A, 5-HT2B, and 5-HT2C receptors (EC50s = 447, 0.9, and 32 nM, respectively). It is selective for human 5-HT2A and 5-HT2C (Kis = 32 and 1 nM, respectively) over human 5-HT1A, 5-HT1D, 5-HT6, and 5-HT7, rat 5-HT1B and 5-HT3, and guinea pig 5-HT4 receptors (Kis = ≥1,995 nM), as well as adenosine A1 and A2, histamine H1-3, dopamine D1-5, α1-, α2-, and β1-adrenergic, M1-5 muscarinic, nicotinic, kainate, AMPA, and μ-, δ-, and κ-opioid receptors (IC50s = >1,000 nM), but does bind to β2-adrenergic receptors (IC50 = 251 nM). In vivo, Ro 60-0175 increases plasma levels of corticosterone, oxytocin, and prolactin in rats (ED50s = 2.43, 4.19, and 4.03 mg/kg, respectively), effects that are not inhibited by the 5-HT2C antagonist SB-242084 or the 5-HT2A antagonist MDL 100,907 (volinanserin; ).
Biological Activity
Potent, selective 5-HT 2 receptor agonist; shows selectivity for the 5-HT 2C subtype (pK i values are 9, 7.5, 5.4, 5.2 and 5.6 for human 5-HT 2C , 2A , 1A , 6 and 7 receptors respectively). Centrally active following oral or systemic administration in vivo .
References
[1] R H P PORTER. Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells[J]. British Journal of Pharmacology, 2009, 128 1: 13-20. DOI:
10.1038/sj.bjp.0702751[2] J R MARTIN. 5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential.[J]. Journal of Pharmacology and Experimental Therapeutics, 1998, 286 2: 913-924.
[3] K J DAMJANOSKA. 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.[J]. Journal of Pharmacology and Experimental Therapeutics, 2003, 304 3: 1209-1216. DOI:
10.1124/jpet.102.043489
