Neuroendocrine evidence that (S)-2-(chloro-5-fluoro-indol-/-yl)-1-methylethylamine fumarate (Ro 60-0175) is not a selective 5-hydroxytryptamine2C receptor agonist

K. J. Damjanoska, N. A. Muma, Y. Zhang, D. N. D'Souza, F. Garcia, G. A. Carrasco, G. H. Kindel, K. A. Haskins, M. Shankaran, B. R. Petersen, L. D. Van De Kar

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15 Scopus citations


The 5-hydroxytryptamine2A and 2C (5-HT2A and 5-HT2C) receptors are so closely related that selective agonists have not been developed until recently with the advent of (S)-2-(chloro-5- fluoro-indol-/-yl)-1-methylethylamine fumarate (Ro 60-0175), a putatively selective 5-HT2C receptor agonist. In the present study, Ro 60-0175 was used to analyze the importance of 5-HT2C receptors in hormone secretion. Injection of Ro 60-0175 (5 mg/kg s.c.) produced a maximum increase in plasma levels of adrenocorticotrophic hormone, oxytocin, and prolactin at 15 min postinjection and a maximum increase in plasma corticosterone levels at 60 min postinjection. Ro 60-0175-mediated increases in plasma hormone levels were dose-dependent (corticosterone ED50 2.43 mg/kg; oxytocin ED50 = 4.19 mg/kg; and prolactin ED50 4.03 mg/kg). To assess the role of 5-HT2C and 5-HT2A receptors in mediating the hormone responses to Ro 60-0175, rats were pretreated with the 5-HT2C antagonist 6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbonyl] indoline (SB 242084) or 5-HT2A antagonists (±)-2,3-dimethoxyphenyl-1-[2-4-(piperidine)-methanol) (MDL 100,907) before injection of Ro 60-0175 (5 mg/kg s.c.). Neither SB 242084 (0.1, 0.5, 1, and 5 mg/kg i.p.) nor MDL 100,907 (1, 5, and 10 μg/kg s.c.) significantly inhibited the Ro 60-0175- induced increases in plasma hormone levels. The data suggest that Ro 60-0175 increases hormone secretion by mechanisms independent of the activation of 5-HT2C and/or 5-HT2A receptors and suggest that Ro 60-0175 is not a highly selective 5-HT2C receptor agonist.

Original languageEnglish (US)
Pages (from-to)1209-1216
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - Mar 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology


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