Psychopharmacology

, Volume 136, Issue 2, pp 99–104

Deramciclane, a putative anxiolytic drug, is a serotonin 5-HT2C receptor inverse agonist but fails to induce 5-HT2C receptor down-regulation

Authors

  • E.-P. Pälvimäki
    • Department of Pharmacology and Clinical Pharmacology, University of Turku School of Medicine, Kiinamyllynkatu 10, FIN-20500 Turku, Finland Fax: +358-2-333-7216, e-mail: eepee@utu.fi
  • Hannu Majasuo
    • Department of Pharmacology and Clinical Pharmacology, University of Turku School of Medicine, Kiinamyllynkatu 10, FIN-20500 Turku, Finland Fax: +358-2-333-7216, e-mail: eepee@utu.fi
  • Mikko Kuoppamäki
    • Department of Pharmacology and Clinical Pharmacology, University of Turku School of Medicine, Kiinamyllynkatu 10, FIN-20500 Turku, Finland Fax: +358-2-333-7216, e-mail: eepee@utu.fi
  • Pekka T. Männistö
    • Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, FIN-70200 Kuopio, Finland
  • Erkka Syvälahti
    • Department of Pharmacology and Clinical Pharmacology, University of Turku School of Medicine, Kiinamyllynkatu 10, FIN-20500 Turku, Finland Fax: +358-2-333-7216, e-mail: eepee@utu.fi
  • Jarmo Hietala
    • Department of Psychiatry, University of Turku School of Medicine, Kiinamyllynkatu 10, FIN-20500 Turku, Finland
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130050544

Cite this article as:
Pälvimäki, E., Majasuo, H., Kuoppamäki, M. et al. Psychopharmacology (1998) 136: 99. doi:10.1007/s002130050544

Abstract

 Deramciclane (EGIS-3886) is a novel anxiolytic agent that binds with high affinity to 5-HT2A/2C receptors. The interactions of deramciclane with the serotonin 5-HT2C receptor were characterized further using receptor phosphoinositide hydrolysis assays and receptor autoradiography. Deramciclane antagonized 5-HT2C receptor mediated 5-HT-stimulated phosphoinositide hydrolysis with an IC50 value of 168 nM. Deramciclane also decreased basal phosphoinositide hydrolysis by up to 33% (EC50 = 93 nM) in a physiological system in the choroid plexus, suggesting that deramciclane possesses inverse agonist properties at this receptor. Administration of single doses of 0.5 mg/kg and 10 mg/kg resulted in a maximal 5-HT2C receptor occupancy of up to 45% and 79%, respectively, in the choroid plexus. Chronic (14 days) treatment with 0.5 mg/kg or 10 mg/kg deramciclane did not alter [125I]DOI (agonist) or [3H]mesulergine (antagonist) binding to 5-HT2C receptors in the choroid plexus compared to saline-treated controls, as determined by quantitative receptor autoradiography. In comparison, the effects of deramciclane on 5-HT2A binding characteristics and receptor occupancy were also studied. Deramciclane treatment resulted in 5-HT2A receptor occupancy of up to 78%, but no significant effect of chronic treatment on 5-HT2A receptor agonist binding levels was found. In conclusion, these data indicate that deramciclane is a 5-HT2C receptor inverse agonist and occupies 5-HT2C receptors during treatment, and that chronic treatment with deramciclane does not lead to 5-HT2C receptor down-regulation.

Key words Deramciclane Anxiolytic drug 5HT2C 5HT2A Serotonin receptor Receptor regulation Inverse agonist

Copyright information

© Springer-Verlag Berlin Heidelberg 1998