Pharmacological actions of a novel and selective dopamine D3 receptor antagonist, KCH-1110

Woo Kyu Park, Daeyoung Jeong, Cheol Won Yun, Sunghou Lee, Heeyeong Cho, Gun Do Kim, Hun Yeong Koh, Ae Nim Pae, Yong Seo Cho, Kyung Il Choi, Ji Young Jung, Sun Ho Jung, Jae Yang Kong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

1-(2-Ethoxy-phenyl)-4-[3-(3-thiophen-2-yl-isoxazolin-5-yl)-propyl] -piperazine (KCH-1110), has a high affinity for human dopamine D3 (hD3) receptor (Ki=1.28nM) with about 90-fold selectivity over the human dopamine D2L (hD2L) receptor. Antipsychotic or antidopaminergic activity of KCH-1110 was investigated in the models for the positive symptoms of schizophrenia, apomorphine-induced climbing and cocaine-induced hyperlocomotion, in mice. Intraperitoneal (i.p.) or oral (p.o.) administration of KCH-1110 potently inhibited the apomorphine-induced cage climbing without any rotarod ataxia in mice. Cocaine-induced hyperactivity was also antagonised by KCH-1110. In addition, KCH-1110 attenuated the hypothermia induced by a selective dopamine D3 agonist, 7-OH-DPAT in mice. KCH-1110 did not induce catalepsy in mice, but at much higher doses only a slight catalepsy response was shown. Although high doses of KCH-1110 significantly enhanced serum prolactin secretion in rats, low dose of KCH-1110 did not increase prolactin levels in rats. The present studies, therefore, suggest that KCH-1110 is a potent and relatively selective dopamine D 3 receptor antagonist with antipsychotic actions.

Original languageEnglish
Pages (from-to)615-622
Number of pages8
JournalPharmacological Research
Volume48
Issue number6
DOIs
Publication statusPublished - 2003 Dec
Externally publishedYes

Keywords

  • Antipsychotics
  • D antagonist
  • KCH-1110

ASJC Scopus subject areas

  • Pharmacology

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