Park, WK Jeong, D Yun, CW Lee, S Cho, H Kim, GD Koh, HY Pae, AN Cho, YS Choi, KI Jung, JY Jung, SH Kong, JY 2024-01-21T08:01:35Z 2024-01-21T08:01:35Z 2021-09-03 2003-12 1043-6618 https://pubs.kist.re.kr/handle/201004/138054 1-(2-Ethoxy-phenyl)-4-[3-(3-thiophen-2-yl-isoxazolin-5-yl)-propyl]-piperazine (KCH-1110), has a high affinity for human dopamine D-3 (hD(3)) receptor (K-i = 1.28 nM) with about 90-fold selectivity over the human dopamine D-2L (hD(2L)) 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 D-3 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. (C) 2003 Elsevier Ltd. All rights reserved. English ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD WILD-TYPE MICE COMPETITIVE ANTAGONIST LOCOMOTOR-ACTIVITY CLIMBING BEHAVIOR PROLACTIN-RELEASE MOTOR-ACTIVITY HIGH-AFFINITY IN-VIVO RAT LOCALIZATION Pharmacological actions of a novel and selective dopamine D-3 receptor antagonist, KCH-1110 Article 10.1016/S1043-6618(03)00242-1 1 PHARMACOLOGICAL RESEARCH, v.48, no.6, pp.615 - 622 PHARMACOLOGICAL RESEARCH 48 6 615 622 scie scopus 000186621600011 2-s2.0-12144286144 Pharmacology & Pharmacy Pharmacology & Pharmacy Article WILD-TYPE MICE COMPETITIVE ANTAGONIST LOCOMOTOR-ACTIVITY CLIMBING BEHAVIOR PROLACTIN-RELEASE MOTOR-ACTIVITY HIGH-AFFINITY IN-VIVO RAT LOCALIZATION KCH-1110 D-3 antagonist antipsychotics