EMD 281014, a new selective serotonin 5-HT2A receptor antagonist

被引：34

作者：

Bartoszyk, GD ^{[1
]}

van Amsterdam, C ^{[1
]}

Böttcher, H ^{[1
]}

Seyfried, CA ^{[1
]}

机构：

[1] Preclin Res Merck KGaA, Dept CNS Res, D-64271 Darmstadt, Germany

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2003年 / 473卷 / 2-3期

关键词：

5-HT2A receptor antagonist; EMD; 281014; M; 100907;

D O I：

10.1016/S0014-2999(03)01992-7

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The 5-HT2A receptor ligand 7-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-l-carbony}-1H-indole-3-carbonitrile HCl (EMD 281014) selectively binds to human (h) and rat 5-HT2A receptors (IC50 values 0.35 and 1 nM, respectively; vs. 1334 nM for h5-HT2C) and inhibited 5-HT-stimulated [S-35]guanosine 5'-O-3-thiotriphosphate (GTP-gammaS)-accumulation in h5-HT2A transfected Chinese hamster ovary cells (IC50 9.3 nM). EMD 281014 counteracted the N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced decrease of [H-3]ketanserin binding in rat frontal cortex (ID50 0.4 mg/kg p.o.) and R-(-)-1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI)-induced head-twitch behaviour in mice (ID50 0.01 mg/kg s.c., 0.06 mg/kg p.o.), demonstrating unique selectivity and efficacy. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：229 / 230

页数：2

共 9 条

[1] THE PHARMACOLOGY AND DISTRIBUTION OF HUMAN 5-HYDROXYTRYPTAMINE(2B) (5-HT2B) RECEPTOR GENE-PRODUCTS - COMPARISON WITH 5-HT2A AND 5-HT2C RECEPTORS [J].

BONHAUS, DW ;

BACH, C ;

DESOUZA, A ;

SALAZAR, FHR ;

MATSUOKA, BD ;

ZUPPAN, P ;

CHAN, HW ;

EGLEN, RM .

BRITISH JOURNAL OF PHARMACOLOGY, 1995, 115 (04) :622-628

[2] TEMPORAL DIFFERENTIAL ADAPTATION OF HEAD-TWITCH AND EAR-SCRATCH RESPONSES FOLLOWING ADMINISTRATION OF CHALLENGE DOSES OF DOI [J].

DARMANI, NA ;

GERDES, CF .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1995, 50 (04) :545-550

[3]

de Angelis Luisa, 2002, Curr Opin Investig Drugs, V3, P106

[4] Activation of mesolimbic dopamine function by phencyclidine is enhanced by 5-HT2C/2B receptor antagonists:: neurochemical and behavioural studies [J].

Hutson, PH ;

Barton, CL ;

Jay, M ;

Blurton, P ;

Burkamp, F ;

Clarkson, R ;

Bristow, LJ .

NEUROPHARMACOLOGY, 2000, 39 (12) :2318-2328

[5]

Kehne JH, 1996, J PHARMACOL EXP THER, V277, P968

[6] The effects of the peptide-coupling agent, EEDQ, on 5-HT2A receptor binding and function in rat frontal cortex [J].

Kettle, CJ ;

Cheetham, SC ;

Martin, KF ;

Prow, MR ;

Heal, DJ .

NEUROPHARMACOLOGY, 1999, 38 (09) :1421-1430

[7]

KLOCKOW M, 1986, ARZNEIMITTEL-FORSCH, V36-1, P197

[8] Inhibition of the constitutive activity of human 5-HT1A receptors by the inverse agonist, spiperone but not the neutral antagonist, WAY 100,635 [J].

NewmanTancredi, A ;

Conte, C ;

Chaput, C ;

Spedding, M ;

Millan, MJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1997, 120 (05) :737-739

[9]

OFFORD S, 1998, CINP P, P377

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