ANTAGONISM OF [H-3] ZACOPRIDE BINDING TO 5-HT3 RECOGNITION SITES BY ITS (R) AND (S) ENANTIOMERS

被引：35

作者：

PINKUS, LM

SARBIN, NS

GORDON, JC

MUNSON, HR

机构：

[1] AH ROBINS RES LABS,DEPT MOLEC BIOL,RICHMOND,VA 23261

[2] AH ROBINS RES LABS,DEPT CHEM RES,RICHMOND,VA 23261

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1990年 / 179卷 / 1-2期

关键词：

(Human); 5-HT[!sub]3[!/sub] receptors; Benzamides; Intestine (small); Stereoisomers; Vagus nerve; Zacopride;

D O I：

10.1016/0014-2999(90)90425-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

[3H]Zacopride exhibits high affinity (Kd ≤ 1 nM) for 5-HT3 binding sites (inhibited by ICS 205-930) in rabbit intestinal muscularis and vagus nerve, human jejunum, rat intestinal muscularis and rat brain cortex. Its binding was inhibited by several 5-HT3 antagonists that displayed similar rank orders of potency in the tissues examined. Zacorpride's (S) enantiomer was significantly more potent than its (R) enantiomer (21- to 42-fold in rabbit and human; 8- to 12-fold in rat) as an inhibitor of [3H]zacopride binding. These studies indicate that the utility of [3H]zacopride as a high affinity 5-HT3 ligand resides with the (S) enantiomer. © 1990.

引用

页码：231 / 235

页数：5

共 11 条

[1] ALPHIN RS, 1986, DIGEST DIS SCI, V31, P4825
[2] IDENTIFICATION AND CHARACTERIZATION OF 5-HYDROXYTRYPTAMINE3 RECOGNITION SITES IN HUMAN-BRAIN TISSUE
BARNES, JM
BARNES, NM
COSTALL, B
IRONSIDE, JW
NAYLOR, RJ
[J]. JOURNAL OF NEUROCHEMISTRY, 1989, 53 (06) : 1787 - 1793
[3] CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
[4] ZACOPRIDE - ANXIOLYTIC PROFILE IN RODENT AND PRIMATE MODELS OF ANXIETY
COSTALL, B
DOMENEY, AM
GERRARD, PA
KELLY, ME
NAYLOR, RJ
[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 1988, 40 (04) : 302 - 305
[5] DEMAIN I, 1989, J CHROMATOGR, V466, P415
[6] FINNEY DJ, 1964, STATISTICAL METHODS
[7] GORDON JC, 1989, J PHARMACOL EXP THER, V251, P962
[8] SPECIES VARIATIONS IN 5-HT3 RECOGNITION SITES LABELED BY H-3 QUIPAZINE IN THE CENTRAL NERVOUS-SYSTEM
PEROUTKA, SJ
[J]. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1988, 338 (05) : 472 - 475
[9] ASSOCIATION OF [H-3] ZACOPRIDE WITH 5-HT3 BINDING-SITES
PINKUS, LM
SARBIN, NS
BAREFOOT, DS
GORDON, JC
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 168 (03) : 355 - 362
[10] THE ANTIEMETIC PROFILE OF ZACOPRIDE
SMITH, WL
ALPHIN, RS
JACKSON, CB
SANCILIO, LF
[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 1989, 41 (02) : 101 - 105

← 1 2 →