1-(M-CHLOROPHENYL)-BIGUANIDE, A POTENT HIGH-AFFINITY 5-HT3 RECEPTOR AGONIST

被引:175
作者
KILPATRICK, GJ [1 ]
BUTLER, A [1 ]
BURRIDGE, J [1 ]
OXFORD, AW [1 ]
机构
[1] GLAXO GRP RES LTD,DIV CLIN RES,WARE SG12 0DP,HERTS,ENGLAND
关键词
2-Methyl-5-HT; 5-HT[!sub]3[!/sub] receptor agonists; 5-HT[!sub]3[!/sub] receptors; mCPBG (1-(m-chlorophenyl)-biguanide); Phenylbiguanide;
D O I
10.1016/0014-2999(90)90513-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1-(m-Chlorophenyl)-biguanide (mCPBG) was examined and compared with three 5-HT3 receptor agonists in three 5-HT3 receptor models. mCPBG inhibited [3H]GR67330 binding to 5-HT3 receptors with high affinity (IC50 1.5 nM). mCPBG depolarized the rat vagus nerve with an EC50 one tenth of that for 5-HT (0.05 vs. 0.46 μM); the maximum depolarization was approximately half that for 5-HT. The mCPBG depolarization was potently blocked by the selective 5-HT3 antagonist, ondansetron (pKB 8.6 ± 0.1). In anaesthetised cats, mCPBG potently evoked the Bezold- Jarisch reflex which was blocked by low doses of ondansetron (10 μg/kg i.v.). It is concluded that mCPBG is a potent, high affinity 5-HT3 receptor agonist. © 1990.
引用
收藏
页码:193 / 197
页数:5
相关论文
共 10 条
[1]   PHARMACOLOGICAL PROPERTIES OF GR38032F, A NOVEL ANTAGONIST AT 5-HT3 RECEPTORS [J].
BUTLER, A ;
HILL, JM ;
IRELAND, SJ ;
JORDAN, CC ;
TYERS, MB .
BRITISH JOURNAL OF PHARMACOLOGY, 1988, 94 (02) :397-412
[2]   IDENTITY OF INHIBITORY PRESYNAPTIC 5-HYDROXYTRYPTAMINE (5-HT) AUTORECEPTORS IN THE RAT-BRAIN CORTEX WITH 5-HT1B BINDING-SITES [J].
ENGEL, G ;
GOTHERT, M ;
HOYER, D ;
SCHLICKER, E ;
HILLENBRAND, K .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1986, 332 (01) :1-7
[3]   PHARMACOLOGICAL PROPERTIES OF PHENYLDIGUANIDE AND OTHER AMIDINE DERIVATIVES IN RELATION TO THOSE OF 5-HYDROXYTRYPTAMINE [J].
FASTIER, FN ;
MCDOWALL, MA ;
WAAL, H .
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1959, 14 (04) :527-535
[5]   PHARMACOLOGICAL CHARACTERIZATION OF 5-HYDROXYTRYPTAMINE-INDUCED DEPOLARIZATION OF THE RAT ISOLATED VAGUS NERVE [J].
IRELAND, SJ ;
TYERS, MB .
BRITISH JOURNAL OF PHARMACOLOGY, 1987, 90 (01) :229-238
[6]  
KILPATRICK G J, 1989, British Journal of Pharmacology, V96, p8P
[7]   IDENTIFICATION AND DISTRIBUTION OF 5-HT3 RECEPTORS IN RAT-BRAIN USING RADIOLIGAND BINDING [J].
KILPATRICK, GJ ;
JONES, BJ ;
TYERS, MB .
NATURE, 1987, 330 (6150) :746-748
[8]   IDENTIFICATION OF SEROTONIN M-RECEPTOR SUBTYPES AND THEIR SPECIFIC BLOCKADE BY A NEW CLASS OF DRUGS [J].
RICHARDSON, BP ;
ENGEL, G ;
DONATSCH, P ;
STADLER, PA .
NATURE, 1985, 316 (6024) :126-131
[9]   THE PUTATIVE 5-HT3 AGONIST PHENYLBIGUANIDE INDUCES CARRIER-MEDIATED RELEASE OF [H-3]DOPAMINE [J].
SCHMIDT, CJ ;
BLACK, CK .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 167 (02) :309-310
[10]   RELATIVE ACTIVITIES OF SUBSTANCES RELATED TO 5-HYDROXYTRYPTAMINE AS DEPOLARIZING AGENTS OF SUPERIOR CERVICAL-GANGLION CELLS [J].
WALLIS, D ;
NASH, H .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1981, 70 (03) :381-392