Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2C receptor

被引:167
作者
Palvimaki, EP
Roth, BL
Majasuo, H
Laakso, A
Kuoppamaki, M
Syvalahti, E
Hietala, J
机构
[1] CASE WESTERN RESERVE UNIV, DEPT PSYCHIAT, CLEVELAND, OH 44106 USA
[2] CASE WESTERN RESERVE UNIV, SCH MED, DEPT BIOCHEM, CLEVELAND, OH 44106 USA
[3] UNIV TURKU, CENT HOSP, DEPT PSYCHIAT, FIN-20520 TURKU, FINLAND
关键词
citalopram; fluoxetine; imipramine; antidepressants; serotonin 5-HT2C receptor; serotonin 5-HT2A receptor;
D O I
10.1007/BF02246453
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Interactions of the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine and its main metabolite norfluoxetine, and the tricyclic antidepressant (TCA) imipramine with the rat serotonin 5-HT2C receptor in a clonal cell line and in the rat choroid plexus were investigated by radioligand binding and phosphoinositide (PI) hydrolysis assays. For comparison, the affinities of a variety of other antidepressants of different chemical classes for the cloned rat 5-HT2C and 5-HT2A receptors were also determined by radioligand binding assays. Fluoxetine displayed relatively high affinity for the 5-HT2C receptor in the choroid plexus, with a K-i value for inhibition of [H-3]mesulergine binding of 55.4 nM. The K-i values for imipramine, norfluoxetine and citalopram were 136 nM, 203 nM, and 298 nM, respectively. Similar rank order of potency was detected in PI hydrolysis assays, which showed that these drugs are antagonists at the 5-HT2C receptor without exhibiting inverse agonist activity [H-3]Ketanserin (5-HT2A) binding assays revealed that the SSRIs fluoxetine, norfluoxetine and citalopram show 10- to 23-fold selectivity for the 5-HT2C receptor in vitro, whereas the TCA imipramine does not. Many other TCAs also had high to intermediate affinity for both 5-HT2A and 5-HT2C receptors. The present data provide evidence that fluoxetine, norfluoxetine and citalopram, along with many other antidepressant compounds, interact directly with the 5-HT2C receptor.
引用
收藏
页码:234 / 240
页数:7
相关论文
共 42 条
[1]  
ABRAMOWSKI D, 1995, J NEUROCHEM, V65, P782
[2]  
APPEL NM, 1990, J PHARMACOL EXP THER, V255, P843
[3]   FLUOXETINE - A REVIEW OF RECEPTOR AND FUNCTIONAL-EFFECTS AND THEIR CLINICAL IMPLICATIONS [J].
BEASLEY, CM ;
MASICA, DN ;
POTVIN, JH .
PSYCHOPHARMACOLOGY, 1992, 107 (01) :1-10
[4]   FLUOXETINE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES, AND THERAPEUTIC EFFICACY IN DEPRESSIVE-ILLNESS [J].
BENFIELD, P ;
HEEL, RC ;
LEWIS, SP .
DRUGS, 1986, 32 (06) :481-508
[5]   EFFECTS OF SHORT-TERM AND LONG-TERM ADMINISTRATION OF FLUOXETINE ON THE MONOAMINE CONTENT OF RAT-BRAIN [J].
CACCIA, S ;
FRACASSO, C ;
GARATTINI, S ;
GUISO, G ;
SARATI, S .
NEUROPHARMACOLOGY, 1992, 31 (04) :343-347
[6]   BINDING OF TYPICAL AND ATYPICAL ANTIPSYCHOTICS TO 5-HT1C AND 5-HT2 SITES - CLOZAPINE POTENTLY INTERACTS WITH 5-HT1C SITES [J].
CANTON, H ;
VERRIELE, L ;
COLPAERT, FC .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 191 (01) :93-96
[7]   [H-3] PAROXETINE BINDING IN RAT FRONTAL-CORTEX STRONGLY CORRELATES WITH [H-3] 5-HT UPTAKE - EFFECT OF ADMINISTRATION OF VARIOUS ANTIDEPRESSANT TREATMENTS [J].
CHEETHAM, SC ;
VIGGERS, JA ;
SLATER, NA ;
HEAL, DJ ;
BUCKETT, WR .
NEUROPHARMACOLOGY, 1993, 32 (08) :737-743
[8]   AGONIST-INDUCED PHOSPHOINOSITIDE HYDROLYSIS IN CHOROID-PLEXUS [J].
CONN, PJ ;
SANDERSBUSH, E .
JOURNAL OF NEUROCHEMISTRY, 1986, 47 (06) :1754-1760
[9]  
FABRE LF, 1985, CURR THER RES CLIN E, V37, P115
[10]   IMPORTANCE OF DURATION OF DRUG ACTION IN ANTAGONISM OF P-CHLOROAMPHETAMINE DEPLETION OF BRAIN-SEROTONIN - COMPARISON OF FLUOXETINE AND CHLORIMIPRAMINE [J].
FULLER, RW ;
SNODDY, HD ;
PERRY, KW ;
BYMASTER, FP ;
WONG, DT .
BIOCHEMICAL PHARMACOLOGY, 1978, 27 (02) :193-198