Pharmacological profiles in rats of novel antipsychotics with combined dopamine D2/serotonin 5-HT1A activity:: comparison with typical and atypical conventional antipsychotics

被引:46
作者
Bardin, Laurent [1 ]
Auclair, Agnes [1 ]
Kleven, Mark S. [1 ]
Prinssen, Eric P. M. [1 ]
Koek, Wouter [1 ]
Newman-Tancredi, Adrian [1 ]
Depoortre, Ronan [1 ]
机构
[1] Ctr Rech Pierre Fabre, Div Neurobiol 2, F-81106 Castres, France
来源
BEHAVIOURAL PHARMACOLOGY | 2007年 / 18卷 / 02期
关键词
antipsychotics; catalepsy; conditioned avoidance response; D-amphetamine; dopamine D-2 receptors; 5-HT1A receptors; methylphenidate; rat;
D O I
10.1097/FBP.0b013e3280ae6c96
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Combining antagonist/partial agonist activity at dopamine D-2 and agonist activity at serotonin 5-HT1A receptors is one of the approaches that has recently been chosen to develop new generation antipsychotics, including bifeprunox, SSR181507 and SLV313. There have been, however, few comparative data on their pharmacological profiles. Here, we have directly compared a wide array of these novel dopamine D-2/5-HT1A and conventional antipsychotics in rat models predictive of antipsychotic activity. Potency of antipsychotics to antagonize conditioned avoidance, methylphenidate-induced behaviour and D-amphetamine-induced hyperlocomotion correlated with their affinity at dopamine D-2 receptors. Potency against ketamine-induced hyperlocomotion was independent of affinity at dopamine D-2 or 5-HT1A receptors. Propensity to induce catalepsy, predictive of occurrence of extrapyramidal side effects, was inversely related to affinity at 5-HT1A receptors. As a result, preferential D2/5-HT1A antipsychotics displayed a large separation between doses producing 'antipsychotic-like' vs. cataleptogenic actions. These data support the contention that 5-HT1A receptor activation greatly reduces or prevents the cataleptogenic potential of novel antipsychotics. They also emphasize that interactions at 5-HT1A and D-2 receptors, and the nature of effects (antagonism or partial agonism) at the latter has a profound influence on pharmacological activities, and is likely to affect therapeutic profiles.
引用
收藏
页码:103 / 118
页数:16
相关论文
共 74 条
[1]  
ARNT J, 1982, ACTA PHARMACOL TOX, V51, P321
[2]   DIFFERENTIAL-EFFECTS OF CLASSICAL AND NEWER ANTIPSYCHOTICS ON THE HYPERMOTILITY INDUCED BY 2 DOSE LEVELS OF D-AMPHETAMINE [J].
ARNT, J .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 283 (1-3) :55-62
[3]   In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles [J].
Assie, Marie-Bernadette ;
Dominguez, Helene ;
Consul-Denjean, Nathalie ;
Newman-Tancredi, Adrian .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2006, 373 (06) :441-450
[4]   5-HT1A receptor agonist properties of the antipsychotic, nemonapride: comparison with bromerguride and clozapine [J].
Assie, MB ;
Cosi, C ;
Koek, W .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 334 (2-3) :141-147
[5]  
AUCLAIR A, 2006, INT J NEUROPSYCHO S1, V9
[6]   A positron emission tomography study of the 5-HT1A receptor in schizophrenia and during clozapine treatment [J].
Bantick, RA ;
Montgomery, AJ ;
Bench, CJ ;
Choudhry, T ;
Malek, N ;
McKenna, PJ ;
Quested, DJ ;
Deakin, JFW ;
Grasby, PM .
JOURNAL OF PSYCHOPHARMACOLOGY, 2004, 18 (03) :346-354
[7]   The 5-HT1A receptor in schizophrenia:: a promising target for novel atypical neuroleptics? [J].
Bantick, RA ;
Deakin, JFW ;
Grasby, PM .
JOURNAL OF PSYCHOPHARMACOLOGY, 2001, 15 (01) :37-46
[8]  
BANTICK RA, 2000, J PSYCHOPHARMACOL S, V14, pPG20
[9]   Obesity and related metabolic abnormalities during antipsychotic drug administration: Mechanisms, management and research perspectives [J].
Baptista, T ;
Kin, NMKNY ;
Beaulieu, S ;
de Baptista, EA .
PHARMACOPSYCHIATRY, 2002, 35 (06) :205-219
[10]   Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties [J].
Bardin, Laurent ;
Kleven, Mark S. ;
Barret-Grevoz, Catherine ;
Depoortere, Ronan ;
Newman-Tancredi, Adrian .
NEUROPSYCHOPHARMACOLOGY, 2006, 31 (09) :1869-1879