Preclinical research into cognition enhancers

被引:43
作者
Sarter, Martin [1 ]
机构
[1] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA
关键词
D O I
10.1016/j.tips.2006.09.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The preclinicall development of drugs to treat the cognitive symptoms of neuropsychiatric and neurological disorders is a formidable challenge. Evidence from a wide range of preclinical behavioral and neuropharmacologicall tests has formed the basis for predicting drug-induced cognition enhancement in normal volunteers and in patients with cognitive impairments. However, the limited validity of preclinical predictions of this enhancement in humans indicates that conventional screening for 'broadly active' compounds represents a below-optimal research strategy. This article conceptualizes the evidence needed to improve the predictive validity of preclinical research designed to discover and characterize cognition enhancers. We suggest that the investigation of reciprocal relationships among molecular, cellular, behavioral and cognitive processes modulated by candidate drugs represents the core of such research. By contrast, the usefulness of simple and high-throughput screening tests for the detection of cognition enhancers might be restricted to advanced drug-finding programs that are guided by evidence of the modulation of neurocognitive relationships by cognition enhancers and that are informed by iterative preclinical-clinical cross-validation of research approaches. We stress the need for basic biopsychollogicall research approaches in preclinical programs to find and characterize drugs to treat cognitive disorders.
引用
收藏
页码:602 / 608
页数:7
相关论文
共 44 条
[1]  
ARNERIC SP, 1994, J PHARMACOL EXP THER, V270, P310
[2]   Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory [J].
Bentley, P ;
Husain, M ;
Dolan, RJ .
NEURON, 2004, 41 (06) :969-982
[3]   IMPROVEMENT IN PERFORMANCE OF A DELAYED MATCHING-TO-SAMPLE TASK BY MONKEYS FOLLOWING ABT-418 - A NOVEL CHOLINERGIC CHANNEL ACTIVATOR FOR MEMORY ENHANCEMENT [J].
BUCCAFUSCO, JJ ;
JACKSON, WJ ;
TERRY, AV ;
MARSH, KC ;
DECKER, MW ;
ARNERIC, SP .
PSYCHOPHARMACOLOGY, 1995, 120 (03) :256-266
[4]   A summary of the FDA-NIMH-MATRICS Workshop on Clinical Trial Design for Neurocognitive Drugs for Schizophrenia. [J].
Buchanan, RW ;
Davis, M ;
Goff, D ;
Green, MF ;
Keefe, RSE ;
Leon, AC ;
Nuechterlein, KH ;
Laughren, T ;
Levin, R ;
Stover, E ;
Fenton, W ;
Marder, SR .
SCHIZOPHRENIA BULLETIN, 2005, 31 (01) :5-19
[5]  
Decker MW, 1995, CRIT REV NEUROBIOL, V9, P321
[6]  
DECKER MW, 1994, J PHARMACOL EXP THER, V270, P319
[7]   Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia [J].
Floresco, SB ;
Geyer, MA ;
Gold, LH ;
Grace, AA .
SCHIZOPHRENIA BULLETIN, 2005, 31 (04) :888-894
[8]   NICOTINIC AND MUSCARINIC RECEPTORS IN THE RAT PREFRONTAL CORTEX - DIFFERENTIAL ROLES IN WORKING-MEMORY, RESPONSE SELECTION AND EFFORTFUL PROCESSING [J].
GRANON, S ;
POUCET, B ;
THINUSBLANC, C ;
CHANGEUX, JP ;
VIDAL, C .
PSYCHOPHARMACOLOGY, 1995, 119 (02) :139-144
[9]   Predicting drug efficacy for cognitive deficits in schizophrenia [J].
Hagan, JJ ;
Jones, DNC .
SCHIZOPHRENIA BULLETIN, 2005, 31 (04) :830-853
[10]   Attentional effects of nicotinic agonists in rats [J].
Hahn, B ;
Sharples, CGV ;
Wonnacott, S ;
Shoaib, M ;
Stolerman, P .
NEUROPHARMACOLOGY, 2003, 44 (08) :1054-1067