Sigma receptor ligands: Possible application as therapeutic drugs and as radiopharmaceuticals

被引:129
作者
Hashimoto, Kenji
Ishiwata, Kiichi
机构
[1] Tokyo Metropolitan Inst Gerontol, Positron Med Ctr, Tokyo 1730022, Japan
[2] Chiba Univ, Ctr Forens Mental Hlth, Div Clin Neurosci, Chiba, Japan
关键词
D O I
10.2174/138161206778559614
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Sigma receptors are classified into sigma, and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system. The characterization of these subtypes and the discovery of new specific sigma receptor ligands demonstrated that sigma receptors are novel targets for the therapeutic treatment of neuropsychiatric diseases (schizophrenia, depression, and cognition), brain ischemia, and cocaine addiction. Furthermore, imaging of sigma, receptors in the human brain using specific PET radioligands has started. In addition, the two sigma receptor subtypes are also expressed on tumor cells, where they could be of prognostic relevance. The ability of sigma2 receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca2+, and sphingolipids has promoted the development of sigma(2) receptor agonists as novel therapeutic drugs for treating cancer. Consequently, sigma(2) receptor ligands have been demonstrated to be potentially useful tumor imaging ligands. In this article, we focus on the sigma receptor ligands as therapeutic agents and as radiopharmaceuticals.
引用
收藏
页码:3857 / 3876
页数:20
相关论文
共 198 条
[1]   Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells [J].
Al-Nabulsi, I ;
Mach, RH ;
Wang, LM ;
Wallen, CA ;
Keng, PC ;
Sten, K ;
Childers, SR ;
Wheeler, KT .
BRITISH JOURNAL OF CANCER, 1999, 81 (06) :925-933
[2]   Sigma receptors and cancer: Possible involvement of ion channels [J].
Aydar, E ;
Palmer, CP ;
Djamgoz, MBA .
CANCER RESEARCH, 2004, 64 (15) :5029-5035
[3]  
BEM WT, 1991, CANCER RES, V51, P6558
[4]   SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo [J].
Berthois, Y ;
Bourrié, B ;
Galiègue, S ;
Vidal, H ;
Carayon, P ;
Martin, PM ;
Casellas, P .
BRITISH JOURNAL OF CANCER, 2003, 88 (03) :438-446
[5]   Potent σ1-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine modulates basal and N-methyl-D-aspartate evoked nitric oxide production in vivo [J].
Bhardwaj, A ;
Sawada, M ;
London, ED ;
Koehler, RC ;
Traystman, RJ ;
Kirsch, JR .
STROKE, 1998, 29 (11) :2404-2410
[6]  
BORISON RL, 1991, PSYCHOPHARMACOL BULL, V27, P103
[7]   [H-3]1,3-di(2-tolyl)guanidine and [H-3](+)pentazocine binding sites in the rat brain: Autoradiographic visualization of the putative sigma(1) and sigma(2) receptor subtypes [J].
Bouchard, P ;
Quirion, R .
NEUROSCIENCE, 1997, 76 (02) :467-477
[8]   A sigma ligand, SR 31747A, potently modulates staphylococcal enterotoxin B-induced cytokine production in mice [J].
Bourrie, B ;
Benoit, JM ;
Derocq, JM ;
Esclangon, M ;
Thomas, C ;
LeFur, G ;
Casellas, P .
IMMUNOLOGY, 1996, 88 (03) :389-393
[9]   CB-64D AND CB-184 - LIGANDS WITH HIGH SIGMA(2) RECEPTOR AFFINITY AND SUBTYPE SELECTIVITY [J].
BOWEN, WD ;
BERTHA, CM ;
VILNER, BJ ;
RICE, KC .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 278 (03) :257-260
[10]   EVIDENCE FOR A MULTI-SITE MODEL OF THE RAT-BRAIN SIGMA-RECEPTOR [J].
BOWEN, WD ;
HELLEWELL, SB ;
MCGARRY, KA .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 163 (2-3) :309-318