5-HT6 receptors as emerging targets for drug discovery

被引：79

作者：

Branchek, TA ^{[1
]}

Blackburn, TP ^{[1
]}

机构：

[1] Synapt Pharmaceut Corp, Paramus, NJ 07652 USA

来源：

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY | 2000年 / 40卷

关键词：

serotonin; GPCR; adenylate cyclase; antisense; cognition;

D O I：

10.1146/annurev.pharmtox.40.1.319

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

5-ht(6) receptors are the latest serotonin receptors to be identified by molecular cloning. Their high affinity for a wide range of drugs used in psychiatry, coupled with their intriguing distribution in the brain, has stimulated significant interest. Antisense oligonucleotides, antipeptide antibodies, selective radioligands, knockout mice, and selective antagonists of the 5-ht(6) receptor have recently become available. Surprisingly, 5-ht(6) receptors appear to regulate cholinergic neurotransmission in the brain, rather than the expected interaction as modulators of dopaminergic transmission. This interaction predicts a possible role for 5-ht(6) receptor antagonists in the treatment of learning and memory disorders. Furthermore, polymorphisms in the sequence of the 5-ht(6) receptor gene may provide a genetic tool to further our understanding of the differential responses of patients to antipsychotic medications.

引用

收藏

页码：319 / 334

页数：16

相关论文

共 65 条

[1] Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence [J].

Arnt, J ;

Skarsfeldt, T .

NEUROPSYCHOPHARMACOLOGY, 1998, 18 (02) :63-101

[2] Stimulation of type 1 and type 8 Ca2+/calmodulin-sensitive adenylyl cyclases by the Gs-coupled 5-hydroxytryptamine subtype 5-HT7A receptor [J].

Baker, LP ;

Nielsen, MD ;

Impey, S ;

Metcalf, MA ;

Poser, SW ;

Chan, G ;

Obrietan, K ;

Hamblin, MW ;

Storm, DR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (28) :17469-17476

[3] Investigation of stretching behaviour induced by the selective 5-HT6 receptor antagonist, Ro 04-6790, in rats [J].

Bentley, JC ;

Bourson, A ;

Boess, FG ;

Fone, KCF ;

Marsden, CA ;

Petit, N ;

Sleight, AJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (07) :1537-1542

[4]

BENTLEY JC, 1997, J PSYCHOPHARMACOL, V11, P864

[5] CHARACTERIZATION OF AN ADENYLATE CYCLASE-LINKED SEROTONIN (5-HT1) RECEPTOR IN A NEURO-BLASTOMA X BRAIN EXPLANT HYBRID CELL-LINE (NCB-20) [J].

BERRYKRAVIS, E ;

DAWSON, G .

JOURNAL OF NEUROCHEMISTRY, 1983, 40 (04) :977-985

[6] Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand binding site of the 5-hydroxytryptamine(6) receptor [J].

Boess, FG ;

Monsma, FJ ;

Meyer, V ;

Zwingelstein, C ;

Sleight, AJ .

MOLECULAR PHARMACOLOGY, 1997, 52 (03) :515-523

[7]

Boess FG, 1998, J NEUROCHEM, V71, P2169

[8] Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells [J].

Boess, FG ;

Monsma, FJ ;

Carolo, C ;

Meyer, V ;

Rudler, A ;

Zwingelstein, C ;

Sleight, AJ .

NEUROPHARMACOLOGY, 1997, 36 (4-5) :713-720

[9] The 5-hydroxytryptamine, receptor-selective radioligand [3H]Ro 63-0563 labels 5-hydroxytryptamine receptor binding sites in rat and porcine striatum [J].

Boess, FG ;

Riemer, C ;

Bös, M ;

Bentley, J ;

Bourson, A ;

Sleight, AJ .

MOLECULAR PHARMACOLOGY, 1998, 54 (03) :577-583

[10] Residues in transmembrane regions III and VI contribute to the 5-ht6 receptor ligand binding site [J].

Boess, FG ;

Monsma, FJ ;

Bourson, A ;

Zwingelstein, C ;

Sleight, AJ .

ADVANCES IN SEROTONIN RECEPTOR RESEARCH: MOLECULAR BIOLOGY, SIGNAL TRANSDUCTION, AND THERAPEUTICS, 1998, 861 :242-243

← 1 2 3 4 5 6 7 →