The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept

被引：700

作者：

Szallasi A. ^{[1
,5
]}

Cortright D.N. ^{[2
]}

Blum C.A. ^{[3
]}

Eid S.R. ^{[4
]}

机构：

[1] Department of Pathology, Monmouth Medical Center, Long Branch

[2] Department of Biochemistry and Molecular Biology, Neurogen Corporation, Branford

[3] Department of Chemistry, Neurogen Corporation, Branford, MA

[4] Department of Pain Research, Merk Research Laboratories, West Point Philadelphia, PA

[5] Drexel University College of Medicine, Philadelphia, PA

来源：

Nature Reviews Drug Discovery | 2007年 / 6卷 / 5期

关键词：

D O I：

10.1038/nrd2280

中图分类号：

学科分类号：

摘要：

The clinical use of TRPV1 (transient receptor potential vanilloid subfamily, member 1; also known as VR1) antagonists is based on the concept that endogenous agonists acting on TRPV1 might provide a major contribution to certain pain conditions. Indeed, a number of small-molecule TRPV1 antagonists are already undergoing Phase I/II clinical trials for the indications of chronic inflammatory pain and migraine. Moreover, animal models suggest a therapeutic value for TRPV1 antagonists in the treatment of other types of pain, including pain from cancer. We argue that TRPV1 antagonists alone or in conjunction with other analgesics will improve the quality of life of people with migraine, chronic intractable pain secondary to cancer, AIDS or diabetes. Moreover, emerging data indicate that TRPV1 antagonists could also be useful in treating disorders other than pain, such as urinary urge incontinence, chronic cough and irritable bowel syndrome. The lack of effective drugs for treating many of these conditions highlights the need for further investigation into the therapeutic potential of TRPV1 antagonists.

引用

页码：357 / 372

页数：15

共 179 条

[21]

Huang S.M., Et al., An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors, Proc. Natl Acad. Sci. USA, 99, pp. 8400-8405, (2002)

[22]

Hwang S.W., Et al., Direct activation of capsaicin receptors by products of lipoxygenases: Endogenous capsaicin-like substances, Proc. Natl Acad. Sci. USA, 97, pp. 6155-6160, (2000)

[23]

Shin J., Et al., Bradykinin-12-lipoxygenase-VR1 signalling pathway for inflammatory hyperalgesia, Proc. Natl Acad. Sci. USA, 99, pp. 10150-10155, (2002)

[24]

Moriyama T., Et al., Sensitization ofTRPV1 by EP1 and IP reveals peripheral nociceptive mechanisms of prostaglandins, Mol. Poin, 1, pp. 3-9, (2005)

[25]

Tominaga M., Wada M., Masu M., Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia, Proc. Natl Acad. Sci. USA, 98, pp. 6951-6956, (2001)

[26]

Negri L., Et al., Impaired nociception and inflammatory pain sensation in mice lacking the prokineticin receptor PKR1: Focus on interaction between PKR1 and the capsaicin receptor TRPV1 in pain behavior, J. Neurosci, 26, pp. 6716-6127, (2006)

[27]

Ahern G.P., Wang X., Miyares R.L., Polyamines are potent ligands for the capsaicin receptor TRPV1, J. Biol. Chem, 281, pp. 8991-8995, (2006)

[28]

Cuypers E., Yanagihara A., Karlsson E., Tytgat J., Jellyfish and other cnidarian envenomations cause pain by affecting TRPV1 channels, FEBS Lett, 580, pp. 5728-5732, (2006)

[29]

Siemens J., Et al., Spider toxins activate the capsaicin receptor to produce inflammatory pain, Nature, 444, pp. 208-212, (2006)

[30]

Bhave G., Et al., cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation, Neuron, 35, pp. 721-731, (2002)

← 1 2 3 4 5 6 7 8 9 10 →