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Treating pain by blocking the 'chili-pepper receptor'

Date:
August 20, 2014
Source:
American Chemical Society
Summary:
Biting into a chili pepper causes a burning spiciness that is irresistible to some, but intolerable to others. Scientists exploring the chili pepper's effect are using their findings to develop a new drug candidate for many kinds of pain, which can be caused by inflammation or other problems. They have now reported their progress on the compound, which is being tested in clinical trials.

As anyone who has bitten into a chili pepper knows, its burning spiciness -- though irresistible to some -- is intolerable to others. Scientists exploring the chili pepper's effect are using their findings to develop a new drug candidate for many kinds of pain, which can be caused by inflammation or other problems. They reported their progress on the compound, which is being tested in clinical trials, in ACS' Journal of Medicinal Chemistry.

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Laykea Tafesse and colleagues explain that decades ago, scientists had pegged a compound called capsaicin as the active ingredient in chili peppers that causes fiery pain. In the 1990s, researchers were able to sequence the genetic sequence for the protein "receptor" that capsaicin attaches to in the body. The receptor is a protein on cells that acts as a gate, allowing only certain substances into a cell.

The advance launched a hunt for compounds that can block this gate, cut off the pain signal and potentially treat pain that current drugs are no match for. Some of the molecules resulting from this search have been tested in people but cause unwanted side effects, or they wouldn't work well as oral medication. Tafesse's team wanted to explore variations on this theme to find a better drug candidate.

They produced more than two dozen similar compounds, each with its own unique molecular tweak. They tested them in the lab and in animals for the traits they were looking for, such as potency, safety, the ability to dissolve in water and whether they can be taken orally. One prospect showed the most promise, and it has advanced into clinical trials.


Story Source:

The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length.


Journal Reference:

  1. Laykea Tafesse, Toshiyuki Kanemasa, Noriyuki Kurose, Jianming Yu, Toshiyuki Asaki, Gang Wu, Yuka Iwamoto, Yoshitaka Yamaguchi, Chiyou Ni, John Engel, Naoki Tsuno, Aniket Patel, Xiaoming Zhou, Takuya Shintani, Kevin Brown, Tsuyoshi Hasegawa, Manjunath Shet, Yasuyoshi Iso, Akira Kato, Donald J. Kyle. Structure–Activity Relationship Studies and Discovery of a Potent Transient Receptor Potential Vanilloid (TRPV1) Antagonist 4-[3-Chloro-5-[(1S)-1,2-dihydroxyethyl]-2-pyridyl]-N-[5-(trifluoromethyl)-2-pyridyl]-3,6-dihydro-2H-pyridine-1-carboxamide (V. Journal of Medicinal Chemistry, 2014; 57 (15): 6781 DOI: 10.1021/jm500818a

Cite This Page:

American Chemical Society. "Treating pain by blocking the 'chili-pepper receptor'." ScienceDaily. ScienceDaily, 20 August 2014. <www.sciencedaily.com/releases/2014/08/140820110544.htm>.
American Chemical Society. (2014, August 20). Treating pain by blocking the 'chili-pepper receptor'. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2014/08/140820110544.htm
American Chemical Society. "Treating pain by blocking the 'chili-pepper receptor'." ScienceDaily. www.sciencedaily.com/releases/2014/08/140820110544.htm (accessed October 24, 2014).

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