Monthly Archives: August 2014

Treating pain by blocking the ‘chili-pepper receptor’


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 reported their progress on the compound, which is being tested in clinical trials, in ACS’ Journal of Medicinal Chemistry.

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.

Study: 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 (V116517) as a Clinical Candidate for Pain Management, 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, and Donald J. Kyle, J. Med. Chem., DOI: 10.1021/jm500818a, published 24 July 2014.





DEA Rules Tramadol a Schedule IV Drug



The Drug Enforcement Administration (DEA) has officially changed tramadol from a non-classified drug to a Schedule IV substance under the Controlled Substances Act, effective Aug. 18, 2014. This change was published in the Federal Register (2014;79:37624).

Ever since the FDA approved tramadol for the management of chronic pain in 1995, there has been an ongoing debate over its safety, potential for abuse and regulation.

In 2010, the assistant secretary of the Department of Health and Human Services (HHS) provided the DEA with evidence in favor of a scheduling change. After a review of the available data and the recommendation from HHS, the DEA published a notice of proposed rulemaking to classify tramadol as a Schedule IV controlled substance in November 2013.

The notice allowed anyone interested to submit written comments on the proposal: 16 supported the change, nine opposed it and two did not take a position. The opponents argued that controlling tramadol would limit its access to elderly patients and called for a solution to ensure timely access for patients in long-term care facilities.

The DEA maintained, however, that the change should not hinder valid access to the drug for those with an appropriate medical condition and legal prescription in any setting.


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