Navigation Links
Led by advances in chemical synthesis, scientists find natural product shows pain-killing properties
Date:5/23/2011

JUPITER, FL, May 23, 2011 Scientists from the Florida campus of The Scripps Research Institute have for the first time accomplished a laboratory synthesis of a rare natural product isolated from the bark of a plant widely employed in traditional medicine. This advance may provide the scientific foundation to develop an effective alternative to commonly prescribed narcotic pain treatments.

The study, published May 23, 2011, in an advanced online edition of the journal Nature Chemistry, defines a chemical means to access meaningful quantities of the rare natural product conolidine. Based on data from mouse models, the study also suggests that synthetic conolidine is a potent analgesic as effective as morphine in alleviating inflammatory and acute pain, with few, if any, side effects.

In recent years, there has been significant interest in developing alternatives to opiate-based pain medications such as morphine. While widely prescribed for pain, morphine has a number of adverse side effects that range from the unpleasant to the lethal, including nausea, chronic constipation, addiction, and breathing depression.

The rare natural product central to the study is derived from the bark of a widely grown tropical flowering plant Tabernaemontana divaricata (also known as crepe jasmine). Long part of traditional medicine in China, Thailand, and India, extract from the leaves has been used as an anti-inflammatory applied to wounds, while the root has been chewed to fight the pain of toothache. Other parts of the plant have been used to treat skin diseases and cancer.

Conolidine belongs to a larger class of natural products, called C5-nor stemmadenines, members of which have been described as opioid analgesics, despite a substantial discrepancy between potent in vivo analgesic properties and low affinity to opiate receptors. Conolidine is an exceptionally rare member of this family for which no therapeutically relevant properties had ever been described. Despite the potential value of conolidine and related C5-nor stemmadenines as leads for therapeutics, efficient methods to prepare these molecules were lacking.

"This was a classic problem in chemical synthesis," said Glenn Micalizio, an associate professor in the Department of Chemistry, who initiated and directed the study, "which we were able to solve effectively and efficientlyan achievement that made subsequent assessment of the potential therapeutic properties of this rare natural product possible."

Micalizio and his colleagues began working on the synthesis of the molecule after they arrived at Scripps Florida in 2008.

Testing For Potency

Once the synthesis was complete, research shifted to pharmacology for evaluation. The pharmacological assessment, performed in the laboratory of Scripps Florida Associate Professor Laura Bohn, showed that the new synthetic compound has surprisingly potent analgesic properties.

"Her pharmacological studies confirmed that while it's not an opiate, it's nearly as potent as morphine," Micalizio said.

In various models of pain, the new synthetic compound performed spectacularly, suppressing acute pain and inflammatory-derived pain, two key measures of efficacy. Not only that, but the new compound passed easily through the blood-brain barrier, and was present in the brain and blood at relatively high concentrations up to four hours after injection.

Bohn herself was surprised by the compound's potency and by the fact it so readily enters the brain.

"While the pain-relieving properties are encouraging, we are still challenged with elucidating the mechanism of action," she said. "After pursuing more than 50 probable cellular targets, we are still left without a primary mechanism."

So far, the compound has shown remarkably few, if any, side effects, but that is something of a double-edged sword.

"The lack of side effects makes it a very good candidate for development," Bohn said. "On the other hand, if there were side effects, they might provide additional clues as to how the compound works at the molecular level."

That remains a mystery. While the synthetic compound might be as effective as morphine, it doesn't act at any of the receptors associated with opiates. In fact, it misses most of the major neurotransmitter receptors completely, suggesting it may be highly tuned towards relieving pain while not producing multiple side effects. While still in the early stages of development, further characterizations of conolidine may suggest further development as a human therapeutic for the treatment of pain.


'/>"/>

Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

Related medicine news :

1. Senate Committee Advances Disastrous Idaho Health Freedom Act
2. Neutrons poised to play big role in future scientific advances
3. SeqWright Advances Genomic Discovery With Isilon IQ
4. Greenway Medical Technologies Advances Patient-Provider Benefits
5. Fifty years of the light fantastic: Laser advances spark scientific progress
6. South Carolina Senate Banking & Insurance Committee Advances Medigap Bill to Full Senate by Overwhelming Vote
7. Leading Orthopaedic Surgeon and Regenerative Medical Authority Dr. Thomas A. Einhorn Advances Adult Stem Cell Therapy To Eliminate Hip Replacement Surgery
8. Advances in personalized medicine take center stage
9. Researchers make advances in understanding causes, treatments and outcomes of liver disease
10. Mayo Clinic researcher details next-era advances in use of scopes for cancer detection
11. Rochester advances understanding of deadly form of malaria
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2017)... ... April 28, 2017 , ... Ushio ... These lamps offer an instant energy-saving solution for F32T8 fluorescent lamps on most ... disconnect ballasts. These 50,000 hour rated lamps utilize the existing electronic ballast, saving ...
(Date:4/28/2017)... , ... April 28, 2017 , ... ... been previously exposed to more adverse experiences than children in the general population. ... such as abuse, neglect or other family challenges. While no fault of their ...
(Date:4/28/2017)... (PRWEB) , ... April 28, 2017 , ... ... or hERG liability could substantially improve drug safety and minimize the cost of ... for validating ion channel inhibition using cell lines and for cardiac toxicity using ...
(Date:4/28/2017)... ... ... Overseer at The House of Yahweh in Abilene, Texas, has published a new post that ... Yisrayl says with so many titles and names for the Creator, it’s hard for many ... Scripture, backed with a lot of research, the truth is undeniable. , “If you ...
(Date:4/28/2017)... ... ... Intellitec Solutions announced the publication of a case study ... solution that integrates to their PointClickCare EHR software package. With the guidance of ... now has the capability to achieve its goal for a comprehensive EHR solution, ...
Breaking Medicine News(10 mins):
(Date:4/20/2017)...  CVS Pharmacy, the retail division of CVS ... design to enhance the retail customer experience with ... and expanded beauty selections paired with informational signage ... offerings. Together with its innovative digital programs, these ... experience at CVS Pharmacy.  "Pharmacy ...
(Date:4/20/2017)... Research and Markets has announced the ... Application Analysis, Regional Outlook, Growth Trends, Key Players, Competitive Strategies ... ... was valued at US$ 7,167.6 Mn in 2015, and is ... a CAGR of 5.6% from 2016 to 2024. ...
(Date:4/20/2017)... 2017 Research and Markets has announced ... Services Market Analysis By Service (Manufacturing, Research), By Country, (Brazil, ... 2025" report to their offering. ... The Latin American pharmaceutical contract manufacturing services ... Low drug registration cost in Latin American countries ...
Breaking Medicine Technology: