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:6/25/2016)... ... 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned ... the David Geffen School of Medicine at UCLA. He trained in Internal Medicine at ... fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity ...
(Date:6/25/2016)... , ... June 25, 2016 , ... On Friday, June ... a Bronze Wellness at Work award to iHire in recognition of their exemplary accomplishments ... of the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott ...
(Date:6/24/2016)... Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... surgery procedures that most people are unfamiliar with. The article goes on to state ... procedures, but also many of these less common operations such as calf and cheek ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary ... Dallas that it will receive two significant new grants to support its work ... marked its 25th anniversary by recognizing patients, medical professionals and scientists for their ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... ANGELES , June 23, 2016 ... CAPR ), a biotechnology company focused ... therapeutics, today announced that patient enrollment in its ... in Duchenne) has exceeded 50% of its 24-patient ... enrollment in the third quarter of 2016, and ...
(Date:6/23/2016)... -- , , , WHEN: , ... , , , LOCATION: , , , Online, with free ... EXPERT PANELISTS:  , , , Frost & Sullivan,s Global Vice President ... Industry Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... is witnessing an exceptional era. Several new demand spaces, such as ...
(Date:6/23/2016)... 23, 2016 Revolutionary technology includes ... Oticon , industry leaders in advanced audiology and hearing ... Oticon Opn ™, the world,s first internet connected hearing ... IoT devices.      (Photo: http://photos.prnewswire.com/prnh/20160622/382240 ... number of ,world firsts,: , TwinLink™ - ...
Breaking Medicine Technology: