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Morphine-Like Synthetic Pain Killer Lacks Side Effects

By LabMedica International staff writers
Posted on 06 Jun 2011
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A team of pharmaceutical chemists has successfully synthesized conolidine, a rare natural product that is a potent analgesic as effective as morphine in alleviating inflammatory and acute pain, with few, if any, side effects.

Management of chronic pain is usually based on opioid analgesics despite the fact that they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea, and chronic constipation.

In the current study investigators at the Scripps Research Institute (Jupiter, FL, USA) sought to develop a method for the synthesis of conolidine, a rare C5-nor stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic, and Thai medicine). Details of their research were published in the May 23, 2011, online edition of the journal Nature Chemistry.

"This was a classic problem in chemical synthesis," said Dr. Glenn Micalizio, associate professor in of chemistry at the Scripps Research Institute, "which we were able to solve effectively and efficiently--an achievement that made subsequent assessment of the potential therapeutic properties of this rare natural product possible."

The synthetic conolidine was tested in a mouse model of tonic and persistent pain. Results showed that the new synthetic compound suppressed acute pain and inflammatory-derived pain, two key measures of efficacy. 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.

"Pharmacological studies confirmed that while it is not an opiate, it is nearly as potent as morphine," said Dr. Micalizio.

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