ANALGESIA Flower Power

RESEARCH HIGHLIGHTS

ANALGESIA Flower power

Opioids such as morphine pain. Many indole alkaloids have writhing response in a visceral pain are still considered to offer been isolated from this plant and model, and reduced nocifensive the most effective form implicated in analgesia, but this is the behaviours in a tonic and persistent of pain relief, despite first study to report the therapeutic pain model. having adverse effects effects of conolidine. Interestingly, conolidine showed such as addiction, Investigation of the biological no affinity for the μ-opioid receptor tolerance, depression properties of conolidine had not and it did not alter locomotor activity of breathing, been possible until now because of in an open field test, which suggests nausea and chronic its scarcity; it is isolated from the that conolidine does not increase constipation. stem bark of the shrub with a yield dopamine levels (a characteristic of Alternative, of just 0.00014%. However, despite all addictive substances). Although efficacious and safe its challenging structure, Micalizio conolidine’s mechanism of action analgesic agents are and colleagues have managed is unclear at present, these findings therefore still sought. to synthesise (±)-conolidine, suggest that it works through a Now, reporting in (+)-conolidine and (–)-conolidine different signalling pathway to Nature Chemistry, from the commercially available opioids and could therefore lack their Micalizio and colleagues pyridine in just nine steps with an unwanted side effects. The ability describe the synthesis of overall yield of 18%. to easily synthesize this compound conolidine, a non-opioid To investigate the potential in large quantities is greatly analgesic that might offer analgesic effects of synthetic advantageous for further testing in pain relief without having these conolidine in vivo, the authors neuropathic pain models and for adverse effects. injected 10–20 mg per kg developing a formulation that can Conolidine is a C5‑nor intraperitoneally into C57BL/6J be administered orally. stemmadenine that is found in the mice and examined their responses Monica Hoyos Flight bark of the tropical flowering shrub to various painful stimuli. Unlike Tabernaemontana divaricata, which opioids, conolidine did not promote ORIGINAL RESEARCH PAPER Tarselli, M. A. has been used for a long time in antinociception to acute thermal et al. Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain. Nature traditional Chinese, Ayurvedic and stimulation; however, like morphine Chem. 3, 449–453 (2011). Thai medicines to treat fever and and other analgesics, it prevented a