Szpakowska, M., Decker, A.M., Meyrath, M. et al. The natural analgesic conolidine targets the newly identified opioid scavenger ACKR3/CXCR7. Sig Transduct Target Ther 6, 209 (2021). doi: 10.1038/s41392-021-00548-w
Authors: Martyna Szpakowska, Ann M. Decker, Max Meyrath, Christie B. Palmer, Bruce E. Blough, Ojas A. Namjoshi & Andy Chevigné
Authors: Martyna Szpakowska, Ann M. Decker, Max Meyrath, Christie B. Palmer, Bruce E. Blough, Ojas A. Namjoshi & Andy Chevigné
The atypical chemokine receptor ACKR3 has recently been reported to act as an opioid scavenger with unique negative regulatory properties towards different families of opioid peptides. Here, we show that conolidine, a natural analgesic alkaloid used in traditional Chinese medicine, targets ACKR3, thereby providing additional proof of a correlation between ACKR3 and pain modulation and opening alternative therapeutic avenues for the treatment of chronic pain.
While conolidine was shown to bind to serotonin-3 ion channel, the norepinephrine transporter, N-type Cav2.2 calcium channels, as well as several GPCRs including the α2B adrenergic (ADRA2B), α2C adrenergic (ADRA2C), and histamine-2 (HRH2) receptors,5 the low affinity of these interactions suggests that they do not mediate the primary mechanism of action of conolidine.