A µ-opioid receptor superagonist analgesic with minimal adverse effects - PubMed
3 hours ago
- #adverse effects
- #analgesic
- #μ-opioid receptor
- A novel MOR agonist named N-desethyl-fluornitrazene (DFNZ) is identified as a superagonist with supramaximal intrinsic efficacy, derived from synthetic benzimidazole opioids called nitazenes.
- DFNZ produces effective analgesia in rodents while showing minimal adverse effects such as no respiratory depression, tolerance, MOR downregulation after repeated exposure, and limited effects on dopamine neurotransmission and reinforcing behavior.
- The compound has impaired brain penetrance, a unique spatiotemporal MOR cellular signaling profile, and diminished efficacy at the MOR-GAL1 heteromer, challenging the idea that high-efficacy MOR agonists cannot be safe therapeutic agents.