Atoxifent

Atoxifent
Clinical data
Drug class	painkiller; opioid
Identifiers
	IUPAC name 3-[(1S,5R)-3-(3-phenylpropyl)-3,8-diazabicyclo[3.2.1]octan-8-yl]phenol;
CAS Number	3047944-50-0;
PubChem CID	171663348;
ChEMBL	ChEMBL5523416;
Chemical and physical data
Formula	C21H26N2O
Molar mass	322.452 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1C[C@H]2CN(C[C@@H]1N2C3=CC(=CC=C3)O)CCCC4=CC=CC=C4;
	InChI InChI=InChI=1S/C21H26N2O/c24-21-10-4-9-18(14-21)23-19-11-12-20(23)16-22(15-19)13-5-8-17-6-2-1-3-7-17/h1-4,6-7,9-10,14,19-20,24H,5,8,11-13,15-16H2/t19-,20+; Key:PEXKBSSCTUNEBX-BGYRXZFFSA-N;

Atoxifent It is an extremely potent opioid; its pain-relieving effect is comparable to that of fentanyl, and atoxifent, even at doses that induce complete analgesia, does not cause severe respiratory depression.^[1]^[2]

Pharmacology

Pharmacodynamics

Atoxifent is an agonist of the μ-opioid and δ-opioid receptors. its EC₅₀ value for MOR is 0.39 ± 0.03 nM, with an efficacy (E_max) of 98.9 ± 0.6 per cent. Atoxifent is a partial agonist of δ-opioid receptors with an EC₅₀ value of 2.18 ± 0.50 nM and an E_max of 56.8 ± 11.0% it is a full κ-opioid receptor antagonist with an EC₅₀ value of 356.50 ± 106.49 nM and an E_max of 93.0 ± 2.0 per cent. It showed no affinity for nociceptin receptors.^[1]^[2]

References

1 2 Vu LY, Luo D, Johnson K, Denehy ED, Songrady JC, Martin J, et al. (June 2024). "Searching for Synthetic Opioid Rescue Agents: Identification of a Potent Opioid Agonist with Reduced Respiratory Depression". Journal of Medicinal Chemistry. 67 (11): 9173–9193. doi:10.1021/acs.jmedchem.4c00333. PMC 12054644. PMID 38810170.
1 2 Trivedi RR, Luo D, Hessing MC, Prantzalos E, Alilain WJ, Turner JR, et al. (November 2025). "N-(3-Hydroxyphenyl)-3,8-diazabicyclooctanes as opioid receptors probes. 1. Investigation of the phenolic hydroxyl group". European Journal of Medicinal Chemistry. 298 117991. doi:10.1016/j.ejmech.2025.117991. PMC 12374581. PMID 40730064.

[Vu_2024-1] 1 2 Vu LY, Luo D, Johnson K, Denehy ED, Songrady JC, Martin J, et al. (June 2024). "Searching for Synthetic Opioid Rescue Agents: Identification of a Potent Opioid Agonist with Reduced Respiratory Depression". Journal of Medicinal Chemistry. 67 (11): 9173–9193. doi:10.1021/acs.jmedchem.4c00333. PMC 12054644. PMID 38810170.

[Trivedi_2025-2] 1 2 Trivedi RR, Luo D, Hessing MC, Prantzalos E, Alilain WJ, Turner JR, et al. (November 2025). "N-(3-Hydroxyphenyl)-3,8-diazabicyclooctanes as opioid receptors probes. 1. Investigation of the phenolic hydroxyl group". European Journal of Medicinal Chemistry. 298 117991. doi:10.1016/j.ejmech.2025.117991. PMC 12374581. PMID 40730064.

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