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Clinical data
CAS Number
PubChem CID
E number{{#property:P628}}
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Chemical and physical data
Molar mass466.551 g/mol

Trefentanil (A-3665) is an opioid analgesic that is an analogue of fentanyl and was developed in the early 1990s.

Trefentanil is most similar to short-acting fentanyl analogues such as alfentanil. In comparative studies, trefentanil was slightly more potent and shorter acting than alfentanil as an analgesic,[1] but induced significantly more severe respiratory depression.[2] For this reason trefentanil has not been adopted for clinical use, although it is still used in research.

Trefentanil has very similar effects to alfentanil, much like those of fentanyl itself but more potent and shorter lasting. Side effects of fentanyl analogues are similar to those of fentanyl, and include itching, nausea and potentially serious respiratory depression which can be life-threatening. The risk of respiratory depression is especially high with potent fentanyl analogues such as alfentanil and trefentanil, and these drugs pose a significant risk of death if used outside of a hospital setting with appropriate artificial breathing apparatus available.


  1. Lemmens HJ, Dyck JB, Shafer SL, Stanski DR. Pharmacokinetic-pharmacodynamic modeling in drug development: application to the investigational opioid trefentanil. Clinical Pharmacology and Therapeutics. 1994 Sep;56(3):261-71.
  2. Cambareri JJ, Afifi MS, Glass PS, Esposito BF, Camporesi EM. A-3665, a new short-acting opioid: a comparison with alfentanil. Anesthesia and Analgesia. 1993 Apr;76(4):812-6.