Alfentanil is an opioid analgesic with a rapid onset of action. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. Alfentanil, marketed under the trade name Alfenta, Rapifen in Australia is indicated for the management of postoperative pain and the maintenance of general anesthesia.

Brifentanii, a potent narcotic analgesic structurally similar to alfentanil, that was studied in clinical trials in the early 1990s. The effects of brifentanil are very similar to those of alfentanil, with strong but short lasting analgesia and sedation, and particularly notable itching and respiratory depression. Side effects of Brifentanii are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Trefentanil is a short-acting synthetic opioid of the piperidine class. The drug caused potent analgesia with the peak effect occurring 3 min after injection. There was no significant difference in analgesic potency of trefentanil and alfentanil as measured by tolerance to tibial pressure at 3 min. Trefentanil had a pharmacokinetic and pharmacodynamic profile similar to alfentanil, with a small extent of tissue distribution and a rapid blood/brain equilibration. Trefentanil caused significant respiratory depression at doses of 32 ug/kg and 64 ug/kg. It is a mu-opioid receptor agonist. Trefentanil produced naloxone reversible anti-nociception equi-efficacious to that of fentanyl.