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TrefentanilTrefentanil, also known by the name A-3665, is a powerful and short acting opioid analgesic and anaesthetic drug. It is an analogue of fentanyl that was first developed in 1992. It belongs to the piperidine class of fentanyl analogues.

Trefentanil is most similar to the fentanyl analogue alfentanil. In one study it was shown to cause potent analgesia in comparison to placebo. The peak effect of the drug occurred 3 minutes after injection. Researchers found no difference in the pain relief when alfentanil was compared to trefentanil in a tibia pressure test.

Trefentanil continued to produce significant pain relieving effects up to 15 minutes after injection at a dose of 16 μg/ Kg which would be a total dose of 1.33 mg for an average male weighing 83 Kg.

Crucially, Trefentanil was shown to cause significant respiratory depression at doses of 32 μg/ Kg and 64 μg/ Kg, whereas alfentanil did not produce respiratory depression at these doses.

Over the dosage range examined in this study, Trefentanil showed an equal potency to Alfentanil. However it showed a shorter duration of action and caused more respiratory depression.

Alfentanil already has a heavy suppressing effect on breathing. Therefore Trefentanil was never pursued as a medical drug as it would be more likely to cause respiratory arrest in patients.

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Other side effects of Trefentanil include nausea and itching. Fentanyl analogues like Trefentanil also tend to be more heavily sedating than other opioids.

Fentanyl analogues have a high affinity for the μ opioid receptor. This is one of the targets of drugs like heroin, morphine and oxycodon. For this reason fentanyl and its analogues may be abused by heroin and opiate addicts.

The first documented large scale outbreak of fentanyl analogue abuse centred on California in the United States between 1979 and 1988. At this time 112 deaths were attributed to the use of  alpha-methylfentanyl.

At the turn of the 21st Century fentanyl analogues were responsible for hundreds of deaths in the former Soviet republics in Eastern Europe and especially Estonia.

Fentanyl analogues like Trefentanil make particularly dangerous recreational drug compounds for a number of reasons.

First when compared to morphine or heroin, fentanyl analogues cause a greater respiratory depression relative to the euphoria or “high”.  Death by respiratory arrest is the most common form of death with these compounds.

Secondly, they are extremely potent. They are many hundreds of times more potent than heroin and morphine. An amount that looks like a few grains of salt might be enough to kill. Thus it is easy to see how a small miscalculation or error in preparation could lead to a massive overdose. In fact, the drugs are that powerful that it is possible to overdose from splashing a solution of the drug on the skin.

The high produced by fentanyl and its analogues is generally considered to be less intense than that produced by heroin, oxycodon and morphine. In fact fentanyl analogues only tend to surface when there is a scarcity of heroin in the black market. In general addicts tend to prefer the more traditional opiates like oxycodon and heroin.