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Non-fentanyl derived novel synthetic opioids (NSOs) have initially emerged worldwide as non-illegal drugs diffused to replace heroin and thus circumvent prohibition laws, resulting in numerous abuse reports and overdose cases, especially across United States and Europe (Carroll et al., 2012; Armenian et al., 2017b; Baumann et al., 2017; Fabregat-Safont et al., 2017).

These NSOs are a broad family of analgesics and anesthetics, mainly synthesized in the 1970s, acting at the mu (μ) opioid receptor, but also at the delta (δ) and kappa (κ) ones. Shop1 The power of physiological and psychological effects is different according to the specific synthetic opioid being used and the type of receptor that is activated or inhibited (Baumann et al., 2017; European Monitoring Centre for Drugs, and Drug Addiction [EMCDDA], 2017).

To precisely define this particular class of NSOs, it is worth mentioning that the alkaloid compounds naturally found in the opium poppy plant are defined opiates and include, among others, morphine, codeine, and thebaine as principal alkaloids.

Instead, substances such as hydromorphone, oxymorphone, and heroin are semisynthetic opioids made from morphine with pharmacological properties similar to those of opiates and affinity for one of the 7-transmembrane G protein-coupled opioid receptors (Raffa et al., 2018).

Shop1 All the above reported opioids belong to the phenanthrene family, while the family of benzomorphans include, e.g., pentazocine phenazocine, dezocine, and eptazocine, developed through the modification of the basic phenanthrene structure of morphine (Cittern et al., 1986). Conversely, methadone is a phenylheptylamine agent whereas meperidine is a phenylpiperidine derivative (Knapp, 2002; Raffa et al., 2018).