Fentanyl analogues

Due to the success of fentanyl, Janssen and other pharmaceutical companies started to produce other legal fentanyl analogues with a wider range of potency and duration of action, including ... 

In 1979-1980, some illegal fentanyl analogues appeared that were being sold as substitutes for heroin on the street. Suddenly, a series of more than a dozen mysterious deaths occurred in southern California. Upon autopsy, the victims strongly looked as if they had overdosed on heroin however, no traces of heroin could be found in their bodies. Later, forensic chemists identified a fentanyl analogue (alpha-methyl-fentanyl) that was present in all of the victims. As it turns out, alpha-methyl-fentanyl was being sold on the streets under the name China White (Figure 7.2), because it resembled (and contained) pure synthetic heroin that was produced in Southeast Asia. 

Figure 7.2 China White powder, shown here, is a synthetic form of heroin that is very pure. China White that was tainted with illegal fentanyl analogues, which are hundreds of times more potent than heroin, caused numerous overdoses in heroin addicts in the late 1970s and early 1980s.

Users of fentanyl analogues report that these drugs produce a rapid rush or euphoria that is similar to that felt with heroin, followed by a sedated, dream-like state. As analgesics, they also produce a profound loss of pain sensation and have common unwanted side effects such as sleepiness and constipation. However, because they are so potent, fentanyl analogues can... 

The enhancement of potency due to the presence of an equatorial methyl group noted in the meperidine series also applies to fentanyl analogues. The ring nitrogen of the starting material (27-1) for this particular derivative is protected by a benzyl group since it will be replaced later by a somewhat more complex side chain. 

MeO-pyr-T, we are far away from any vocabulary of psychedelics. How is it different from, say, what one might expect from a Fentanyl analogue Here is a collection of trials that describe parenteral administration, and the quick development of an anesthesia. This compound may not be the new Fentanyl because of the nausea during what would be the recovery period. But what are the chances that, perhaps not with this compound, but with any of the obvious analogues that are screaming to be assayed, there just might be a useful clinical tool ... 

Essawi, M.Y.H. Fentanyl analogues with a modified propanamido group as potential affinity labels Synthesis and in vivo activity, Pharmazie 1999, 54, 307-308. 

Cocaine (Schedule I) Cocaine Base (Schedule I) Fentanyl (Schedule I) Fentanyl Analogue (Schedule I)... 

Sufentanil, a fentanyl analogue, is a highly lipid-soluble synthetic opioid with high affinity for OP3 (p) opioid receptors and a potency some 5-10 times that of fentanyl. It is a short-acting analgesic. 

A. Skulska, M. Kala, A. Parczewski, Fentanyl and its Analogues in Clinical and Forensic Toxicology, Przeglad Lekarski, 62, 2005. 

Figure 7.3 The chemical structure of fentanyl and its illegal analogues alpha-methyl-fentanyl and 3-methyl-fentanyl are shown here. Fentanyl was originally designed and marketed as an anesthetic, as it is 100 times stronger than morphine.

Tertiary arylacetamides appear to undergo hydrolysis to a very limited extent only. Hydrolysis of the synthetic opioid fentanyl (4.117) to despropa-noylfentanyl (4.118) was a very minor pathway in humans [76], No metabolites resulting from amide hydrolysis were detected for the fentanil analogues alfentanil (4.119) and sufentanil (4.120) [77], for which oxidative N-dealkylation was the main metabolic pathway. 

Most of the haemodynamic effects of opioids are related to decreased central sympathetic outflow, specific vagal effects or, in the case of morphine and pethidine, histamine release. Fentanyl and its analogues do not cause histamine release. All opioids, with the exception of pethidine, produce bradycardia by actions on the afferent fibres of the vagus and the nucleus tractus solitarius and nucleus commissuralis, which have very high densities of opioid receptors. Pethidine often produces tachycardia, possibly due to its structural similarity to atropine. In isolated heart or heart-muscle preparations, opioids produce a dose-related negative inotropic effect, but only at concentrations 100 to several thousand times those found clinically. 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

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