Fentanyl structures

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.

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. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Figure 15.5. Structures of some "designer drugs" of abuse. Compare the structure of alpha-methyl fentanyl with that of fentanyl, MMP+ with that of pethidine, and ecstasy with that of methamphetamine.

The gold standard of opiate pain relievers is morphine. It was one of the first compounds extracted, isolated, and purified from the opium poppy, and it continues to be one of the most widely used pain relievers today. Morphine and other opiate drugs such as heroin, codeine, oxycodone, and hydrocodone have very similar chemical structures (Figure 3.2). However, other opiates such as fentanyl and meperidine (Demerol) have a slightly different structure (Figure 3.3). 

Fig. 3.1 Morphine 1 has been the lead structure for the development of the major analgesic fentanyl 2, the antitussive drug dextromethorphan 3, the constipating drug loperamide 4, and the neuroleptic drug haloperidol 5.

Modification of the chemical structure of natural substances has frequently led to pharmaceuticals with enhanced potency. An illustrative example is fentanyl, which acts like morphine but requires a dose only 0.1-0.05 times that of the parent substance. Derivatives of fentanyl such as carfentanyl (employed in veterinary anesthesia of large animals) are actually 5000 times more potent than morphine. 

Figure 2.2 Morphine 3 was the lead structure for many structurally much simpler strong analgesics, e.g., pethidine 4 and fentanyl 5.

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