Morphine analogue fentanyl

One important analogue of morphine is fentanyl, a clinically used narcotic that is about 100 times more potent than morphine. Several analogues have been synthesised such as sufentanil, alfentanil, lofentanil and, even more interestingly, structurally related compounds with different activities such as astemizole (antihistaminic), droperidol (tranquillizing), loperamide (antidiarrheal) and lorcainide (antiarrhythmic) [50]. 

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. 

Diampromidc (III) and its related anilides have potencies that are comparable with those of morphine " they have shown addiction liability, however, and have not appeared on the market. The closely related cyclic derivative fentanyl (Table 22-3. A-17) is used in surgery. The benzimidazoles, such as elonitazcnc (IV). arc very potent analgesics hut. show the highe.st addiction liabilities yet encountered. -" Po.ssibly an exception to feature 3. and the only one that has been encountered, may be the cyclohcxyl analogue of A-6 (Table 22-3). which has significant activity. Eddy mentions two passible exceptions to feature 4 in addition to fentanyl. 

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