Fentanyl and the 4-Anilinopiperidine Group of Analgesics

Abstract

Paul Janssen’s exploitation of 4-piperidone chemistry during the early 1960s proved remarkably successful in that it led to the clinical use of both a major tranquillizer (haloperidol)⁽¹⁾ and a potent narcotic analgesic, fentanyl.⁽²⁾ Fentanyl (1, Sublimaze, Leptanol) is related to pethidine and also to basic anilides with analgesic properties such as diampromide 2 (p. 311) and is characterized by high potency and short duration of action. Thus, in mice (tail-clip method) fentanyl is almost 200 times as active as morphine by the sc route and has a faster onset and shorter duration of action than the standard

drug. It shows the usual morphinelike effects, namely, Straub tails, mydriasis, and constipation in mice; in dogs and cats it causes respiratory depression but is devoid of emetic action.⁽³⁾ A clinical study in postsurgical patients and healthy volunteers showed 0.2 mg fentanyl to be equianalgesic with 10 mg morphine (im route) and the two drugs had similar side effects.⁽⁴⁾ The respiratory action of fentanyl in healthy males was judged to be somewhat greater than that of pethidine at equianalgesic dose levels.⁽⁵⁾ The rapid onset and short duration of action of fentanyl make it particularly well suited for use in neuroleptanalgesia and it has now achieved widespread use in surgical analgesia,⁽⁶⁾ especially when given in combination with a major tranquilizer such as droperidol (3) (Thalamontal contains fentanyl, 50 μg, and droperidol, 2.5 mg/ml).⁽⁷⁾