Haloperidol Narcotics

An important step for the treatment of severe pain was made in the early 1960s Paul Janssen s exploitation of 4-piperidone chemistry proved remarkably successful in that it led to the clinical use of both a major tranquilizer (haloperidol) and a potent narcotic analgesic, fentanyl. Fentanyl is related to pethidine and also to basic anilides with analgesic properties and is characterized by high potency and short duration of action. Again, a series of derivatives was synthesized over the following decades which led to several products for clinical use, however fentanyl is still very important for the treatment of severe pain. 

Figure 2.3 Dextromethorphan 6, the unnatural enantiomer of a narcotic morphine analog, is an antitussive drug. The antidiarrhea drug loperamide 7 and the neuroleptic drug haloperidol 8 also resulted from structural modification of morphine. The morphine antagonist nalorphine 9 differs from the opioid agonist morphine 3 (Figure 2.2) only by having an N-allyl group instead of the N-methyl group.

Haloperidol was introduced for the treatment of psychoses in Europe in 1958 and in the United States in 1967 (Fig. 22.7). it is an effective aiternative to more famiiiar antipsychotic phenothiazine drugs and also is used for the manic phase of bipolar (manic-depressive) disorder. Haloperidol decanoate has been introduced as depot maintenance therapy. When injected every 4 to 6 weeks, the drug appears to be as effective as daily orally administered haloperidol. Other currently available (mostly in Europe) butyrophenones include the very potent spiperone (spiroperidol) as well as trifluperidol and droperidol. Droperidol, a short-acting, sedating butyrophenone, is used in anesthesia for its sedating and antiemetic effects and, sometimes, in psychiatric emergencies as a sedative-neuroleptic. Droperidol often is administered in combination with the potent narcotic analgesic fentanyl for preanesthetic sedation and anesthesia. 

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