Haloperidol Essay

Discovery, structure, class and associated physiochemical properties

Haloperidol is an antipsychotic drug used in the treatment of schizophrenia. It was discovered by Bert Hermans in 1958 at Janssen Laboratories in Belgium. Haloperidol is placed in the class of butyrophenones. The chemical formula for haloperidol is C21H23ClFNO2. The IUPAC nomenclature for haloperidol is 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one.

Figure 1: 2-D structure of haloperidol (taken from https://pubchem.ncbi.nlm.nih.gov/compound/3559)

Tacke et al (2008) analysed haloperidol in order to determine the physicochemical properties of the drug. At a pH of 7.4, it was discovered that haloperidol has a distribution coefficient (Log D) of

The drug is widely distributed around the body, with more than 90% binding to plasma proteins. Most of the drug is found in the liver, however, haloperidol is also found in other organs (e.g. brain, heart and lungs), hair, saliva and breast milk.

Metabolism of haloperidol takes place in the liver. The piperidine nitrogen in haloperidol is oxidised, by oxidative dealkylation, to piperidine metabolites and fluorophenylcarbonic acids. The butyrophenones carbonyl in haloperidol is reduced to carbinol which then forms hydroxyhaloperidol, a metabolite of haloperidol with reduced activity. Intrinsic clearance of haloperidol is due to glucoronidation by uridine diphosphoglucose glucuronosyltransferase, oxidation by cytochrome P450 and reduction by carbonyl reductase.

The elimination half-life for haloperidol is 12-38 hours. Complete elimination of an oral dose of haloperidol takes 4 weeks. Five days after the administration of haloperidol, approximately 40% of the dose of haloperidol will be excreted in urine and 15% will be excreted in the faeces. Approximately 1% of the haloperidol administered will be excreted, in urine, in its original

Kane et al (2002) carried out a study on the safety and efficacy of antipsychotics. They found that out of 103 individuals, receiving haloperidol, 25% suffered from headaches, 19% had anxiety, 8% had blurred vision,13% felt drowsy, 6% had nausea, 10% were vomiting and 36% of patients taking haloperidol had extrapyramidal symptoms. Of the 103 patients being treated with haloperidol, the mean increase in prolactin levels was 22.5ng/mL. Increased prolactin (hyperprolactinaemia) can cause symptoms including increased milk production (galactorrhoea), gynaecomastia, amenorrhoea and lack of sexual