Haloperidol chlorpromazine

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

Antipsychotics Reduce hallucinations and delusions Chlorpromazine, haloperidol, clozapine... 

Drugs that are successful in treating the disease act as dopamine receptor blockers and are known as antipsychot-ics or neuroleptics (e.g. chlorpromazine, haloperidol). Antipsychotic drags reduce some of the symptoms, especially the delusions and hallucinations. A side-effect of the drugs is that they can result in symptoms similar to those seen in patients with Parkinson s disease. This is not surprising, since the hypothesis to explain Parkinson s disease is too low a concentration of dopamine in a specific area of the brain (see below). 

The work that has been done with chlorpromazine, haloperidol, and pimozide suggests that these drugs are metabolized more rapidly in children than in adults (Morselli et ah, 1982 Sallee et ah, 1987 Furlanut et ah, 1990). In addition, it appears that larger doses of chlorpromazine and haloperidol per body weight are needed in young people to achieve the same plasma concentrations as those in adults (Morselli et ah, 1979 Rivera-Calimlim et ah, 1979). 

There are several antipsychotics that are substrates to CYP2D6 (von Bahr et ah, 1991 Jerling et ah, 1996 Ring et ah, 1996 (Fang and Gorrod, 1999 Flockhart and Oesterheld, 2000) (Table 26.3). Moreover, several antipsychotics may act as inhibitors of CYP2D6-mediated biotransformation. These include thioridazine, chlorpromazine, haloperidol, fluphenazine, and pimozide (Desta et ah, 1998 Shin et ah, 1999). Of particular salience is the fact that the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and paroxetine are metabolized to a significant extent by this isoenzyme. 

D2 receptor, albeit with different specificity. Older examples of dopamine antagonists are chlorpromazine, haloperidol and many derivatives of these prototype compounds. Newer antipsychotic drugs such as risperidone, olanzapine and quetiapine have retained this mechanism of action, although no longer exclusively. 

After dopamine was identified as a neurotransmitter in 1959, it was shown that its effects on electrical activity in central synapses and on production of the second messenger cAMP by adenylyl cyclase could be blocked by antipsychotic drugs such as chlorpromazine, haloperidol, and thiothixene. This evidence led to the conclusion in the early 1960s that these drugs should be considered dopamine-receptor antagonists and was responsible for the dopamine hypothesis of schizophrenia described earlier in this chapter. The antipsychotic action is now thought to be produced (at least in part) by their ability to block dopamine in the mesolimbic and mesocortical systems. 

In either the presence or absence of GTP, half-maximal stimulation of enzyme activity is achieved with 3 uM dopamine. Both 6,7-ADTM and epinine (K-methyl dopamine) stimulate adenylate cyclase activity to the same degree as does dopamine (Figure 8). In contrast, apomorphine is a partial agonist eliciting only 30 of the maximal effect of dopamine. The dopamine-stimulated adenylate cyclase activity is selectively blocked by cis-flupenthixol rather than the trans-isomer of this antagonist (JJL). Among the antagonists tested, the order of potency is cis-flupenthixol = fluphenazine > chlorpromazine > haloperidol > trans-flupenthixol (Table I). 

Fig. 13.1 Chemical structure of clozapine, some of its structural analogues, typical (chlorpromazine, haloperidol) and atypical antipsychotics (risperidone, ziprasidone, sertindole and amisulpride) unrelated to clozapine.

Identical twin brothers, aged 37 years, had both suffered from bipolar disorder since their early twenties and had been treated with chlorpromazine, haloperidol, lithium, and carbamazepine before developing priapism. One of them developed priapism after taking trazodone 400 mg/day, and in the 2 years after the initial episode he suffered recurrent painless erections. Initially they occurred daily and lasted 4-5 hours. During a relapse of mania at age 37, he was given oral zuclopenthixol 40 mg/day. On the tenth day he presented with priapism of 4 days duration, which persisted despite zuclopenthixol withdrawal, needle aspiration, and phenylephrine instillation, but subsided 2 weeks later with conservative management. The... 

Giannini AJ, Nageotte C, Loiselle RH, Malone DA, Price WA. Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis DA-2 receptor specificity. J Toxicol Clin Toxicol 1984-1985 22(6) 573-9. 

A 37-year-old man who had abused metamfetamine, paint thinner, psychotomimetic drugs, and alcohol for 20 years was given chlorpromazine, haloperidol, and fluni-trazepam just before surgery. After spinal anesthesia he was given propofol 5 mg/kg/hour intravenously. However, euphoria and excitement occurred 10 minutes after the start of the infusion and he had excitement, hallucinations, and delirium. His symptoms were suppressed by intravenous haloperidol 5 mg. 

PROPANOLOL, TIMOLOL CHLORPROMAZINE, HALOPERIDOL t plasma concentrations and efficacy of both chlorpromazine and propranolol during co-administration Propanolol and chlorpromazine mutually inhibit each other s hepatic metabolism. Haloperidol inhibits CYP2D6-mediated metabolism of propanolol and timolol Watch for toxic effects of chlorpromazine and propranolol 1 doses accordingly... 

A 40-year-old woman developed agranulocytosis after taking risperidone for 2 weeks (114). She had also developed agranulocytosis after treatment with several other antipsychotic drugs (chlorpromazine, haloperidol, and zuclopenthixol). 

Chlorpromazine, haloperidol, and other phenothiazine and butyrophenone neuroleptics produce significant blockade of both a and D2 receptors (see Chapter 18). 

ANTICOAGULANTS - ORAL 5. ANTIDEPRESSANTS - mianserin, paroxetine 6. ANTIDIABETIC DRUGS - repaglinide, sulphonylureas 7. ANTIEMETICS - aprepi-tant 5-HT3-antagonists 8. ANTIFUN-GALS - fluconazole, itraconazole, ketoconazole, voriconazole 9. ANTIPSY-CHOTICS - apiprazole, chlorpromazine, haloperidol 10. BETA-BLOCKERS-metoprolol, propanolol, timolol... 

Treatment of schizophrenia with typical neuroleptics like for instance chlorpromazine, haloperidol or fluphenazine has a beneficial effect on the positive symptoms of schizophrenia (delusions, hallucinations and positive thought disturbances) but little effect on the negative symptoms (social withdrawal, blunted affect and apathy). 

Chloroquine, halofantrine, quinine Chlorpromazine, haloperidol, flufenazine, lithium, mesoridazine, pimozide, prochlorperazine, roperidol, sultopride, sertindole, risjreridone, thioridazine, trifluoperazine... 

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