Neuroleptics haloperidol

Other drugs such as the neuroleptic, haloperidol, inhibit the induction of hsp70 mRNA in rodent neurons (Sharp et al.. 1992). Although this observation needs to be confirmed in the human population, it raises the possibility that an age-dependent defect in the production of HS proteins is exacerbated by a drug which is commonly used in demented elderly patients. The potential for certain pharmacologic agents to inhibit the HS response could increase the risk for untoward effects of atherosclerosis and hypoxia. A similar concern may be raised with certain calcium channel blockers which also have been found to reduce the synthesis of HS proteins in cardiac myocytes (Low-Friedrich and Schoeppe, 1991). 

Most psychotic and non-compliant patients are difficult to treat with lithium alone and need to be treated with neuroleptics. Haloperidol has been widely... 

CYP1A2 Antidepressants amitriptyline, clomipramine, imipramine, fluvoxamine Neuroleptics haloperidol, phenothiazines, thiothixene, clozapine, olanzapine Others tacrine, caffeine, theophylline, acetaminophen, phenacetin No report of polymorphism until 1999 significance of following findings remains unclear 1C reduced activity 23% in Japanese 1F higher inducibility 32% in Caucasians... 

Ishizaki T, Chiba K, Saito M, Kobayashi K, lizuka R. The effects of neuroleptics (haloperidol and chlorpromazine) on the pharmacokinetics of valproic acid in schizophrenic patients. J Clin Psychopharmacol (1984) 4, 254-61. 

Antagonists of catecholaminergic function have also been used. The neuroleptics haloperidol (a centrally acting butyrophenone) and (- )sulpiride have been administered to lead-dosed animals. Lucchi etal. (1981) found that rats dosed with 2.5 g Pb/1 (1365 ppm Pb) showed no differences in halo-peridol-induced sedation, while the dose of (-)sulpiride which caused sedation was lower in lead-intoxicated animals than in control rats. These observations suggest that one of the neurochemical changes that may be ascribed to lead is an alteration in receptors sensitive to (-)sulpiride, i.e. a discrete population of dopaminergic D2 receptors. 

Singh, M. M. and Kay, S. R. (1975) A longitudinal therapeutic comparison between two prototypic neuroleptics (haloperidol and chlor-promazine) in matched groups of schizophrenics. Non therapeutic interactions with trihexyphenidyl. Theoretical implications for potency differences. Psychopharmacologia (Berl.), 43,115. 

The role of fluonne in the development of CNS agents has been reviewed [14] Ruonnated phenothiazines, typified by fluphenazine (7[Pg.1121]

Patients seen for flashbacks are treated with oral diazepam (15—30 mg/day for adults) if symptoms of anxiety are severe (Rumack 1987). Neuroleptics, especially haloperidol, have been implicated in a transient increase in visual flashbacks and are not recommended (Moskowitz 1971 Strassman 1984). Risperidone and selective serotonin reuptake inhibitors may also worsen symptoms of hallucinogen persisting perception disorder (Halpern and Pope 2003). The patient needs assurance of the self-limiting nature of the phenomenon and its decreasing frequency of reoccurrence with time. The patient should be reminded that any future use of hallucinogens or marijuana may precipitate similar symptoms (Strassman 1984). 

DA neurons in this nucleus, that not all the effects are elicited by the release of DA. Most neuroleptics block the inhibitory effects of applied DA but some, e.g. haloperidol, are less active against SN-evoked inhibition. Generally these studies lacked specific agonists and antagonists used microintophoresis which is not really quantitative and with extracellular recording gave little information on the state of polarisation of the neuron. 

Figure 17.8 Comparison of the antagonist potencies of some neuroleptics on different NT receptors. Data are shown for haloperidol (HAL), chlorpromazine (CPZ), clozapine (CLOZ) and risperidone (RISP) acting on dopamine Dj and D2, 5-HT2 (S2), alpha (0(2) adrenoceptors and cholinergic muscarinic receptors (M). The height of each column shows an average of the dissociation constants obtained from a number of publications (see Seeman 1990). The values, which can vary some fiftyfold, are expressed as the negative logarithms (i.e. 9 = 10 M,lnM) so that the higher the column, the more potent the compound. The order of potency of the four compounds at each receptor is shown alongside...

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. 

The close resemblance between schizophrenia and PCP-induced psychosis suggests that the behavioral effects produced by PCP might be useful as a model of psychosis. On this basis, most animal studies have examined the ability of various agents to modify PCP-induced hyperactivity and stereotypy. While some studies suggest that neuroleptics such as haloperidol (Castellani and Adams 1981 Garey et al. 1980), chlorpromazine, or clozapine (Freed et al. 

The patient may be alert and oriented, withdrawn or lethargic, or have an acute brain syndrome. There is a high incidence of rhabdomyolysis and hyperthermia in PCP-induced catatonic syndrome. Some patients have the neuroleptic malignant syndrome or develop it after administration of haloperidol. 

Chlorpromazine is technically described as a phenothiazine, as are thioridazine and fluphenazine. Together with their structural analogues the thioxanthenes (e.g., clopenthixol) and the butyrophenones (e.g., haloperidol), the phenothiazines comprise the three major families of typical neuroleptics. They were developed in the late 1950s and early 1960s (Table 11.3). All these drugs block dopamine receptors, principally the D2 subtypes, with an affinity that correlates highly (r = +0.90) with their clinical... 

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