Haloperidol reduced

Chlorpromazine, thioridazine, perphenazine, haloperidol, reduced haloperidol, risperidone, clozapine, sertindole Others... 

Several double-blind studies have demonstrated that typical agents are effective in decreasing problematic behaviors in children with DD. For example, haloperidol reduced anger, hyperactivity, and stereotypies (Campbell et al., 1979) in the dose range of 0.25-4 mg/day. Pimozide reduced problematic behaviors in children with PDD (Naruse et al., 1982). However, the possible long-term side effect of tardive dyskinesia remains a concern when using these agents. 

Risinger FO, Dickinson SO, Cunningham CL (1992) Haloperidol reduces ethanol-induced motor activity stimulation but not conditioned piace preference. Psychopharmacol 107 452-456. 

CYP2D6 Antidepressants amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, N-desmethyl-clomipramine, fluoxetine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics chlorpromazine, thioridazine, perphenazine, haloperidol, reduced haloperidol, risperidone, clozapine, sertindole Others codeine, opiate, propranolol, dextromethorphan 4 no activity 25% in Caucasians 0%-10% in others 5 no activity 2%-10% in all groups 10 reduced activity 47%-70% in Asians <5% in others 17 reduced activity 25%-40% in blacks 0% in others 2XN increased activity 19%-29% in Arabs and Ethiopians <5% in others... 

Haloperidol reduces the metabolism of the tricyclic antidepressants, thereby reducing their clearance, which results in a rise in their plasma levels. 

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). 

There are few reports on the effects of nitrous oxide on dopaminergic neurotransmission. A study in mice showed that nitrous oxide inhalation produced a significant increase in locomotor activity that was antagonized in a dose-dependent fashion by the dopamine synthesis inhibitor a-methyl-/)-tyrosine (Hynes and Berkowitz 1983). Moreover, administration of the D2 antagonist haloperidol also reduced the locomotor activity induced by nitrous oxide (Hynes and Berkowitz 1983). These results suggest that excitatory effects induced by nitrous oxide may be also mediated by dopaminergic neurotransmission. However, other studies have reported that exposure to nitrous oxide resulted in decreased dopamine release by neurons in the striatum (Balon et al. 2002 Turle et al. 1998). 

Only two randomized, controlled trials have been completed, and neither provides anything like compelling data (Table 2.6). Chouinard and Albright (1997) conducted a unique evaluation of a subset of patients from a previously conducted clinical trial. Subjects were categorized and profiled at baseline and end point according to clinical severity, and a group of psychiatric nurses were asked to rate various aspects of likely outcome and quality of life to each profile (mild, moderate or severe symptoms). Health state utilities were then calculated risperidone was found to provide more than double the number of quality-adjusted life years compared with haloperidol. Csernansky and Okamoto (1999) conducted a rather more conventional trial, but included no economic analyses. However, they did find that the use of risperidone substantially reduced relapse rates compared with haloperidol—an outcome likely to have a positive impact on cost-effectiveness. 

In view of the known cellular actions of DA, such as increased K+ efflux and reduced Ca + currents associated with Dj receptor activation in cell lines, inhibition would be the expected response to DA, especially as cyclic AMP, which is increased by Dj receptor activation also inhibits striatal neurons. In fact although many DA synaptic effects are blocked by Dj antagonists like haloperidol, the role of Di receptors should not be overlooked. 

Another indication of the importance of DA in motor control is the observation that in humans its precursor levodopa, and DA agonists like bromocriptine, not only overcome the akinesia of Parkinsonism but in excess will actually cause involuntary movements, or dyskinesia (Chapter 14). Also it is well known that DA antagonists like chlorpromazine and haloperidol produce Parkinsonian-like symptoms in humans (and catalepsy in animals) and, as indicated above, reduce the dyskinesia of Huntington s Chorea. Thus DA seems to sit on a knife edge in the control of motor function (Fig. 7.8). 

K (nM) values for clozapine at D2 and Di receptors are 56 and 141 compared with 0.5 and 27 for haloperidol giving D1/D2 ratios of 2.5 and 54 for the two drugs. A relatively strong block of Di compared with D2 receptors may not be the answer for schizophrenia but it could reduce the tendency to produce dyskinesias, if this depends on Di receptor activation (see Fig. 17.2). 

Jann, M. W. et al. (1989). Haloperidol and reduced haloperidol plasma levels in Chinese vs. non-Chinese psychiatric patients. Psychiatry Res., 30, 45-52. 

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

FIGURE 58-7 The IC50 values (ordinate) are the concentrations of the antipsychotic drugs that reduce the stereospecific component of 3H-haloperidol binding by 50%. The abscissa indicates the average values (and ranges) of doses used for schizophrenia. (From Seeman, P. et al. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261 717-719,1976)... 

Haloperidol Haloperidol 40-70 12-36 21 days CYP1A2, CYP2D6, CYP3A4 Reduced haloperidol... 

Conversion of haloperidol to reduced haloperidol (a secondary alcohol) Glutathine dependent reduction of disulfiram to deithyldithiocarbamate Thioredoxin dependent of sulindac to sulindac sulfide DT diaphorase reduction of menadione to hydroquinone Conversion of pentabromoethane to tetra bromoethane (releasing free bromide ion)... 

Behavioral and emotional effects In animal studies, ginseng does not prolong pentobarbital-induced sleep, nor does it affect spontaneous locomotion (Mitra et al. 1996). It does potentiate amphetamine-induced locomotion, but it reduces the stereotypy and lethality caused by amphetamine. Ginseng has analgesic effects, which are discussed at greater length in chapter 8. Catalepsy induced by haloperidol is potentiated by ginseng, while the hyperthermic effect of 5-HTP is attenuated. No antiseizure effects have been observed. 

There is another reason why medications exert multiple effects. For example, an antidepressant that very specifically promotes serotonin neurotransmission and has little or no interaction with other receptor types will still produce multiple effects. How can this be Remember that in different areas of the brain, a single neurotransmitter can assume very distinct roles. When an individual takes a medication that alters the activity of a particular neurotransmitter, it generally does so throughout the brain. Consequently, the dopamine receptor blocking effect of haloperidol (Haldol) reduces hallucinations and paranoia in one brain region but causes upper extremity stiffness through its action in another brain region. 

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