• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.114-121
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• 1998

Bethanechol, a cholinergic agonist, has been recommended for the management of peripheral anticholinergic side effects during the treatment of antipsychotic medications. But there have been few studies which have evaluated the drug interactions of antipsychotics and bethanechol, even the treatment effects of bethanechol on anticholinergic side effects. So the authors have evaluated whether psychopathology and plasma haloperidol and reduced haloperidol concentrations are significantly changed or not when bethanechol was administrated with maintained doses of haloperidol and other coadministrated drugs(such a benztropine). Also we have evaluated the abating effects of bethanechol on anticholinergic side effects during the treatment with haloperidol. Fifteen schizophrenics with higher than 5 of total score of anticholinergic side effects of 'Rating scale for side effect' were assigned to two groups, and bethanechol 30mg/day and 60mg/day were applied on each group for 4 weeks. The daily haloperidol dosages were fixed before 2 weeks of study. We assessed anticholinergic side effects by 'Rating scale for side effect' and psychopathology by BPRS, and plasma haloperidol and reduced haloperidol concentrations by HPLC at baseline, 2nd week and 4th week. The results were as followed, 1) there was no significant change of plasma haloperidol and reduced haloperidol concentration, 2) at baseline, the dosage of haloperidol showed significant correlation with the total score of anticholinergic side effect, but not at 2nd week and 4th week, 3) in 60mg/day group, dry mouth and the total score of anticholinergic side effects were significantly improved, but not in 30mg/day group, 4) there was no significant change of BPRS except withdrawal at 2nd week. These results suggest that coadministration of bethanechol influenced neither on psychopathology nor on plasma haloperidol and reduced haloperidol concentrations and that improved dry mouth and total score of anticholinergic side effects at 60mg/day.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.251-257
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• 1996

Selective serotonin reuptake inhibitors(SSRIs), as haloperidol, ore metabolized in the cytochrome P450IID6. They can cause inhibition of metabolism of antipsychotics to elevate the serum level of antipsychotics and exacerbate the extrapyramidal symptoms when co-administered with antipsychotics. Among these SSRIs, there ore a few studies about paroxetine compared to fluoxetine or sertraline. In this study, we have intended to know the drug interaction of paroxetine and haloperidol when co-administered two drugs for the chronic schizophrenics by assessing the changes of positive, negative symptoms and extrapyramidal symptoms. for this purpose, we selected 29 subjects, the chronic schizophrenics with no physical problems. They were under maintenance therapy of haloperidol. They ore randomly assigned to placebo group(n=12) and drug group(n=17) by using double blind method. And then, placebo or paroxetine 20mg were administered to the subjects of each groups during 8 week period. We have assessed their psychopathology and extrapyramidal symptoms using Positive and Negative Syndrome Scale(PANSS), Hamilton Rating Scale lor Depression(HRSD), Simpson-Angus Scale at 0, 2, 4, 6, 8 weeks and serum haloperidol, reduced haloperidol levels at 0, 4, 8 weeks during the period. The results ore analysed by using repeated measure MANOVA. 27 subjects have completed the study during 8 weeks. among the subjects, 1) PANSS, HRSD ; no significant difference between groups. 2) Simpson-Angus Scale ; no significant change according to the time and no significant difference between the groups(no group and time effect). 3) Haloperidol and reduced haloperidol level ; no significant change. When co-administered paroxetine and haloperidol, there ore no significant changes of the psychopothology and no significant changes of the extrapyramidal symptoms. In this result, paroxetine seems to be not to affect the metabolism of haloperidol.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.197-204
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• 1992

A gas chromatographic method using nitrogen phosphorous selective detection was developed for simultaneous determination of haloperidol and its metabolite, reduced haloperidol, in human plasma. Combelen was used as internal standard, The method involved extraction and trimethylsilylation followed by the injection of $2-4\;{\mu}l$ of benzene layer, which was used to dissolve the trimethylsilylated derivatives of haloperidol and reduced haloperidol, onto SE-54 column [5% phenyl methyl silica fused capillary column, $16m{\times}0.22\;mm$ $(I.D.){\times}0.33\;{\mu}m$ (coated thickness)]. The temperature of column oven was programmed from $200^{\circ}C\;to\;300^{\circ}C$ at the increase rate of $10^{\circ}C/min and also the temperatures of injector and detector were set at $300^{\circ}C$. Helium was used as carrier gas and its flow rate was maintained at 30 ml/min. The detection was conducted with nitrogen phosphorous selective detector. The retention times for combelen, reduced haloperidol and haloperidol were found to be 9.14, 9.75 and 9.99 min, respectively. The detection limits for haloperidol and reduced haloperidol in human plasma were both 0.2 ng/ml. The coefficients of variation of the intra-assay were generally low (below 9.8%). The mean absolute recoveries of added haloperidol and reduced haloperidol from plasma were 72% and 84%, respectively. No interferences from endogenous substances were found.

• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.19-27
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• 1975

Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.240-244
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• 1996

The effects of chronic treatment with haloperidol on the binding capacities of dopamine(DA) $D_2$-like receptor were investigated in rat striatum and olfactory tubercle. The authors tried to confirm the dose-response effects with usual dose and low dose haloperidol. Rats were treated with haloperidol(0.05, 0.15, 0.5, 1.5mg/kg/day in drinking water) for four weeks. Saturation analysis of the binding of [$^3H$]spiperone to striatal membranes showed that the haloperidol treatment(0.05, 0.5, 1.5mg/kg) induced significant proliferation. The changes of dissociation constant(Kd) were not significant in striatum. The maximal binding density(Bmax) and Kd increased remarkably following the treatment with usual dose haloperidol (1.5mg/kg) in olfactory tubercle. Although there was increasing trend other the treatment with low dose haloperidol, the change of Bmax was not significant statistically. The present findings indicate that low dose haloperidol induces the proliferation of DA $D_2$-like receptor in striatum and interact with the dopaminergic transmission which might underlie the antipsychotic effect. This finding may support the recent clinical suggestion on the low dose strategy in the treatment of schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.74-79
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• 2000

Objectives : The dopamine-blocking effects and the associated side effects(amenorrhea, lactation, sexual dysfunction) of classical antipsychotics in schizophrenic patients have been studied for a long time. The purpose of this study was to find out these effects of new antipsychotics(risperidone, olanzapine) in schizophrenic patients treated with clinically relevant doses. Method : Plasma levels of both prolactin and testosterone were measured in 91 schizophrenic patients(28 taking haloperidol, 4-20mg/day ; 31 taking risperidone, 2-6mg/day ; 32 taking olanzapine, 5-20mg/day). Results : In male schizophrenic patients, the prolactin levels of risperidone group($76.44{\pm}38.85ng/ml$) and haloperidol group($60.26{\pm}20.74ng/ml$) had no significant difference, but were significantly higher than that of olanzapine($26.90{\pm}5.36ng/ml$). In female, the prolactin level of olanzapine group($36.66{\pm}17.55$) was significantly lower than those of risperidone($121.7{\pm}48.33$) and haloperidol group($161.66{\pm}37.53$). And prolactin level of risperidone group was lower than that of haloperidol group. While the testosterone plasma level of risperidone, haloperidol and olanzapine in both male and female schizophrenic patients had no significant difference. Conclusions : At doses known to be effective in popular clinical setting, prolactin level in patients taking risperidone was higher than that of haloperidol, while olanzapine showed no significant difference in terms of prolactin plasma level from haloperidol. New antipsychotics may not influence the testosterone plasma level.

• Korean Journal of Psychosomatic Medicine
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• v.13 no.2
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• pp.85-94
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• 2005

Objectives: This prospective and open-label study was conducted to evaluate the efficacy and safety of quetiapine and haloperidol in patients with delirium. Methods : Fourty patients(19 patients in a quetiapine group : 21 patients in a haloperidol group) with delirium by DSM-IV were treated with flexible doses of open-label qvetiapine and haloperidol. To evaluate the primary efficacy of the medication, scores from the Korean version of Delirium Rating Scale(K-DRS) were assessed every seven days and to evaluate the secondary efficacy and safety, scores from the Clinical Global Impression-Severity, Korean Version of Mini-Mental State Examination, and the Drug-Induced Extrapyramidal Symptoms Scale were assessed at the baseline and the seventh day. Data were gathered from November 2004 to June 2005. Results : K-DRS scores for each group decreased significantly over the study period; however, no significant differences between groups were found. The group-by-time effect was not significant. In addition, there was no significant difference in the frequency of response to drugs between the two groups. No patients reported clinically significant side effects. Conclusion : These data show no significant difference in the efficacy and safety between quetiapine and haloperidol in the treatment of delirium. Since haloperidol has a great possibility of causing a extrapyramidal side effect resulted by previous studies, it is expected that quetiapine, a renowned medication with low side effects, may be a useful alternative agent to haloperidol, the classical antipsy-chotics, in the treatment of delirium.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.127-135
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• 2004

Object:The goal of this study was to examine the changes in body weight and glucose levels of the patients treated with risperidone, clozapine or haloperidol in order to compare the effect of risperidone or clozapine with that of haloperidol. Methods:For nine months(January to September, 2003), a prospective study was performed in 60 patients with chronic schizophrenia who were in Seoul National Hospital. Two-week period was required for a drug wash-out. The patients were randomly assigned to risperidone, clozapine and haloperidol groups. They were given risperidone(n=20), clozapine(n=20) and haloperidol(n=20), respectively, everyday for 12 weeks. To examine the effects of these drugs on body weight and fasting glucose levels, we measured body weight and glucose levels of all the patients first without the drug treatment and at each end of 4, 8, and 12-week periods with the treatment. And we examined the differences among three groups in the changes of body weight and fasting glucose levels. Results:There were no significant differences in the changes of the body weight and fasting glucose levels between the atypical antipsychotics(risperidone or clozapine) and the typical antipsychotics(haloperidol). Conclusion:The study in the patients with chronic schizophrenia suggests that risperidone or clozapine do not cause any additional effects on body weight or glucose levels compared to haloperidol.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.11-18
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• 1994

Cyclic adenosine 3'5'-monophosphate (cyclic AMP) has been frequently accepted as an intracellular messenger for receptor-mediated action of opioids. In this experiment, it was designed to determine the interaction of dopaminergic and opioidergic system in the mouse striatum in normal and chronic haloperidol treated groups. Haloperidol 750ug/kg I.P. for 10 days was performed for dopamine denervation. The morphine, DAGO, DPDPE, and U5O,488H inhibited the increase of haloperidol-induced cyclic AMP content in chronic haloperidol treated mouse striatum. The inhibition of DAGO and DPDPE showed significant increase compared to normal mouse striatum. Naloxone showed antagonistic effect on the morphine and U5O,488H in chronic haloperidol treated group, and showed antagonistic effect on morphine, DAGO, DPDPE, and U5O, 488H in normal mouse striatum. These findings support that there is a functional interrelationship of dopaminergic and opioidergic pathway in the striatum. This result provides an evidence that following destruction of striatal dopaminergic neuron, there are some changes of cAMP content on the ${\mu},\;{\gamma},\;and\;{\kappa}$ opioid receptor, but the ${\kappa}$ opioid receptor still has its function.

• Journal of Ginseng Research
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• v.16 no.1
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• pp.18-23
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• 1992

Central dopaminergic activity of standardized ginseng extract G115 was investigated in comparison with those induced by haloperidol in rats. The effects of G115 on the locomotor activity and, stereotyped behavior induced by apomorphine, which interacts directly with dopamine receptor were observed. Apomorphine(2 mg/kg) significantly decreased locomotor activity, whereas it showed a markdly increased incidence of stereotyped behavior. Standardized ginseng extract G115(100 mg/kg) and haloperidol(1 mg/kg) showed a significant decrease in locomotor activity but not induced stereotyped hehavior. Locomotor activity induced by apomorphine was markdly decreased by haloperidol(1 mg/kg), but that was significantly increased by standardized ginseng extract G115(50 mg/kg). Stereotyped behavior induced by apomorphine was completely supressed haloperidol(1 mg/kg), but was not changed by standardized ginseng extract G115. These results suggest that standardized ginseng extract G115 plays an important role in central dopaminergic activity, and haloperidol and standardized ginseng extract G115 seem to have a different action in behavior.