Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Haloperidol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed1989

Clinical implications of determination of plasma haloperidol levels.

The aim of this study was to analyze the clinical utility of monitoring plasma levels, since the utility of monitoring is not yet well established. After a washout period, 30 schizophrenic patients were given fixed doses of haloperidol for 3 weeks. A U-shaped second-grade polynomic relationship (R = 0.69) was found between steady state of haloperidol and percentage improvement in total score on the Brief Psychiatric Rating Scale. The interval of effective concentrations was between 12 and 59 ng/ml. Fourteen of the 15 patients who had a steady state of haloperidol within that therapeutic interval were responders: only 5 out of the 15 patients below the therapeutic interval were responders. None of the 5 patients who had concentrations below 8 ng/ml was a responder. Furthermore, responder patients showed a steady-state level of haloperidol significantly higher than that of nonresponders. These data suggest that plasma levels of haloperidol are predictors of therapeutic response in schizophrenic disorders.

Adult↗
PubMed1990

A double-blind multicentre comparison of remoxipride, at two dose levels, and haloperidol.

A total of 186 patients who met the DSM-III criteria for schizophrenia were admitted to a double-blind randomized multicentre trial in which the efficacy and safety of remoxipride at two dose levels was compared with those of haloperidol. Over a period of six weeks the patients received remoxipride 100-300 mg/day (n = 60), remoxipride 200-600 mg/day (n = 61), or haloperidol 10-30 mg/day (n = 64). There was no significant difference between the three treated groups with regard to the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores obtained. Remoxipride, at both dosage ranges used, thus had comparable therapeutic efficacy to that of haloperidol. In contrast, extrapyramidal symptoms occurred significantly more frequently in the group treated with haloperidol. Laboratory tests and cardiovascular investigations showed no specific drug effect in any of the treated patients. Remoxipride is thus effective in acute treatment of schizophrenia at both dosage levels and has an advantage over haloperidol in neurological acceptability.

Adolescent↗
PubMed1990

A double-blind comparative study of remoxipride and haloperidol in acute schizophrenia.

Seventy-one patients were entered into a multicentre, double-blind randomized study to compare the efficacy and safety of remoxipride with those of haloperidol in the acute treatment of schizophrenia or schizophreniform disorder. The patients, who were well-matched regarding demographic characteristics, were aged 18-64 years. Four patients in the remoxipride group and 6 in the haloperidol group discontinued treatment prematurely. The mean daily doses during the last week of treatment were 363 mg remoxipride and 9 mg haloperidol. At this time 22% of patients on remoxipride and 66% of those on haloperidol were taking anticholinergics (p less than 0.001). The clinical efficacy was similar in both groups as judged by Present State Examination (PSE) profile and Brief Psychiatric Rating Scale (BPRS) ratings. Several adverse symptoms occurred significantly more frequently during treatment with haloperidol than with remoxipride, particularly where extrapyramidal symptoms were concerned. No clinically relevant changes occurred in the laboratory tests in either group.

Acute Disease↗
PubMed1990

Remoxipride and haloperidol in the acute phase of schizophrenia: a double-blind comparison.

The efficacy and safety of remoxipride in the treatment of schizophrenia were compared with those of haloperidol in a multicentre double-blind 6-week study which was randomized with a parallel group design and was preceded by a washout period. Eighty-nine consecutively admitted men and women meeting the Research Diagnostic Criteria for schizophrenia in an acute phase of the illness were treated with remoxipride 75-300 mg twice daily or haloperidol 5-20 mg twice daily. The efficacy assessments were the Brief Psychiatric Rating Scale, Krawiecka Rating Scale, and Clinical Global Impression. Both antipsychotic drugs produced clinical improvement with no significant differences between the efficacy of the two drugs. There were relatively few side effects. There were significantly fewer extrapyramidal symptoms and instances of blurred vision with remoxipride and less constipation with haloperidol. The results indicate that remoxipride is as effective an antipsychotic as haloperidol. Remoxipride has an advantage over haloperidol in respect to extrapyramidal side effects.

Acute Disease↗
PubMed1990

A double-blind multicentre study comparing remoxipride, controlled release formulation, with haloperidol in schizophrenia.

A double-blind multicentre study was undertaken to compare the efficacy and safety of remoxipride in a controlled release (CR) formulation given once daily with haloperidol twice daily in patients with schizophrenic illness. In total, 114 patients were included. All were diagnosed as schizophrenic or schizophreniform according to DSM-III. Their mean daily dose of remoxipride CR during the last week of treatment was 385 mg. In the haloperidol group the corresponding dose was 17 mg per day. The intended study period was 4 weeks with at least a one-day washout. No significant differences were found between treatments regarding efficacy variables. The median total Brief Psychiatric Rating Scale (BPRS) score was 40 in the remoxipride CR group at start of treatment and 21 at last valid rating. For the haloperidol group the corresponding figures were 40 and 22. Treatment-emergent extrapyramidal symptoms (Simpson and Angus rating) occurred statistically significantly more frequently and were more severe during haloperidol than during remoxipride CR treatment despite a statistically significantly higher concurrent use of anticholinergic drugs in the haloperidol group.

Acute Disease↗
PubMed1998

Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol.

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P < 0.03). Conjugated HVA levels slowly decreased during the following weeks (P < 0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P < 0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

Adult↗
PubMed1997

Undernutrition during suckling changes the sensitivity to haloperidol and chlorpromazine in two behavioural measures in weaning rats.

Undernutrition during critical periods of development may cause changes in the behavioural responses of rats to centrally acting drugs. In the present study, the effects of undernutrition during suckling on the behavioural responses of 21-days-old rats to chlorpromazine (0, 2.5, 5, 10 and 20 mg/kg) or haloperidol (0, 0.125, 0.25, 0.5, 1 or 2 mg/kg) were examined. Locomotion was assessed at 1 hr 30 min., 4 hr 30 min., 7 hr 30 min, and 10 hr 30 min., and catalepsy was scored at 3 hr, 6 hr and 9 hr after drug administration. Drug was injected on two consecutive days. On day 1, saline-treated undernourished rats showed significantly greater locomotion activity than did normal rats. The neuroleptic-induced inhibition of locomotor activity in undernourished rats was significantly less than that observed in normal rats from 4 hr 30 min. to 10 hr 30 min. (chlorpromazine) or from 7 hr 30 min. to 10 hr 30 min. (haloperidol). On day 2, a similar trend was observed but only in rats injected with 5 mg/kg chlorpromazine or 0.5, 1, and 2 mg/kg haloperidol. On day 1, the catalepsy scores at 3 hr revealed no significant difference between nutritional groups, but at 6 hr undernourished rats responded significantly less to chlorpromazine or haloperidol. On day 2, undernourished rats were less responsive to neuroleptics than normal rats, but the effect was not so evident as observed on day 1. The present results suggest that the behavioural effects of chlorpromazine and haloperidol are less persistent in undernourished rats, possibly due to differences in drug distribution and elimination, when compared to well-nourished rats.

Analysis of Variance↗
PubMed1993

Acute accidental overdosage of haloperidol in children.

We report the details of an accidental overdosage of haloperidol in 24 children in one hospital in Kyushu, Japan. Evidence of acute toxicity included disturbances in consciousness (24/24), tremors in the extremities (16/24), an oculogyric or similar crisis (14/24), dysarthria (9/17), drooling (8/24), akathisia (6/20), hyperreflexia (6/24) and opisthotonos (3/24). Laboratory examinations revealed late-onset transient thrombocytosis (5/24), elevated AST and GPT (1/24) and abnormal ECG with prolonged QT interval in 2 of 8 children. We detected haloperidol in 11 of 18 children whose blood was specifically examined within four days after the final haloperidol administration. The maximum serum haloperidol level was 28.9 ng/ml. The mean half-life of haloperidol in the serum of five children (age range 2-10 years) was 18.6 +/- 12.2 h (mean +/- SD) (range 9.1-39.4 h).

Acute Disease↗
PubMed1988

Definition of the in-vivo accumulation of [3H]spiperone in brain using haloperidol and sulpiride to determine functional dopamine receptor occupation.

The in-vivo administration of [3H]spiperone caused an accumulation of radioactivity in the substantia nigra, tuberculum olfactorium, nucleus accumbens, striatum and frontal cortex when compared with cerebellar levels. Haloperidol (0.01-1.0 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone in the substantia nigra, tuberculum olfactorium, striatum and nucleus accumbens. Sulpiride (10-160 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone only in the substantia nigra. The effects of sulpiride on other areas were not consistent; there was a suggestion of a reduction in the accumulation of [3H]spiperone in tuberculum olfactorium and striatum, but not in nucleus accumbens. Neither haloperidol (0.01-1.0 mg kg-1 i.p.) nor sulpiride (10-160 mg kg-1 i.p.) caused displacement of [3H]spiperone from the frontal cortex. Both haloperidol (0.01-0.5 mg kg-1) and sulpiride (10-80 mg kg-1) increased striatal and mesolimbic HVA concentrations. Haloperidol potently blocked apomorphine-induced stereotypy but sulpiride was only effective at the highest dose employed. The functional effect produced by haloperidol correlated with its ability to define [3H]spiperone binding in-vivo to dopamine receptors in the substantia nigra, striatum and tuberculum olfactorium. In contrast, there was no correlation between functional effect of sulpiride and its ability to define [3H]spiperone binding in-vivo.

Animals↗
PubMed1990

A pharmacodynamic model to predict the time dependent adaptation of dopaminergic activity during constant concentrations of haloperidol.

The concentration-response relationship of the accumulation of brain homovanillic acid (HVA) has been studied by giving rats a shorter (12 h) and a longer (76 h) constant intravenous infusion of haloperidol, respectively, at rates aiming at different steady state blood concentrations of haloperidol of 5 to 30 ng mL-1. The observed response on brain HVA concentration vs increasing steady state blood concentration of the drug produced a bell-shaped type of curve during the 12 h infusion. When the infusion proceeded for 76 h a similar type of curve was obtained but it was shifted downwards compared with the 12 h infusion. The dopaminergic activity of the rat brain, as reflected by the HVA levels, therefore adapted to a lower activity during the prolonged exposure to haloperidol. To follow the time course of this adaptation, one steady state level of about 12 ng mL-1 was established and kept for 12, 28, 52 and 76 h. The result showed that the accumulation of brain HVA decreased over time compared with control animals given placebo. A pharmacodynamic model was set up to quantitatively describe the time-dependent adaptation of HVA accumulation in the whole rat brain during constant haloperidol administration. By fitting this model to all three sets of experimental data simultaneously, an adaptation half-time of about 38 h +/- 14 (s.d.) and a tolerance potency of about 7 ng mL-1 were obtained which could be used to calculate that, for example, at a constant blood level of 10 ng mL-1 haloperidol over 5 days the accumulation of brain HVA decreased by approximately 91% of the maximal decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatum.

The present study was designed to examine the properties of [3H]haloperidol binding to dopamine D2-receptors in rat striatum membranes, displacement potencies of various chemicals and differences between the affinities of various chemicals and two new 5-hydroxytryptamine (5-HT2) receptor antagonists, MCI-9042, (+/-)-2-(dimethylamino)-1-[[o-(m-methoxyphenetyl)phenoxy]methyl]et hyl hydrogen succinate hydrochloride and one of its metabolites. The plots of specific binding for the striatum membranes obtained from the Scatchard analysis using [3H]haloperidol were monophasic when non-specific binding was determined with 10 microM chlorpromazine, and the Kd and Bmax values were 7.42 +/- 1.03 nM and 1.58 +/- 0.20 pmol (mg protein)-1 (n = 10), respectively. The displacement potencies of D2 receptor, 5-HT2 receptor, histamine H1-receptor, and adrenoceptor antagonists were characterized by [3H]haloperidol binding to D2 receptors. The pKi values of a new antiplatelet agent, MCI-9042, and its metabolite were 5.02 and 5.53, respectively, and these values were lower than those of the D2-receptor antagonists, fluphenazine, spiperone, haloperidol, prochlorperazine, chlorpromazine, thioridazine, and sulpiride. They were also lower than the pKi values of the 5-HT2-receptor antagonists, pirenperone, ketanserin, methysergide, and mianserin. We conclude that the binding site of [3H]haloperidol in the rat striatum is the D2 receptor, that MCI-9042 and its metabolite have lower affinities for D2 receptors than for 5-HT2 receptors, and that this radioreceptor assay is useful for assessing the affinities of various agents.

Animals↗
PubMed2003

Chronic administration of haloperidol and olanzapine attenuates ketamine-induced brain metabolic activation.

The fact that chronic administration of typical and atypical antipsychotic drugs is required for optimal therapeutic response suggests that drug-induced adaptive neurochemical changes contribute to their mechanism of action. In the present study, the effects of chronic and acute haloperidol and olanzapine were compared on ketamine-induced activation of select brain regions, as reflected by altered regional 14C-2-deoxyglucose (2-DG) uptake. Rats were injected once daily with haloperidol (1 mg/kg) or olanzapine (10 mg/kg) for 21 days, and 20 to 24 h after the final injection was challenged with saline or ketamine (25 mg/kg). The washout period was used to test the effects of chronic drug treatment without the influence of acute drug administration. In vehicle-treated rats, ketamine increased 2-DG uptake in select brain regions, including medial prefrontal cortex, nucleus accumbens, caudate putamen, stratum lacunosum-moleculare of hippocampus, and basolateral nucleus of the amygdala. This selective activation was attenuated by prior chronic treatment with both haloperidol and olanzapine. After acute treatment, olanzapine, but not haloperidol, blocked the ketamine-induced activation of 2-DG uptake. These data suggest that both haloperidol and olanzapine can induce adaptive responses that counteract effects of ketamine. However, the differences observed in the acute effects of the two drugs in the ketamine challenge model suggest that different mechanisms could be responsible for their common chronic action of attenuating ketamine-induced brain metabolic activation.

Analgesics↗
PubMed2003

Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine.

OBJECTIVE: To compare two widely used drug treatments for people with aggression or agitation due to mental illness. DESIGN: Pragmatic, randomised clinical trial. SETTING: Three psychiatric emergency rooms in Rio de Janeiro, Brazil. SUBJECTS: 301 aggressive or agitated people. INTERVENTIONS: Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine. MAIN OUTCOME MEASURES: Patients tranquil or sedated at 20 minutes. SECONDARY OUTCOMES: patients tranquil or asleep by 40, 60, and 120 minutes; restrained or given extra drugs within 2 hours; severe adverse events; another episode of agitation or aggression; needing extra visits from doctor during first 24 hours; overall antipsychotic load in first 24 hours; and not discharged by two weeks. RESULTS: 151 patients were randomised to midazolam, and 150 to haloperidol-promethazine mix. Follow up for the primary outcome was available for 298 (99%): 134/151 (89%) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 (67%) of those given haloperidol plus promethazine (relative risk 1.32 (95% confidence interval 1.16 to 1.49)). By 40 minutes, midazolam still had a statistically and clinically significant 13% relative advantage (1.13 (1.01 to 1.26)). After 1 hour, about 90% of both groups were tranquil or asleep. One important adverse event occurred in each group: a patient given midazolam had transient respiratory depression, and one given haloperidol-promethazine had a grande mal seizure. CONCLUSIONS: Both treatments were effective. Midazolam was more rapidly sedating than haloperidol-promethazine, reducing the time people are exposed to aggression. Adverse effects and resources to deal with them should be considered in the choice of the treatment.

Adult↗
PubMed1977

Effects of antipsychotic drugs on action potential production in skeletal muscle. II. Haloperidol: nonspecific and opiate drug receptor mediated effects.

The effects of haloperidol, an antipsychotic butyrophenone, on excitability and action potential production in frog's sartorius muscle fibers were studied. This drug produced a local-anestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 X 10(-6 M) but was completely reversed by exposing the muscles to a drug-free solution. In studies with intracellular microelectrodes, evidence was obtained showing that haloperidol decreased excitability and depressed action potential production by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. Evidence also was obtained showing an inhibition of the secondary increase in potassium conductance (gK). Haloperidol is structurally related to meperidine and it was found that the inhibition of gNa produced by haloperidol is partially antagonized by low concentrations of naloxone (2.8 X 10(-8) and 2.8 X 10(-7) M); as was previously shown for meperidine. Thus haloperidol, like meperidine, suppresses action potential production by two mechanisms of action: one, a nonspecific local-anaestheticlike effect; and the other, a specific inhibition of gNa mediated by means of an opiate drug receptor associated with the muscle fiber membrane. Naloxone did not antagonize the effects of chlorpromazine on gNa.

Action Potentials↗
PubMed1989

Haloperidol reduction can be assayed in human red blood cells.

One metabolite of haloperidol present in plasma is "reduced haloperidol." This study demonstrates that human red blood cells are capable of converting haloperidol to reduced haloperidol in vitro. The reductase involved requires NADPH, as does haloperidol (ketone) reductase in human liver cytosol.

Adult↗
PubMed1997

Effects of haloperidol on ventilation during isocapnic hypoxia in humans.

Exposure to isocapnic hypoxia produces an abrupt increase in ventilation [acute hypoxic ventilatory response (AHVR)], which is followed by a subsequent decline [hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake, haloperidol has been reported to increase AHVR and almost entirely abolish HVD. To investigate whether this occurs in humans, the ventilatory responses of 15 healthy young volunteers to 20 min of isocapnic hypoxia (end-tidal PO2 = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) and after oral haloperidol (Seranace, 0.05 mg/kg) on different days. Three subjects were unable to complete the study because of akathisia. AHVR was significantly greater with haloperidol compared with control (P < 0.01, analysis of variance). However, no significant change in HVD was found [control HVD = 9.3 +/- 1.6 (SD) l/min, haloperidol HVD = 9.9 +/- 2.1 l/min; P = not significant, analysis of variance]. We conclude that combined central and peripheral dopamine-receptor antagonism in humans with haloperidol produces a similar pattern of change to that reported previously with the peripheral antagonist domperidone. We have been unable to show in humans a decrease in HVD by the centrally acting drug as observed in cats.

Adult↗
PubMedDate not supplied

Haloperidol attenuates beta-amyloid-induced calcium imbalance in human fibroblasts.

BACKGROUND: Antipsychotics are widely used in the treatment of behavioral and psychological symptoms of dementia. A low frequency of Alzheimer's disease in patients with schizophrenia is reported, and it has been proposed that antipsychotic medications, such as haloperidol, may be responsible. Disruption of intracellular calcium levels is considered to play a key role in beta-amyloid-induced neurotoxicity in Alzheimer's disease. Haloperidol has also been reported to interact with calcium homeostasis through dopamine-2 and sigma-1 receptors, and other, yet unknown mechanisms. OBJECTIVE: Therefore, we investigated whether differences in the basal intracellular free calcium levels of cultured cutaneous fibroblasts--cells that do not express dopamine-2 and sigma-1 receptors--derived from sporadic Alzheimer patients and from age-matched control individuals after haloperidol treatment might be present. METHODS: Intracellular calcium level was measured in Fura-2AM-loaded human fibroblasts by dual wavelength spectrofluorimetry. RESULTS: Alzheimer cells exhibited significantly lower calcium level as compared to the control cultures. Exposure of fibroblasts to beta-amyloid peptide resulted in increased calcium concentration of the control cells, but not of Alzheimer fibroblasts. Co-incubation of cultures with a therapeutic dose of haloperidol blocked the beta-amyloid-induced elevation of calcium. CONCLUSION: This finding indicates that haloperidol efficiently countervails ionic imbalance and suggests that it may serve as a potential agent in alleviating neurotoxic effects of beta-amyloid peptide.

Aged↗
PubMed1981

Suppression of amphetamine-induced EEG arousal in the hippocampus of haloperidol-treated rabbits.

Changes of hippocampal EEG activity resulting from administration of d-amphetamine were investigated in rabbits before, during and after chronic treatment with haloperidol. Cross-zero analysis of EEG data showed that chronic treatment with haloperidol (3 mg/kg/day, i.p. for 9 days) attenuated the amphetamine-induced increase in hippocampal theta rhythm. The increase of theta activity by amphetamine was fully restored 30 days after withdrawal of haloperidol. Further, haloperidol reduced the incidence of spontaneous theta rhythm in 3 out of 4 animals. It is suggested that the enhancement of hippocampal theta by d-amphetamine is mediated in part by dopaminergic mechanisms which are susceptible to the action of haloperidol.

Animals↗