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At least 73 records · Page 4Linked to original sources
PubMed1993

Resolution of the interference from carbamazepine and diphenhydramine during reversed-phase liquid chromatographic determination of haloperidol and reduced haloperidol.

Carbamazepine and diphenhydramine interfered with the assays of haloperidol and its metabolite, reduced haloperidol, by reversed-phase HPLC. Retention times of haloperidol, reduced haloperidol, and the interfering drugs were very sensitive to the percentage of potassium phosphate buffer in the mobile phase as well as to the final pH of the eluant. Retention times were not very dependent upon ionic strength of the eluting solvent mixture. Haloperidol and reduced haloperidol in the range of 0.5-10 ng/mL were analyzed in the presence of 0.2 micrograms/mL diphenhydramine and 5 micrograms/mL of carbamazepine. The concentrations of all drugs used were in their expected therapeutic ranges. The isocratic chromatographic conditions were as follows: 25-cm x 4.6-mm C-18 column; mobile phase, 75% phosphate buffer (final concentration, 0.06M) and 25% acetonitrile; final pH, 3.5; flow rate, 2.5 mL/min; and detection by UV absorption at 220 nm. Additional changes in the percent buffer in the mobile phase may be useful in achieving separation of other interfering compounds.

Buffers↗
PubMed1982

Tolerance and serum levels of haloperidol during parenteral and oral haloperidol treatment in geriatric patients.

Eleven geriatric chronic psychotic hospital patients were treated with monthly intramuscular haloperidol decanoate injections for 5 months. The first and second haloperidol decanoate dose was 20 times and thereafter 15 times the "optimal" oral haloperidol dose. The serum haloperidol concentrations were fairly stable during the whole month following parenteral administration. After the second and third injection the concentration was about twice as high as during oral treatment. No clinically significant changes were established in routine haematological or biochemical laboratory tests studied during the trial. No significant changes in serum prolactin levels were observed after parenteral haloperidol compared to the levels during oral treatment. No local or systemic side effects were observed during the trial. The psychiatric status of the patients was fairly constant during the whole study. Haloperidol decanoate was thus shown to be therapeutically effective and it can be administered safely to geriatric patients.

Administration, Oral↗
PubMed1992

Haloperidol and reduced haloperidol in saliva and blood.

A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment.

Adult↗
PubMed1995

Glutamate decarboxylase messenger RNA in rat pallidum: comparison of the effects of haloperidol, clozapine and combined haloperidol-scopolamine treatments.

We have investigated the effects of neuroleptic treatments which do, or do not, induce catalepsy on the level of expression of glutamate decarboxylase, the rate limiting enzyme in GABA synthesis, in efferent neurons of the pallidum in adult rats. Different regimens of haloperidol (1 mg/kg s.c., three, seven or 14 days; 2 mg/kg, s.c., 10 days) induced catalepsy in a majority of rats and increased glutamate decarboxylase messenger RNA levels in the globus pallidus (external pallidum) in those rats exhibiting catalepsy. Levels of glutamate decarboxylase messenger RNA were also increased in the entopeduncular nucleus (internal pallidum), but only after 14 days of treatment with haloperidol. The atypical antipsychotic clozapine (seven days, 20 mg/kg, s.c.), which did not induce catalepsy, slightly decreased glutamate decarboxylase messenger RNA levels in the globus pallidus. When co-administered with haloperidol (seven days, 1 mg/kg s.c.), the muscarinic antagonist scopolamine (1 mg/kg, s.c.) completely blocked both haloperidol-induced catalepsy and increases in glutamate decarboxylase messenger RNA levels in the globus pallidus. In contrast, scopolamine was not able to block increased glutamate decarboxylase and enkephalin messenger RNA expression induced by haloperidol in the striatum. These results reveal a good correlation between increases in glutamate decarboxylase messenger RNA levels in the globus pallidus and catalepsy after these drug treatments and suggest that anticholinergic blockade of the behavioral and molecular effects of neuroleptics may involve non-striatal mechanisms.

Animals↗
PubMed2000

The effect of serotonergic agents on haloperidol-induced striatal dopamine release in vivo: opposite role of 5-HT(2A) and 5-HT(2C) receptor subtypes and significance of the haloperidol dose used.

This study investigated, using microdialysis in freely-moving rats, the role of serotonin (5-HT) and 5-HT(2) receptor subtypes in the enhancement of striatal dopamine (DA) release induced by various doses of haloperidol. The subcutaneous injection of 0.01, 0.1 or 1 mg/kg haloperidol dose-dependently increased DA outflow (160, 219 and 230% of baseline, respectively). The effect of 0.01 mg/kg haloperidol was, respectively, potentiated by the 5-HT uptake inhibitor citalopram (1 mg/kg, s.c.; +35%) and reduced by the 5-HT(1A) receptor agonist 8-OH-DPAT (0.025 mg/kg, s.c.; -32%). Also, it was reduced by the 5-HT(2A) antagonist SR 46349B (0.5 mg/kg, s.c. ; -40%) or by the 5-HT(2A/2B/2C) antagonist ritanserin (1.25 mg/kg, i.p.; -34%), and potentiated by the 5-HT(2B/2C) antagonist SB 206553 (5 mg/kg, i.p; +78%). Further, only this latter compound significantly modified basal dopamine release by itself (+26%). Dopamine released by 0.1 mg/kg haloperidol was enhanced (+100%) by citalopram, decreased (-61%) by SR 4634B, but unaltered by SB 206553. Finally, none of the compounds used were able to modify the enhancement of dopamine release induced by 1 mg/kg haloperidol. These results show that central 5-HT(2A) and 5-HT(2C) receptors exert an opposite (respectively excitatory and inhibitory) influence on DA release. Moreover, they suggest that the 5-HT(2A)-dependent modulation depends on the degree of central DA receptor blockade.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Effect of different neuroleptics in tardive dyskinesia and parkinsonism. A video-controlled multicenter study with chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden. Nordic Dyskinesia Study Group.

Thirty-three chronic psychiatric patients with tardive dyskinesia (TD) were included in a video-controlled multicenter study of the effect of chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden in TD and parkinsonism. The drugs were given in a cross-over design in randomized order in dosages equipotent to the earlier neuroleptic treatment and administered for periods of 6 months with 6-week placebo periods before and after. A total of 55 treatment periods were completed; only seven patients were able to go through all three treatment phases (= 96 weeks). Perphenazine (20.5 mg/day), haloperidol (5.5 mg/day), and haloperidol (11 mg/day) + biperiden (7 mg/day) induced a moderate suppression of TD and at the same time produced a corresponding aggravation in parkinsonism. Chlorprothixene (142 mg/day) had only a slight TD reducing effect and did not change parkinsonism. Thus the TD suppressing effect was inversely related to the parkinsonian-inducing effect of the neuroleptics. Following withdrawal of the drugs, TD increased in some cases and decreased in others compared to the pretreatment level. No significant correlation was found between the intensity of the withdrawal TD and either drugs or preceding parkinsonism or TD suppression. Only in a subgroup of seven patients who consecutively received all three neuroleptics, perphenazine, but not haloperidol and chlorprothixene, produced a post-treatment aggravation which was correlated to the parkinsonsim and TD suppression during treatment. Independent of the neuroleptic given, the TD intensity increased significantly from the first to the third placebo period. This suggests that drug holidays are inappropriate to prevent TD induction/aggravation.

Adult↗
PubMed1982

Enhancement of avoidance-suppressing effect after repeated administration of haloperidol and serum haloperidol in rats.

Adult male rats of the Wistar strain, which were trained under a discriminated lever-press avoidance schedule (intertrial interval; 25 sec. presentation of conditioned stimuli; 5 sec), were given SC 0.025-0.05 mg/kg of haloperidol at fixed intervals of 1, 3-4 and 7 days. The avoidance-suppressing effect of haloperidol was enhanced in parallel to the number of drug administrations until it attained a maximum level. The intensity of the maximum effect tended to be stronger, and the number of administrations necessary to attain it was smaller, when a higher dose was given. When the administration interval exceeded one day, the enhanced effect remained irreversible one month after withdrawal of drug administration. The enhancement of the effect was produced after repeated administrations in an experimental chamber, but not in a home cage. Temporal changes in serum haloperidol concentration were determined 30-90 min after 0.035 mg/kg given SC to the haloperidol-pretreated and saline-pretreated groups. No significant difference in the pharmacokinetic change was detected between the two groups. These results suggest that learning during the drug effect under repeated exposure to a fixed experimental situation influences the enhancing effect.

Animals↗
PubMed1985

Quantification of reduced haloperidol and haloperidol by radioimmunoassay.

A radioimmunoassay for reduced haloperidol and haloperidol has been developed by using a simple derivatization-separation step prior to assay with an antibody cospecific for both compounds. The detection limit of the assay is less than 25 pg and shows no cross reactivity to other metabolites. The intraassay coefficient of variation for reduced haloperidol and haloperidol were 9.0 and 8.2% respectively and the interassay coefficients of variation were 9.0 and 10.6% respectively at 5-10 ng/ml. As many as 30 patient samples can be analyzed for both compounds in a single day.

Chromatography, Liquid↗
PubMed1981

Total and free serum haloperidol levels in schizophrenic patients and the effect of age thioridazine and fatty acid on haloperidol-serum protein binding in vitro.

1 Using radioimmunoassays, steady-state levels of total and free haloperidol (obtained by ultrafiltration and dialysis) have been determined in twenty-two patients on long term treatment receiving doses from 3 to 45 mg per day. 2 For the group, both total serum concentration and free drug concentration showed significant correlations (P less than 0.001) with daily dose. 3 No significant correlation was observed between age of the patient and percentage free haloperidol in serum. 4 In vitro experiments using sera from twenty-three healthy volunteers showed significant negative correlations (P less than 0.01) between age and percentage free haloperidol. 5 Thioridazine and oleic acid significantly enhanced the percentage of free haloperidol in normal human sera in vitro.

Adult↗
PubMed1991

Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase).

1. The conversion of haloperidol (HAL) to reduced haloperidol (RHAL) and then back to HAL has been established in vivo and observed in psychiatric patients. The reduction of HAL to RHAL is known to be catalysed by a ketone reductase, while the nature of oxidation back to HAL is the subject of the present study. 2. We examined the in vitro oxidation of RHAL to HAL in human livers. The activity was microsomal and evidence is presented to suggest that the sparteine/debrisoquine metabolizing isoenzyme P450IID6 contributes to this oxidation. 3. Reciprocal inhibition studies between RHAL and sparteine, a specific substrate for cytochrome P450IID6, indicated that both compounds compete for the same binding site. Quinidine, the most specific inhibitor for this cytochrome P450 potently inhibited the oxidative conversion of reduced haloperidol to haloperidol. A significant correlation (rs = 0.62, P less than 0.01) was found between RHAL oxidation and sparteine oxidation in a study involving 17 human liver samples.

Cytochrome P-450 CYP2D6↗
PubMed1982

Toxic haloperidol reactions with observation of serum haloperidol concentration in two children.

In 2 children who accidentally received haloperidol (0.26 mg/kg in one and 0.10 mg/kg in another) from a prescription error, haloperidol concentrations in serum in both cases and in cerebrospinal fluid in one case were measured with the radioimmunoassay method during the development of the toxic drug reactions. The serum haloperidol concentrations in both cases were far beyond the proposed therapeutic range in children. Our cases are generally compatible with previous findings of others and indicate that the intensity and/or incidence of toxic reactions of haloperidol may be related to plasma concentrations.

Basal Ganglia Diseases↗
PubMed1990

Determination of haloperidol and hydroxy haloperidol in human plasma by high performance liquid chromatography.

A method has been developed for the separation and measurement of haloperidol and hydroxy haloperidol in human plasma through high performance liquid chromatography. The method uses chlorohaloperidol as an internal standard and provides a limit of detection of about 0.7 nmol/l for haloperidol and 0.67 nmol/l for hydroxy haloperidol. HPLC and RIA radioimmunoassay methods are compared.

Chromatography, High Pressure Liquid↗
PubMed1985

Failure of chronic haloperidol to affect prolactin secretion due to acute haloperidol administration.

Withdrawal from chronic haloperidol exposure was associated to unaltered circulating levels of prolactin (PRL), decreased 3H-spiperone binding sites in the anterior pituitary and increased 3H-spiperone binding sites in the striatum of male rats. Haloperidol (0.1 mg/kg ip) induced similar rises in plasma PRL in haloperidol-or saline-treated rats and the dose of 0.01 mg/kg was ineffective in both groups. These findings illustrate the poor relatedness existing at the pituitary D2 receptor between biochemical and functional indices.

Animals↗
PubMed1987

Recording oral activity in rats reveals a long-lasting subsensitivity to haloperidol as a function of duration of previous haloperidol treatment.

Rats pretreated with no drug or with one of two dose levels of continuous haloperidol for 6, 12, or 24 weeks were then given a 5 month drug free interval followed by a single injection of 1 mg/kg haloperidol. Oral movement activity was recorded 2 days before and 7 days after the acute injection of haloperidol using a computerized scoring apparatus. Whereas prior to the acute injection there were no differences between groups, postinjection scores indicated a linear response curve, with the animals which had the least time of exposure showing the greatest increases in oral movement behavior. These data indicate that duration of treatment is a more important factor than is dose level in the development of persistent changes in dopamine-mediated oral activity.

Animals↗
PubMed1993

Relation of plasma and red blood cells reduced haloperidol concentrations to haloperidol reductase activity assayed in red blood cells in psychiatric population.

1. Haloperidol (HAL) reductase activity in red blood cells (RBC) was determined by a newly developed assay method in 120 blood samples from 75 Japanese psychiatric patients receiving HAL. 2. Plasma concentrations of HAL and reduced haloperidol (RHAL), a reductive metabolite of haloperidol, were also measured in these samples. 3. RBC concentrations of HAL and RHAL were measured in 62 of these samples. 4. No significant correlations were found between HAL reductase activity in RBC vs plasma or RBC RHAL/HAL ratios, which may represent activity of the enzyme metabolizing HAL into RHAL. 5. RHAL concentrations were three times higher in RBC than in plasma, though HAL concentrations were at the same level in both tissues. This may reflect accumulation of RHAL in RBC.

Adolescent↗
PubMed1983

A behavior analysis of the offspring of "haloperidol-sensitive" and "haloperidol-resistant" gerbils.

The first generation (F1) offspring of haloperidol-sensitive (HS) and haloperidol-resistant (HR) gerbils were compared in a battery of motor ("catalepsy") tests, a novel cardboard-shredding (oro-facial stereotypy) test, and a holeboard (exploration) test. The F1 HS gerbils were more "cataleptic" than the F1 HR gerbils after haloperidol (1 and 3 mg/kg). The F1 HR gerbils showed more oro-facial stereotypy and more exploratory behavior than did F1 HS gerbils in undrugged tests. The F1 HS and F1 HR groups did not differ in "general activity" as measured by line crossings in an open field or by an electromagnetic monitor in the home cage. These results are preliminary behavioral evidence for a difference between HS and HR gerbils in dopaminergic or related functions.

Animals↗
PubMed1992

Haloperidol and reduced haloperidol serum levels: correlation with psychopathology in acute schizophrenia.

Serum levels of haloperidol (HPL) and reduced haloperidol (RHPL) as well as the RHPL/HPL ratio were determined in 55 acute schizophrenics on oral haloperidol medication and correlated over 28 days with psychopathology and extrapyramidal symptom scores. Linear and nonlinear models of serum concentration and psychopathology were tested at several time points. No single consistent model could be established for either HPL or RPHL. However, when non-parametrical methods are used HPL levels between 10 and 25 ng/ml can be shown to be significantly associated with better outcome during the first three weeks of treatment. RHPL is unsuitable for therapy monitoring, since equilibrium is not reached in the first four weeks of treatment. The RHPL/HPL ratio was found to rise continuously during the study, and it neither separated responders from nonresponders nor did it correlate with clinical outcome.

Adult↗
PubMedDate not supplied

Liquid chromatographic determination of reduced haloperidol and haloperidol concentrations in packed red blood cells from humans.

Haloperidol (H) is a neuroleptic drug that has one known biologically active metabolite, reduced haloperidol (RH). A liquid chromatographic method is described for the determination of both compounds in human red blood cell (RBC) samples. The drugs were extracted into hexane at high pH and back-extracted into 0.1M HCl. The acid solution was then analyzed by reversed-phase chromatography under the following conditions: column was ultrasphere ODS; eluant was acetonitrile:0.085M phosphate buffer (30:70), final pH was 3.5, flow rate was 2 mL/min; detection was by light absorption at 246 nm for H and 220 nm for RH. The minimum limits of quantitation for H and RH were 0.25 and 0.1 ng/mL of packed RBC respectively. For six selected patients on 10 or 20 mg per day of oral haloperidol the RBC to plasma concentration ratios for RH and H were 2.20 +/- 0.9 (SD) and 0.81 +/- 0.26, respectively. The data indicate that RH is more concentrated in RBC than in plasma.

Chromatography, High Pressure Liquid↗