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At least 199 records · Page 11Linked to original sources
PubMed1986

Serum concentrations and clinical effect of zuclopenthixol in acutely disturbed, psychotic patients treated with zuclopenthixol acetate in Viscoleo.

Zuclopenthixol acetate, 5%, in Viscoleo was administered IM to 19 acutely disturbed, psychotic patients in doses of 50-150 mg. Fifteen patients received one injection, whereas four of the patients had two or three injections, usually with intervals of 3 days. The zuclopenthixol concentrations in serum were measured in series of samples taken from each patient during a 3-day period following the injection. In patients given identical doses serum concentrations of about the same order were obtained. Significant and good correlations were found between dose and maximal serum concentration and between dose and area under the serum concentration curve. The average serum concentration curve obtained when adjusting the data to a 100 mg dose has a maximum of 41 ng/ml after about 36 h, decreasing to 15 ng/ml after 72 h. A dose of 50-150 mg zuclopenthixol acetate in Viscoleo appeared to be sufficient for controlling the symptoms for most acutely disturbed, psychotic patients. The frequency of side effects, including extrapyramidal reactions, was low and the adverse reactions mostly mild, indicating that the risks for severe complications generally might be minimal. With a rapid onset of action, few and mild side effects, good tolerability at the injection site, and a duration of effect of 2-3 days, zuclopenthixol acetate in Viscoleo appears to offer advantages compared to conventional neuroleptic treatment in patients in whom an acute, calming effect is desired.

Adult↗
PubMed1986

Zuclopenthixol levels in serum and breast milk.

Breast milk and serum samples were obtained from six psychotic patients 3 days-10 months after delivery. Five of the women were given zuclopenthixol PO daily, and one was given zuclopenthixol decanoate IM every 2 weeks. Zuclopenthixol was estimated in breast milk and serum by high performance liquid chromatography. The zuclopenthixol levels in milk were found to be 29% of the serum levels on average. Based on the drug levels found in milk, the daily dose to a suckling infant was estimated to be 0.5-5 micrograms zuclopenthixol, corresponding to a dose of 0.01-0.1 mg to an adult. It is not likely that such a low dose would cause any effects or side effects in the infant unless infants are very different from adults concerning metabolism or sensitivity to the drug. The suckling infants included in this study were apparently not influenced by the intake of zuclopenthixol with the milk.

Adult↗
PubMed1985

Zuclopenthixol decanoate in schizophrenia: serum levels and clinical state.

Serum concentrations of zuclopenthixol were determined in a group of 20 patients treated with a depot preparation, zuclopenthixol decanoate in Viscoleo. Clinical assessments according to a Clinical Global Impression (CGI) scale, Comprehensive Psychological Rating Scale (CPRS), 16-item subscale for schizophrenia, and the UKU side effect scale were performed on 3 consecutive days of injection. The serum concentrations showed a limited individual variation and a high and significant correlation between dose and serum concentration. One patient had a particularly high serum concentration of zuclopenthixol. This patient also had an elevated concentration of the N-dealkyl metabolite, but a low concentration of the sulphoxide. For serum concentrations versus clinical state and side effects some significant correlations were found. All correlations were positive, which means that the higher the serum concentration the poorer the clinical state of the patient. We think that this probably reflects a common clinical pattern of increasing the dose, when the antipsychotic response is unsatisfactory. The study also showed that for moderately ill patients, who were given the optimum dose of drug, the subgroup of patients not experiencing side effects had significantly lower serum concentrations than the subgroup with side effects.

Adult↗
PubMed1988

Milk concentrations of flupenthixol, nortriptyline and zuclopenthixol and between-breast differences in two patients.

Flupenthixol (FP), nortriptyline (NT) and zuclopenthixol, (ZCP) were determined in breast milk and plasma from 2 puerperal, lactating women with psychiatric disorders. The milk concentrations were equal to, higher and lower than those in plasma for FP, NT and ZCP, respectively. Variation in milk triglyceride concentration, but not milk pH, could partly explain between-breast differences in the milk concentrations. The study demonstrates the need for appropriate and representative milk sampling procedures. The estimated daily infant exposure averaged 0.5, 2.3 and 0.3% of the corresponding maternal weight related doses of FP, NT and ZCP. FP was also detectable in infant plasma. These drugs are not known to be harmful in small doses to breast-fed infants. However, concern about the effect of dopamine blocking agents on neurobehavioral mechanisms in animals warrants caution. If neuroleptics are required for a long period this risk must be weighed against the benefits of breast-feeding, also considering the psychological effects of the latter.

Adult↗
PubMed1992

Hypouricemic effect of zuclopenthixol: a potential marker of drug compliance?

Twelve newly-admitted psychotic patients were treated with clinical doses of zuclopenthixol (ZPT). Plasma uric acid (PUA) was measured before and during treatment. ZPT reduced PUA in all the patients by an average of 29.6% (P < 0.0001). PUA levels during treatment correlated with those obtained before treatment (R = 0.871, P < 0.0002). PUA returned to initial levels on discontinuation of treatment. Uric acid excretion increased during treatment. It is concluded that ZPT is a potent uricosuric agent, capable of producing persistent hypouricemia while administered. Such hypouricemia might be a useful indicator of drug compliance.

Adult↗
PubMedDate not supplied

Failure of pyridoxine to effect neuroleptic-induced hyperprolactinemia in psychotic patients.

The effects of acute and repeated administration of pyridoxine on serum prolactin levels were studied in 18 chronic schizophrenics, 10 women and 8 men, in whom hyperprolactinemia had been induced by long-term treatment with phenothiazines, haloperidol, sulpiride or clopentixol. The patients were divided into 5 groups: group 1 received 300 mg of the vitamin per os in a single dose; group 2 received 300 mg of the vitamin per os for 7 days; group 3 received 300 mg of the vitamin iv as a single bolus; group 4 received 600 mg of the vitamin iv as a single bolus; group 5 received 1200 mg of the vitamin per os in a single dose. Prolactin levels were examined before and 15, 30, 60, 90, 120 and 150 min after the single administration of pyridoxine, either iv or per os, and on days 3,5, 7 of the chronic administration. There was no decrease in prolactin levels either after oral or iv administration of the drug, given in single or repeated doses. Therefore, this treatment is not useful for the suppression of hyperprolactinemia induced by neuroleptics.

Adult↗
PubMed1999

Age at onset of schizophrenia and neuroleptic dosage.

BACKGROUND: Lower age at onset of schizophrenia has been traditionally associated with poorer response to treatment and less favourable prognosis. The aim of the study was to find out whether age at onset of schizophrenia is related to the dosage of typical neuroleptics in outpatients. METHOD: Age at onset was defined as age at first seeking of psychiatric help. Demographic, social and disease-related characteristics were studied in a group of 200 stable outpatients with schizophrenia (100 males and 100 females). Psychopathological symptoms were assessed with the Krawiecka Scale. Neuroleptic dosage was converted to milligrams of chlorpromazine equivalents and logarithmically transformed to obtain normal distribution. RESULTS: Onset of schizophrenia occurred earlier in males than in females. The average dosage was 251.7 (SD 303.9) mg chlorpromazine equivalents. In a multivariate linear regression model, lower age at onset and higher sum of symptoms were related to the drug dosage. CONCLUSION: The results confirm the findings of other authors that patients with lower age at onset are less responsive to typical neuroleptics. Some of the patients with early onset would be more appropriately treated with atypical neuroleptics, which may have better therapeutic efficacy.

Adult↗
PubMed2002

Maintenance therapy with zuclopenthixol decanoate: associations between plasma concentrations, neurological side effects and CYP2D6 genotype.

RATIONALE: Several antipsychotic drugs are metabolised by the polymorphic cytochrome P(450) CYP2D6. The impact of the polymorphism on the plasma levels and the occurrence of side effects have not been clearly established. OBJECTIVE: To investigate the impact of the CYP2D6 polymorphism on the steady-state plasma concentrations of zuclopenthixol and the occurrence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) during treatment with zuclopenthixol-decanoate. METHODS: Fifty-two clinically stable schizophrenic outpatients on monotherapy with zuclopenthixol-decanoate (100-400 mg/4 weeks) were genotyped for the CYP2D6 variants CYP2D6*3 and CYP2D6*4. Steady-state plasma levels of zuclopenthixol were analysed using high-performance liquid chromatography. Assessments of EPS, TD and psychopathology were performed twice with an 8-week interval using the extrapyramidal symptoms rating scale, the abnormal involuntary movement scale and the brief psychiatric rating scale. RESULTS: Thirty-five patients were homozygous extensive metabolisers (EMs), 13 were heterozygous EMs and 4 were poor metabolisers (PMs). While there were no significant genotype-related differences in the doses of zuclopenthixol decanoate, PMs as well as heterozygous EMs had significantly higher steady-state plasma levels of zuclopenthixol than homozygous EMs (median 9.5 nmol/l; 8.2 nmol/l and 5.9 nmol/l, respectively, P<0.05). The median dose-corrected plasma concentrations were 0.029, 0.038 and 0.048 nmol.l(-1).mg(-1) in homozygous EMs, heterozygous EMs and PMs, respectively, with statistically significant differences between homozygous EMs and heterozygous EMs ( P=0.014) and homozygous EMs and PMs ( P=0.03). Patients with neurological side effects were significantly older than patients without ( P=0.02 in case of parkinsonism and P=0.04 in case of TD). Mutant CYP2D6*3 and *4 alleles tended to occur more frequently in patients with neurological side effects. An odds ratio (OR) of 2.3 (95% confidence interval 0.7-6.9) for development of parkinsonism and an OR of 1.7 (95% confidence interval 0.5-4.9) for TD was calculated in an individual with at least one mutated allele. However, the ORs were not statistically significant. CONCLUSIONS: The higher zuclopenthixol steady-state plasma concentrations in heterozygous EM and PM schizophrenic patients receiving monotherapy with zuclopenthixol-decanoate than in homozygous EMs indicates a significant role of CYP2D6 in the systemic elimination of zuclopenthixol. The tendencies for patients carrying at least one mutated CYP2D6 gene to have an increased risk of parkinsonism and TD are in accordance with previous studies. Age was a significant risk factor for neurological side effects.

Adult↗
PubMed1990

Intermittent versus continuous neuroleptic treatment in a rat model.

The treatment schedule for neuroleptic therapy is of relevance when evaluating the development of side-effects. Seventy-five rats were treated discontinuously or continuously with the predominantly dopamine D2 receptor blocker haloperidol or the combined dopamine D1/D2 receptor blocker zuclopenthixol for 15 weeks. During and after treatment, a broad spectrum of behavioural parameters including vacuous chewing movements and tongue protrusions were observed. Discontinuous neuroleptic treatment as opposed to continuous neuroleptic treatment produced a significant long-lasting increase in oral activity. The changes were most pronounced in haloperidol-treated rats. The differences observed may have methodological implications for animal models of neuroleptic-induced movement disorders. Our findings are consistent with the hypothesis that pharmacological sensitization to the dyskinetic side-effects of neuroleptics develops when the drug effect is allowed to wear off between repeated administrations.

Animals↗
PubMed1990

Effect of a dopamine D-1 agonist in rats treated chronically with zuclopenthixol.

We have previously demonstrated long-lasting increases in vacuous chewing movements (VCM) and tongue protrusions in rats treated discontinuously (DISC), but not continuously (CONT), with neuroleptics. To test whether this increase in mouth movements could be a result of exaggerated activity at the D-1 site, 34 rats were divided into three groups receiving the neuroleptic zuclopenthixol (ZU) DISC or CONT for 15 weeks, or no treatment. After withdrawal DISC treated animals showed an increase in oral activity compared to CONT treated. Two weeks after termination of medication the animals were tested with the D-1 agonist SK&F 38393. The increases in VCM after SK&F 38393 did not differ among the groups, but in contrast to control (CTRL) rats, treated rats showed a significant increase in tongue protrusions. There were no significant differences in the densities of D-1 and D-2 receptors in the striatum between the groups. The increase in tongue protrusions after SK&F 38393 in neuroleptic treated animals implies behavioural D-1 receptor supersensitivity. No significant differences in the rise in tongue protrusions and VCM after SK&F 38393 were seen between DISC and CONT treated animals. Our results thus do not indicate that increased D-1 receptor responsiveness is significant for the rise in spontaneous oral activity found after neuroleptic withdrawal.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Antistereotype effects of ceruletide and some neuroleptics differentiated by interactions with clonazepam, muscimol, scopolamine and clonidine.

Compulsive gnawing was produced in mice by administration of either methylphenidate or (after sensitizing pretreatment with the neuroleptic, tetflutixol) apomorphine. Drugs which antagonise stereotypy, such as ceruletide (CER, a sulphated decapeptide related to cholecystokinin octapeptide), haloperidol, zuclopenthixol and fluphenazine were applied in equipotent doses (reducing stereotypy by 80%). Clonazepam, muscimol, clonidine and scopolamine (but not methylscopolamine) antagonized to a different extent the antistereotype effect of ceruletide and the neuroleptics. The ED50s for clonazepam and other drugs, were determined; clonazepam had the greatest potency. Regarding the antagonism of the antistereotype effect, ceruletide was similar to but by no means congruent with haloperidol. The antagonism of the antistereotype effect was specific because other effects of ceruletide and cholecystokinin octapeptide (inhibition of exploratory rearing activity, ptosis, antinociception, hypothermia) were not antagonized by clonazepam and only weakly modified by scopolamine. Methylscopolamine was ineffective throughout, indicating a central site for the mechanism of the actions studied of scopolamine. In conclusion, the antistereotype effect of ceruletide is different from that of conventional neuroleptic drugs and functionally independent of other behavioural effects of the cholecystokinin-like peptides.

Animals↗
PubMed1990

Dynorphin A and substance P in the cerebrospinal fluid of schizophrenic patients.

Radioimmunoassay procedures were used to assay levels of dynorphin A (DYN A) and substance P-like activity (SP) in cerebrospinal fluid (CSF) obtained from 10 schizophrenic patients before and after neuroleptic treatment, from 10 matched patients with other psychiatric disorders before and after treatment, and from 10 nonpsychiatric surgical controls. The highest mean concentration of CSF DYN A was found in the schizophrenic group on admission (significant vs. nonpsychiatric controls). The concentration remained almost unaltered after 4 weeks of zuclopenthixol treatment despite a highly significant decrease of overt psychopathology assessed by the Brief Psychiatric Rating Scale (BPRS). There was no significant difference between the mean CSF DYN A levels of the nonschizophrenic psychiatric patients and the surgical controls. When all psychiatric patients were pooled together, there was a significant correlation between the level of CSF DYN A and the BPRS total score. With regard to CSF SP levels, no statistically significant differences were observed within or between the groups studied. Neither was there a significant correlation between the concentration of CSF SP and overt psychopathology. Nevertheless, the mean CSF SP concentration of three patients with major depression was clearly higher than the corresponding mean concentration of the other patients in the nonschizophrenic group.

Adult↗
PubMed1989

Pharmacokinetics of three different injectable zuclopenthixol preparations.

1. The zuclopenthixol concentrations in serum has been investigated in man and dog after injection of three different zuclopenthixol preparations. These were zuclopenthixol dihydrochloride in aqueous solution, zuclopenthixol acetate in oil and zuclopenthixol decanoate in oil. 2. The pharmacokinetic profiles of the three injectable zuclopenthixol preparations are very different. Maximum serum levels are obtained after about 1 hour for zuclopenthixol dihydrochloride, after 36 hours for zuclopenthixol acetate and after one week for zuclopenthixol decanoate. 3. The different pharmacokinetics of the three injectable zuclopenthixol preparations are reflected in their clinical properties.

Adult↗