Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Flupenthixol”

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 37 records · Page 2Linked to original sources
PubMed1977

Radioimmunoassay for flupenthixol in plasma.

We describe a radioimmunoassay for the neuroleptic drug flupenthixol, suitable for routine monitoring of its concentration in blood. Antibodies for the assay were raised in a sheep against a 7-carboxyflupenthixol/ovalbumin conjugate. The resulting assay, with [3H] flupenthixol as the label, is capable of detecting 2.0 microgram of flupenthixol per liter, in a 100-microliter plasma sample. The antiserum shows no cross reactivity with tricyclic drugs and low interference from the major metabolites of flupenthixol. Concentrations in plasma after a single oral dose of flupenthixol have been followed in one volunteer. Peak values were reached after 3 h. Determinations of flupenthixol after fortnightly intramuscular depot injections of the sustained-release preparation, flupenthixol decanoate, showed the extent of fluctuations during this period.

Cross Reactions↗
PubMed1982

Induction of microsomal enzyme activity by flupenthixol in chronic schizophrenics.

The effect of long-term treatment with flupenthixol on hepatic microsomal enzyme activity was studied in 12 chronic schizophrenic outpatients who had been receiving two weekly maintenance doses for at least 6 months. Antipyrine half-life was measured in the 12 patients while they continued to receive the drug. Flupenthixol was then discontinued for 6 weeks and antipyrine half-life was repeated in 7 of the 12 patients. In the 12 patients the plasma antipyrine elimination half-life was 4-24 h (mean 9.73 +/- 1.61 h) when receiving flupenthixol and there was a significant negative correlation between antipyrine half-life and the dose of flupenthixol (r = 0.582, P less than 0.05). In the seven patients to whom antipyrine was given on two occasions, antipyrine half-life was 7.33 +/- 1.07 h and 12.04 +/- 1.87 h on and off flupenthixol treatment respectively. The clearance significantly decreased when flupenthixol was discontinued, but there was no change in the apparent volume of distribution.

Adult↗
PubMed1994

Effects of the neuroleptic alpha-flupenthixol on latent inhibition in aversively- and appetitively-motivated paradigms: evidence for dopamine-reinforcer interactions.

Three experiments examined the influence of the dopamine (DA) D1/D2 receptor antagonist alpha-flupenthixol on the latent inhibition (LI) effect. LI is a phenomenon which is manifest when non-reinforced pre-exposure to a stimulus retards subsequent conditioning to that stimulus, and has been proposed as an animal model of the selective attentional processes that are disrupted in acute schizophrenia. Experiment 1 extended previous findings that neuroleptics enhance the LI effect in conditioned suppression paradigms in rats to alpha-flupenthixol (0.23 mg/kg). Experiment 2 demonstrated that this enhancement of the LI effect was also seen in a parallel appetitively-motivated conditioning paradigm at the same dose. In both Experiment 1 and Experiment 2, the enhancement of the LI effect by alpha-flupenthixol appeared to be accompanied by a decrease in the impact of the reinforcer (be it appetitive or aversive). Experiment 3 investigated the possible role of the reinforcer in the effect of alpha-flupenthixol on the LI effect in the aversive, conditioned suppression paradigm by increasing the intensity of footshock in rats treated with alpha-flupenthixol. Increasing the intensity of the footshock completely abolished the enhancement of LI found following injection of alpha-flupenthixol, a result which could not be attributed to a floor effect. The results provide no support for interpretations of the influence of DA manipulations on the LI effect that draw parallels with deficits in selective attention observed in acute schizophrenia.

Acoustic Stimulation↗
PubMed2006

Post-training intra-striatal scopolamine or flupenthixol impairs radial maze learning in rats.

Systemic treatments with acetylcholine (ACh) or dopamine (DA) receptor antagonists during hours 0-4 but not during hours 5-8 following training on a radial arm maze (RAM) or lesions of the dorsal striata impair learning. This suggested that intra-striatal infusions of ACh or DA receptor antagonists during hours 0-4 following training may impair learning. Rats were randomly assigned to groups (ns=5-11) receiving dorsal striatal infusions of the ACh receptor antagonist scopolamine (0-18 microg/microL at 0 and 2h or at 4 and 6h after training), the DA receptor antagonist cis-flupenthixol (0-25 microg/microL at 0, 4 or 12h after training) or the inactive isomer trans-flupenthixol (6 microg/microL at 0 h after training). Scopolamine and cis-flupenthixol impaired the habit-learning version of the task. Given after hours 0-4 following training, the effects of scopolamine were diminished but those of cis-flupenthixol were not. Trans-flupenthixol produced less impairment than cis-flupenthixol. Results suggest that ACh and DA receptors in the dorsal striatum during hours 0-4 following training play a role in habit learning.

Acetylcholine↗
PubMed1983

Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology.

Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate).

Adult↗
PubMed2003

Flupenthixol versus risperidone: subjective quality of life as an important factor for compliance in chronic schizophrenic patients.

OBJECTIVE: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end "haloperidol" to its atypical end "clozapine", flupenthixol has typical and atypical characteristics. METHODS: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30). RESULTS: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories "control of their thoughts", concentration and "feeling better in general" ameliorated in both groups. In the flupenthixol group, the "ability to cope with stress", "feel more relaxed" and the "ability to achieve something" improved significantly more than in the risperidone group. CONCLUSIONS: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups.

Adolescent↗
PubMed1989

An open clinical trial with the long-acting neuroleptics flupenthixol decanoate and fluphenazine decanoate in the maintenance treatment of schizophrenia.

An open clinical trial was carried out in 21 chronic schizophrenics to assess the effectiveness and side-effects of treatment with depot neuroleptics. All patients had been stabilized on fluphenazine decanoate for at least 6 months and on entry to the study were given the choice of continuing with this treatment or changing over to flupenthixol decanoate. Sixteen patients chose to receive flupenthixol decanoate (40 mg) and the other 5 fluphenazine decanoate (25 mg). Doses were given every 4 weeks during the 12-week study period. Clinical assessments were carried out every 4 weeks (Weeks 0, 4, 8 and 12) using the Brief Psychiatric Rating Scale and a side-effects checklist, and the Hamilton Rating Scale for Depression, the Schedule for Affected Disorders and Schizophrenia--Change Version, and the Global Assessment Scale were completed on entry (Week 0) and at the end of the study (Week 12). The results indicated that symptoms of depression, withdrawal, worrying, and psychomotor retardation were improved significantly (p less than 0.05) more with flupenthixol than with fluphenazine. The frequency of side-effects decreased during treatment with flupenthixol and there was a tendency towards fewer side-effects in the flupenthixol group than in the fluphenazine group after 8 weeks of treatment. It is concluded that a group of schizophrenic patients characterized by depressive symptoms or side-effects attributable to a prescribed neuroleptic might benefit from a switch to flupenthixol treatment.

Clinical Trials as Topic↗
PubMed1985

Psychosomatic disorders in general practice: comparisons of treatment with flupenthixol, diazepam and sulpiride.

One hundred and thirteen patients diagnosed as suffering from one of four common psychosomatic syndromes (psychogenic headache, cardiac neurosis, functional disturbance of the colon, or pruritus) were treated by two groups of general practitioners with flupenthixol or diazepam or sulpiride. Flupenthixol was compared with diazepam in 58 patients in one group of Belgian practices, and with sulpiride in 55 patients in another group of practices and assessed over a 4-week period for therapeutic response and adverse effects. Flupenthixol was given in a dosage of 0.5 to 2 mg a day, diazepam in a dosage of 2.5 to 10 mg a day and sulpiride 100 to 200 mg a day, in identical capsules. In the flupenthixol/diazepam comparison, there were 7 drop-outs (3 flupenthixol, 4 diazepam). Marked or moderate reduction in global assessment of illness occurred in both treatment groups, but there was no significant difference in the therapeutic effect of the two drugs. The incidence of side-effects was low and similar in the two groups. In the flupenthixol/sulpiride comparison, there were 10 drop-outs (7 flupenthixol, 3 sulpiride). A significant reduction in symptoms occurred in both treatment groups, but this was more rapid in the flupenthixol group. Side-effects were infrequent and mild in both groups.

Adult↗
PubMed1985

Assay of dopamine receptors with [alpha-3H]flupenthixol.

Two major classes of dopamine receptors, called D-1 receptors and D-2 receptors, have been identified. [alpha-3H]Flupenthixol has been used as a radioligand for the study of D-1 receptors, which are thought to act through stimulation of adenylate cyclase activity. Previous studies in our laboratory have shown that the D-2 receptors in rat caudate labeled by [3H]spiroperidol also have a high affinity for alpha-flupenthixol. The present experiments show that although Scatchard analysis of the binding of [alpha-3H]flupenthixol is consistent with the presence of a homogeneous population of receptors, subpopulations of these sites can be distinguished by their differing affinities for spiroperidol, which has a Kd for D-1 receptors of about 0.3 microM and a Kd for D-2 receptors of approximately 50 pM. The number of D-1 receptors in rat striatum is approximately 4 times the number of D-2 receptors. D-1 receptors can be studied by including 10 nM spiroperidol in assays carried out with [alpha-3H]flupenthixol, thus blocking the binding of [alpha-3H]flupenthixol to D-2 receptors. The affinity of these receptors for dopamine is decreased by GTP, as has been observed in studies of other receptors whose effects are mediated through changes in adenylate cyclase activity. In the presence of spiroperidol, the Hill coefficients determined from dose-response curves of the inhibition of the binding of [alpha-3H]flupenthixol by antagonists or by agonists in the presence of GTP suggest that the binding reaction obeys simple Michaelis-Menten kinetics for a single class of binding sites.

Animals↗
PubMed1983

Flupenthixol versus haloperidol in acute psychosis.

Forty acutely psychotic patients were treated either with flupenthixol drops or haloperidol drops in an open, 28-day controlled study. The flupenthixol group comprised 11 schizophrenic, 8 manic, and 1 paranoid patient and there were 10 schizophrenic, 5 manic, and 5 paranoid patients in the haloperidol group. Mean daily dosage was approximately 112 mg flupenthixol and 18 mg haloperidol. Clinically, both drugs showed an antipsychotic effect. In the schizophrenic patients there was a definite trend towards a more rapid relief of the psychotic symptoms after flupenthixol treatment. In contrast to haloperidol, flupenthixol showed a mood elevating effect and an effect on the negative symptoms, e.g. emotional withdrawal, motor retardation, blunted affect, and disorientation. With both drugs, the most troublesome side-effects were extrapyramidal in nature. Initially, they were more common in the flupenthixol group: later the incidence was similar.

Acute Disease↗
PubMed1998

Expression of testosterone conditioned place preference is blocked by peripheral or intra-accumbens injection of alpha-flupenthixol.

Previous evidence indicates that peripheral and intranucleus accumbens injections of testosterone have rewarding effects in male rats as measured in a conditioned place preference (CPP) paradigm. The present study investigated the neurochemical bases of the rewarding properties of testosterone by examining the effect of peripheral and intranucleus accumbens injection of the dopamine receptor antagonist alpha-flupenthixol on expression of testosterone-induced CPP. On alternating days, adult male Long-Evans rats received peripheral injections of testosterone in a water-soluble hydroxypropyl-beta-cyclodextrin (HBC) inclusion complex (0.8 mg/kg) or saline-HBC immediately prior to being confined for 30 min to one of two compartments of a place preference apparatus. All rats received 8 days of pairings (four hormone pairings, four saline pairings). On day 9 the rats were given a 20-min test session during which they had access to all compartments of the apparatus. No hormone was injected prior to the test session; however, rats received a peripheral (20 min prior; 0.2, 0.3 mg/kg) or intra-accumbens (2 min prior, 5.0 micrograms) injection of alpha-flupenthixol or saline. On the test day, rats receiving saline injections spent significantly more time in the compartment previously paired with injections of testosterone than in the compartment previously paired with vehicle injections. In contrast, rats receiving peripheral or intra-accumbens alpha-flupenthixol injections did not spend significantly more time in the compartment previously paired with testosterone. The blockade of testosterone CPP was not due to an effect of alpha-flupenthixol on motor behavior. The findings provide further evidence of the rewarding affective properties of testosterone and indicate that peripheral administration and intra-accumbens administration of alpha-flupenthixol block expression of testosterone CPP. The rewarding affective properties of testosterone are mediated, at least in part, via an interaction with the mesolimbic dopamine system.

Animals↗
PubMed1997

Symmetrical effects of amphetamine and alpha-flupenthixol on conditioned punishment and conditioned reinforcement: contrasts with midazolam.

In a test of conditioned punishment, saline-treated controls showed a moderate bias in responding away from a lever producing a response-contingent auditory conditioned stimulus (CS) that had been paired with mild footshock during training and towards a lever producing a neutral auditory CS. Systemic treatment with the indirect dopamine (DA) agonist amphetamine (0.25-1.0 mg/kg) produced a dose-dependent increase in the punishing effect of the aversive CS, whilst responding on the neutral CS lever was unchanged. Treatment with the dopamine-receptor antagonist alpha-flupenthixol (0.125, 0.25 mg/kg) decreased the efficacy of the punishing CS, but again left responding on the neutral lever unchanged. The benzodiazepine midazolam (0.1, 0.3 mg/kg) had a similar effect to alpha-flupenthixol, but treated animals showed a preference for the aversive CS. Parallel results were observed with amphetamine (0.25 mg/kg) and alpha-flupenthixol (0.125, 0.25 mg/kg) in a matched test of positive conditioned reinforcement, with amphetamine enhancing, and alpha-flupenthixol reducing, the efficacy of the CS paired with food. Midazolam treatment (0.1-1.0 mg/kg) had no effect on the reinforcing impact of an appetitive CS. Thus dopaminergic agents modulate the behavioural impact of both appetitively and aversively motivated conditioned stimuli on instrumental performance, whilst the benzodiazepine midazolam has a selective impact on aversively-motivated stimuli that is qualitatively distinct from that of the dopaminergic antagonist alpha-flupenthixol.

Amphetamine↗
PubMed1988

Microinjection of cis-flupenthixol, a dopamine antagonist, into the medial preoptic area impairs sexual behavior of male rats.

Systemically administered dopamine agonists have been shown to facilitate copulation in male rats. Microinjection of the dopamine agonist apomorphine into the medial preoptic area has also been reported to facilitate sexual behavior. The present experiments investigated the effects of medial preoptic microinjections of the dopamine antagonist cis-flupenthixol on male rat copulatory behavior. Fewer males initiated copulation and fewer ejaculated following flupenthixol administration. Those males that did ejaculate following flupenthixol injections had fewer ejaculations and longer interintromission intervals. Flupenthixol also antagonized the facilitative effects of apomorphine injections into the medial preoptic area. Flupenthixol and apomorphine produced only minor alterations in noncopulatory behaviors. The results suggest that dopamine receptors within the medial preoptic area are important in the regulation of masculine sexual behavior in the rat.

Animals↗
PubMed1991

Microinjection of the dopamine antagonist cis-flupenthixol into the MPOA impairs copulation, penile reflexes and sexual motivation in male rats.

Microinjection of the dopamine antagonist cis-flupenthixol into the medial preoptic area was previously shown to impair male rat copulatory behavior. The present experiments provide further evidence of cis-flupenthixol's inhibitory effects on male sexual behavior. Following microinjections of moderate to high doses of cis-flupenthixol, males exhibited slower copulatory rates and fewer ejaculations in copula, fewer ex copula erections and penile movements, and reduced sexual motivation in an X-maze. Locomotion in the X-maze was not significantly affected. Microinjections of the inactive isomer trans-flupenthixol produced no change in any behavioral measure, indicating that cis-flupenthixol's effects were receptor mediated. We suggest that dopamine receptors in the MPOA influence copulation primarily by regulating reflexive and motivational factors, but not locomotion.

Animals↗
PubMed1983

Characteristics of 3H-cis-flupenthixol binding in rat striatum.

Characteristics of membrane receptor binding by 3H-cis-flupenthixol were examined in rat striatum. Using modifications of standard dopamine receptor binding techniques, it was possible to obtain 70% specific binding with 3H-cis-flupenthixol. Association and dissociation rates were very rapid, with equilibrium reached in 2 min and half-time of dissociation being 1 min. Analysis of saturation and competition studies using cis-flupenthixol and spiroperidol indicated that cis-flupenthixol binds to two striatal receptors with apparent KD's of 0.7 and 4.8 nM. It is suggested these represent D1 and D2 dopamine receptors respectively. The further characterization of the properties of cis-flupenthixol binding presented here should enable more detailed studies of multiple dopamine receptors to be designed.

Animals↗
PubMed1980

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. III. Serum levels.

Serum concentrations of clopenthixol and flupenthixol have been determined during a four weeks dosage interval in patients treated with intramuscular injections of clopenthixol decanoate or flupenthixol palmitate in Viscoleo. Maximal drug levels were attained by the end of the first week after injection of either preparation. A period of exponential decline was then recorded. The half-lives were estimated to 19 days for clopenthixol and 17 days for flupenthixol. These half-lives most likely refer to the rate of release from the oil depot and not to elimination of drug. The mean ratio between maximal and minimal drug levels was 2.5 for clopenthixol and 3.7 for flupenthixol. Systemic clearance was estimated to about 0.7 l/min and 0.5 l/min, respectively. Significant correlation was found between the administered doses and recorded serum levels, between doses and estimated areas under the serum concentration curves, and also between areas and drug levels. The data indicate more limited individual variability than that seen with other psychotropic drugs, given orally. The study clearly demonstrates, that significant serum levels of active drug is maintained throughout the dosage interval by intramuscular injection of clopenthixol decanoate or flupenthixol palmitate in Viscoleo every fourth week.

Ambulatory Care↗
PubMed1976

A controlled comparison of flupenthixol and amitriptyline in depressed outpatients.

Sixty depressed outpatients were allocated to treatment with either amitriptyline (75-225 mg/day) or flupenthixol (1-5-4-5 mg/day) in flexible dosage for six weeks under double-blind procedures. Various objective and subjective assessments were carried out before and after one, three, and six weeks of treatment. Twenty-three patients completed the course of amitriptyline and 28 the course of flupenthixol. Almost all variables improved significantly over time, irrespective of drug. On most ratings there were no significant differences between the two drugs, but the trends favoured flupenthixol. In particular, flupenthixol lessened anxiety scores more than amitriptyline. Unwanted effects were few and not troublesome except in two patients receiving amitriptyline. Flupenthixol, in low dosage, is a useful alternative antidepressant for depressed outpatients.

Adult↗
PubMed2003

Flupenthixol in relapse prevention in schizophrenics with comorbid alcoholism: results from an open clinical study.

Substance use, especially alcoholism, has been recognized as a significant problem in schizophrenic patients, though only a few studies on the effects of pharmacotherapy in these patients have been conducted so far. The thioxanthene neuroleptic flupenthixol, which can be given intramuscularly (i.m.) for improving compliance, has been studied as a possible anti-craving drug both in animal models of alcoholism and some clinical studies. Pilot studies suggest that comorbid schizophrenics with substance use may benefit from treatment with flupenthixol. Efficacy of flupenthixol (10-60 mg i.m.) in reducing alcohol consumption of dual diagnosis patients was studied in an open 6-month clinical trial in 27 schizophrenics with comorbid alcoholism. Twenty-one patients entered the intention-to-treat analysis. Fourteen subjects were completers, 13 dropped out. Six patients completely abstained from alcohol during treatment. Alcohol consumption was significantly reduced compared to baseline (4 weeks before treatment as measured by timeline follow-back interview). In general, while patients showed a marked improvement concerning alcohol consumption, only a slight improvement in psychopathology was recorded. Overall tolerability was good. These data indicate a probable beneficial effect of flupenthixol in schizophrenic patients with comorbid alcoholism. Although the efficacy of flupenthixol as an anti-craving drug in dual diagnosis patients has to be explored in further studies, the drug may be considered a promising medication for these patients.

Adult↗