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PubMed1984

Flupenthixol versus diazepam in the treatment of psychosomatic disorders: a double-blind, multi-centre trial in general practice.

In a Finnish general practice 120 patients with psychosomatic disorders, manifest as syndromes of tension headache, cardiac neurosis, dizziness or muscular tension, were randomly allocated to treatment over a 4-week period with either flupenthixol (1 to 2 mg per day) or diazepam (5 to 10 mg mg per day). The 4 syndromes and 12 associated symptoms (anxiety, fatigue, depression, pain, asthenia, muscle fatiguability, tension, dyspnoea, restlessness, palpitations, sleep disorders, and vertigo) were rated on a 4-point scale on entry, at 2 weeks and at 4 weeks. Both drugs reduced significantly the average total scores for syndromes and single symptoms after 2-weeks' treatment. Flupenthixol was the more effective in relieving fatigue and vertigo; diazepam in relieving headache, anxiety, tension, restlessness and sleep disturbance. Cardiac neurosis, palpitations and general muscular tension responded poorly to both drugs. After 4 weeks, relief of vertigo, pain and fatigue was more evident in the flupenthixol group, and of anxiety, tension and restlessness in the diazepam group. Side-effects were complained of at some stage by 17 patients in the flupenthixol group (9 of fatigue, 5 of sleep disturbance, 1 of constipation, 1 of extrapyramidal symptoms, and 1 of weight gain) and by 16 patients in the diazepam group (10 of fatigue, 4 of sleep problems and 2 of diarrhoea).

Adult↗
PubMed1979

Blood levels of flupenthixol in patients with acute and chronic schizophrenia.

Plasma levels of flupenthixol were estimated by three methods in 30 patients with acute schizophrenia and 29 patients with chronic schizophrenia. These levels were related to clinical response, anterior pituitary hormone secretion, platelet monoamine oxidase activity, the effects of the concurrent administration of anticholinergic drugs, and body weight. No clearcut relationships between plasma flupenthixol levels and any of these variables were demonstrated. The practical clinical value of the estimation of plasma flupenthixol is limited at the present time.

Acute Disease↗
PubMed1979

3-Methoxy-4-hydroxyphenylglycol excretion in acutely schizophrenic patients during a controlled clinical trial of the isomers of flupenthixol.

Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo. Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables. In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial. However in females no relationship between MHPG excretion and outcome was established. During the trial there was a reduction in MHPG excretion in patients treated with beta-flupenthixol but no decrease in the group treated with alpha-flupenthixol or chlorpromazine. In patients on placebo there was a reduction in MHPG excretion in those who did well clinically, but not in those who did poorly. Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia, but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration.

Adult↗
PubMed1985

Effects of discontinuous drug administration on the development of dopamine receptor supersensitivity during chronic trifluoperazine or cis-flupenthixol administration to rats.

Rats received continuous or discontinuous administration of trifluoperazine or cis-flupenthixol in drinking water for up to 12 months. Continuous and discontinuous trifluoperazine administration had no consistent effect on apomorphine-induced stereotyped behaviour and there was no difference between drug treatments. Continuous and discontinuous cis-flupenthixol administration enhanced apomorphine-induced stereotypy, but there was no difference in the effect of the two drug treatments. Both continuous and discontinuous administration of trifluoperazine increased the number of specific striatal 3H-spiperone binding sites (Bmax). Over the period of treatment there was no difference in the effects of the different treatments. Continuous or discontinuous cis-flupenthixol intake did not increase Bmax after 6 or 12 months intake. Continuous or discontinuous neuroleptic treatment produced no difference in functional striatal dopamine receptor activity as judged by apomorphine-induced stereotyped behaviour. Ligand binding studies also suggest that the overall change in striatal receptor function is not affected by the use of a discontinuous drug regime.

Animals↗
PubMed1977

Effect of flupenthixol and butaclamol isomers on prolactin secretion in rats.

Cis (alpha)-flupenthixol and (+)-butaclamol are effective anti-psychotic agents but trans (beta)-flupenthixol and (-)-butaclamol are not. alpha-Flupenthixol was found to be 245 times more active in elevating rat plasma prolactin than the beta-isomer. The discrepancy between (+)-butaclamol and (-)-butaclamol was even greater. These results support the hypothesis that the dopamine receptors that mediate the effects of dopamine on prolactin secretion are similar to those that mediate the anti-psychotic effect of neuroleptic drugs.

Animals↗
PubMed1980

The locomotor effect of clonidine and its interaction with alpha-flupenthixol or haloperidol in the developing rat.

The interaction of clonidine with alpha-flupenthixol and haloperidol on the locomotion was investigation in the rat during postnatal development. A subcutaneous injection of clonidine 0.039--3.9 mu mol/kg produced a marked hypermotility in infant animals between day 1 and day 7 but hypomotility in animals older than 20 days. Pretreatment with alpha-flupenthixol and haloperidol significantly reduced clonidine-hypermotility in infants. In adult rats, clonidine-hypomotility were increased by a preceding administration of alpha-flupenthixol. It is suggested that intact function of both alpha-adrenoceptors and dopamine receptors is involved in the control of locomotor activity in developing rats and that there is the complex interaction of noradrenergic and dopaminergic system in the control of locomotor activity.

Age Factors↗
PubMed2000

The effects of d-amphetamine, chlordiazepoxide, alpha-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats.

RATIONALE: Inability to tolerate delays to reward is an important component of impulsive behaviour, and has been suggested to reflect dysfunction of dopamine systems. OBJECTIVES: The present experiments examined the effects of signalling a delayed, large reward on rats' ability to choose it over a small, immediate reward, and on the response to amphetamine, a dopamine receptor antagonist, and a benzodiazepine. METHODS: Three groups of Lister hooded rats were tested on a two-lever discrete-trial delayed reinforcement task in which they chose one pellet delivered immediately or four pellets delivered after a delay. This delay increased from 0 to 60 s during each session. Trials began with illumination of a houselight: in the Houselight group, this remained on during the delay and feeding period. In the No Cue group, the houselight was extinguished at the moment of choice. In the Cue group, a stimulus light was illuminated during the delay. Once trained, the rats were challenged with d-amphetamine (0.3, 1.0, 1.6 mg/kg), chlordiazepoxide (1.0, 3.2, 5.6, 10 mg/kg), alpha-flupenthixol (0.125, 0.25, 0.5 mg/kg), and various behavioural manipulations. RESULTS: Subjects' choice became and remained sensitive to the delay; the cue speeded learning. Amphetamine decreased choice of the large reinforcer in the No Cue group and increased it in the Cue group. alpha-Flupenthixol and chlordiazepoxide generally decreased preference for the delayed reinforcer; flupenthixol reduced the cue's effects, but chlordiazepoxide did not interact with the cue condition. CONCLUSIONS: Signals present during a delay can enhance the ability of amphetamine to promote choice of delayed rewards.

Animals↗
PubMed1997

Differential effects of ondansetron and alpha-flupenthixol on responding for conditioned reward.

Previous experiments have suggested that 5-HT3 antagonists such as ondansetron may alter reward-related behaviour that is dependent in part upon raised mesolimbic dopamine activity. However, the evidence for this is far from conclusive. One major behavioural role of dopamine is in the control of behaviour elicited by conditioned rewarding stimuli. To date, the effects of 5-HT3 antagonists on this function of mesolimbic dopamine have not been examined. Two experimental procedures were employed to examine the effects of ondansetron (10 and 100 micrograms/kg) on the acquisition of responding for conditioned reward, and on the response potentiating effect of intra-accumbens d-amphetamine (10 micrograms). These effects were compared to those elicited by the dopamine antagonist alpha-flupenthixol (0.1 mg/kg). In the first procedure, rats were trained to associate food pellet delivery with a conditioned stimulus (CS). Rats subsequently allowed to respond on a lever delivering this CS, and on an inactive lever, showed a greater preference for the lever delivering the CS, indicating that this CS functioned as a conditioned reward (CR). Ondansetron administered during the conditioning phase did not alter subsequent responding for the CR, but alpha-flupenthixol induced a small but significant reduction in responding on the CR lever. These results suggest that blockade of dopamine receptors, but not 5-HT3 receptors interfere with the learning of stimulus reward relationships. In the second procedure, d-amphetamine injected into the nucleus accumbens markedly potentiated responding for CR. Ondansetron at 10 micrograms/kg induced a small attenuation of this effect, without altering responding in its own right. However, at a higher dose (100 micrograms/kg) ondansetron plus amphetamine treatment significantly enhanced responding on the inactive lever. At both doses, the net effect of ondansetron was to produce a subtle impairment in the allocation of responses such that the differential responding on the CR versus NCR lever was diminished. In contrast to these effects alpha-flupenthixol significantly attenuated d-amphetamine's selective enhancement of responding for conditioned reward, as well as impairing the ability of the conditioned reward to elicit and maintain behaviour. These results confirm the role of dopamine in responding for conditioned reward, and suggest a possible modulators role for 5-HT3 receptors in this process. However, the effects of ondansetron on the acquisition of, and responding for, conditioned reward are clearly different from those induced by blockade of dopamine receptors.

Animals↗
PubMed1976

Alpha-flupenthixol-induced hyperactivity by chronic dosing in rats.

Socially reared and isolation-reared rats treated chronically since weaning with alpha-flupenthixol showed elevated levels of spontaneous locomotor activity compared with control treated rats. However, chronic apomorphine treatment had no effect on spontaneous locomotor activity. Chronic alpha-flupenthixol treatment enhanced stereotyped behaviour after 1.5 mg/kg d-amphetamine or 0.5 mg/kg apomorphine in the socially reared condition. 'Spontaneous stereotypies' were also observed in the chronic alpha-flupenthixol-treated animals. Chronic apomorphine treatment did not affect stereotyped responding. The results are discussed in terms of 'behavioural supersensitivity'.

Animals↗
PubMed1994

A single injection of either flupenthixol decanoate or haloperidol decanoate produces long-term changes in cocaine self-administration in rats.

The effect of decanoate forms of flupenthixol and haloperidol on cocaine self-administration was evaluated. Forty-two male Wistar rats were implanted with chronically indwelling jugular cannulae and trained to self-administer cocaine (0.6 mg/inj) either on a fixed ratio (FR) 1 schedule or a progressive ratio (PR) schedule. After a stable response pattern was established, animals received a single i.m. injection of either flupenthixol (2.0 mg), haloperidol (2.5 mg) or vehicle (0.1 ml oil). Both neuroleptics produced a long lasting increase in cocaine intake on a FR 1 schedule which reached a peak on post-injection day three and diminished slowly over the next seven days. All animals maintained on a PR schedule showed a long lasting decline in breaking points. These data suggest that the decanoate forms of flupenthixol and haloperidol may attenuate the reinforcing effects of cocaine and indicate that the therapeutic value of depot neuroleptics as anti-cocaine treatments would depend on the economics of cocaine availability.

Animals↗
PubMed2005

Antimicrobial potentiality of the thioxanthene flupenthixol through extensive in vitro and in vivo experiments.

The antipsychotic thioxanthene flupenthixol, possessing a trifluoromethyl substituent at position 2, exhibited a distinct antibacterial property against 352 strains of bacteria from 3 Gram-positive and 13 Gram-negative genera. The minimum inhibitory concentration (MIC) of flupenthixol was determined by the National Committee for Clinical Laboratory Standards agar dilution method. MICs ranged from 10-100 microg/mL in most of the strains, whilst some strains were inhibited at even lower concentrations. The mode of action of this drug was found to be bacteriostatic against Staphylococcus aureus and Vibrio cholerae. In the in vivo experiments, this drug was capable of contributing significant protection (P < 0.001) to a Swiss strain of white mice challenged with 50 median lethal dose of a mouse-virulent strain at a drug concentration of 15 microg/mouse. In addition, flupenthixol remarkably reduced the number of viable bacteria in organ homogenates and blood of mice treated with this drug.

Animals↗
PubMed2002

Association between flupenthixol treatment and emergence of manic symptoms.

BACKGROUND: Flupenthixol is an antipsychotic drug with known mood-elevating properties. Its propensity to induce manic symptoms has not been investigated. METHODS AND RESULTS: We describe six patients, four with schizophrenia and two with bipolar disorder, in whom flupenthixol treatment was associated with emergence of manic symptoms. CONCLUSIONS: Patients treated with flupenthixol should be carefully monitored for the emergence of manic symptoms.

Adult↗
PubMed2000

Flupenthixol as a potential pharmacotreatment of alcohol and cocaine abuse/dependence.

Preclinical and clinical studies suggest that the mesolimbic dopamine system plays a major role in mediating the reinforcing effects of drugs of abuse, including alcohol and psychostimulants, and that pharmacological blockade of dopamine D1 and/or D2 receptors may reduce intake of these drugs, as well as relapse rates. The neuroleptic flupenthixol, which has dopamine D1 and D2 receptor antagonist properties and which may be given intramuscularly in order to improve compliance, has been studied as a possible anti-craving drug in substance abuse disorders. Flupenthixol has been shown to attenuate the discriminative stimulus effects of psychostimulants, as well as their intake in animal models of drug abuse. In addition, the compound was found to reduce alcohol intake in a rat model of alcoholism, but the 'anti-alcohol' effect appeared to be only weakly selective and nonspecific. Clinically, the drug has been studied in alcoholics, cocaine addicts and in patients with comorbid psychiatric disorders. Although the data base is still limited and a number of recent trials have not been completely analyzed, these studies suggest that flupenthixol may be useful in decreasing cocaine consumption. Recent studies in alcoholism, however, have shown disappointing results. A number of pilot studies suggest that probably the most promising area may be the treatment of substance abuse/dependence in patients with comorbid psychiatric disorders. Future studies should focus on dosing issues, the differentiation between short- and long-term effects and the identification of subgroups of patients with particular psychopathology.

Alcoholism↗
PubMed1997

Tolerability of low dose neuroleptics: a case control study of flupenthixol.

There are no data available on the risk of extrapyramidal symptoms when using long-term flupenthixol in low dosage in patients suffering from anxiety and depressive disorders. In a case control study 106 patients essentially treated with the neuroleptic flupenthixol in a so-called low, non-antipsychotic dosage were compared to n=37 otherwise comparable patients who never had been treated with neuroleptics. The investigator was blind to the previous treatment conditions. Extrapyramidal symptoms were found although with a low prevalence and mild degree: 6.7% tardive dyskinesia, none in controls; pseudoparkinsonism 26%, 16% in controls. Extrapyramidal side-effects, especially tardive dyskinesia, have to be considered in the individual weighing of therapeutic benefits and risks even when prescribing flupenthixol in low dosages.

Adult↗
PubMed1992

Treatment of generalized anxiety disorder: comparison of a new beta-blocking drug (CGP 361 A), low-dose neuroleptic (flupenthixol), and placebo.

In an attempt to evaluate an alternative drug treatment to benzodiazepines in generalized anxiety disorders, a placebo controlled trial was carried out with a new beta-adrenergic blocker (CPG 361 A). A low-dosage neuroleptic (flupenthixol) was included as a reference drug. Depending on the clinical assessment scales the placebo treatment resulted in moderate to excellent improvement in 36% to 56% of the patients after four weeks of treatment. The active drugs generally had a higher improvement range (from 31% to 80%). The global improvement scale was found to be better than the other scales in discriminating between placebo (50% improvement) and the active drugs (CGP 361 A brought about 78% improvement and flupenthixol brought about 80% improvement). However, only for flupenthixol was the difference of statistical significance.

Adrenergic beta-Antagonists↗
PubMed2004

Flupenthixol and cefotiam: effects on vitamin A metabolism in rats.

We examined the alterations in vitamin A metabolism as a result of flupenthixol or cefotiam administration. The impact of these drugs on indices of vitamin A status was evaluated in Brown Norway and Long-Evans rats. Intramuscular drug administration for 28 d resulted in a decline in systemic retinol. Changes in circulating retinol with time for chronic dosing showed drug treatment (P<0.001) and time (P<0.03) to be significant factors, but rat strain (P=0.33) was not a significant factor. Flupenthixol was the most active retinol-lowering compound (P<0.005). At the end of the 28 d period, hepatic retinyl ester hydrolase activity was greater in drug-treated rats than in controls (P<0.05). With regard to effects on liver reserves: (1) flupenthixol treatment resulted in vitamin A depletion (P<0.05); (2) cefotiam treatment stimulated vitamin A accumulation; (3) distinctive patterns of retinol and its esters were seen in response to treatment. It is reasonable to assume that the drugs interfere with vitamin A in at least two ways: (1) lowering of plasma retinol, an early event in the interaction, may be caused by inhibition of hepatic holo-retinol-binding protein secretion or stimulation of clearance, or both; (2) when plasma retinol levels are persistently low, and as the hepatic deposits of the xenobiotics build up, there are changes in the vitamin A pool size and composition of the liver. Candidate enzymes are retinyl ester hydrolase and cytochrome P450. The relationship between these two events will be studied in further detail.

Animals↗
PubMed1987

The effects of a 50% reduction of cis(z)-flupenthixol decanoate in chronic schizophrenic patients maintained on a high dose regime.

Eighteen chronic schizophrenic patients who had shown improvement from increased maintenance dosages of cis(z)-flupenthixol decanoate were entered into a double-blind study in which half of the patients were randomly allocated to be maintained on 50% of their pre-trial dosage. During the 44 week study the reduced dosage group showed increased morbidity and one-third of these patients had a schizophrenic relapse. The greatest deterioration occurred in patients reduced from above to below 200 mg cis(z)-flupenthixol decanoate biweekly. A review of all the patients entered into the study showed a relationship between deterioration of schizophrenic and depressive features and cis(z)-flupenthixol plasma levels which reflected the administered dosage. Prolactin levels in general did not reflect control of schizophrenic symptoms. Side-effects were few, and there was no emergence of tardive dyskinesia. A multicentre trial is needed for further evaluation.

Adult↗
PubMed1999

Auto-amputation of the tongue associated with flupenthixol induced extrapyramidal symptoms.

We report a case of tongue auto-amputation in a mentally retarded patient after a flupenthixol injection. Four days after flupenthixol administration, the patient developed orolingual dyskinetic movements involving mainly tongue biting and protrusion. Self-mutilation in this case may be secondary to flupenthixol induced acute atypical orolingual dyskinesia in the face of mental retardation.

Adult↗