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At least 19 recordsLinked to original sources
PubMed1997

Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene.

1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a long-acting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance. 3. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. 4. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). 5. It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.

Adenosine↗
PubMed2002

Inhibition of glutamate release by fluspirilene in cerebrocortical nerve terminals (synaptosomes).

Fluspirilene, a neuroleptic drug which is used clinically to treat schizophrenic patients, is a dopamine D2 receptor antagonist. Besides its well-known actions on the dopamine receptors, fluspirilene also displays calcium channel-blocking activity. The aim of this study was to investigate the effect of fluspirilene on the 4-aminopyridine (4AP)-evoked glutamate release in the cerebrocortical nerve terminals (synaptosomes). Fluspirilene reduced 4AP-evoked glutamate release in a concentration-dependent manner. This inhibitory effect was associated with a decrease in the depolarization-evoked increase in the cytoplasmic free Ca2+ concentration ([Ca2+]C), which could be completely abolished by the Ca2+ channel blocker omega-CgTX GVIA. Furthermore, fluspirilene did not produce any effect on ionomycin-evoked glutamate release. These results suggest that fluspirilene inhibits glutamate release primarily by reducing presynaptic Ca2+ influx via N-type Ca2+ channels in rat cerebrocortical nerve terminals. This finding implies that presynaptic Ca2+ channel blockade concomitant with inhibition of glutamate release and possibly other neurotransmitters release may contribute to the antischizophrenic action of fluspirilene.

4-Aminopyridine↗
PubMed1990

Safety of long-term neuroleptanxiolysis with fluspirilene 1.5 mg per week.

In recent years concern has been frequently expressed that a long-term treatment with fluspirilene 1.5 mg/week might induce tardive dyskinesia, yet there are no empirical data from controlled studies available. In 11 private practices 276 patients under long-term treatment with either fluspirilene or benzodiazepines for reasons of anxiety or psychoneurotic or psychosomatic disorders were investigated by an independent and specially trained physician from our hospital with regard to symptoms to tardive dyskinesia, parkinsonism, and akathisia. Of these patients, 155 had received fluspirilene 1.5 mg/week with a mean duration of treatment of 17.5 months (s = 13.3), and 121 had received benzodiazepines with a mean duration of treatment of 45.7 months (s = 44.6). The mean total scores of the AIMS, the Simpson Angus Scale, and an akathisia scale did not differ significantly between the two groups. In the fluspirilene group a positive correlation of age and psychotropic comedication with the total scores of the AIMS and the akathisia scale could be found, but there was no correlation between duration or continuity of treatment with fluspirilene and symptoms of tardive dyskinesia. In each of the two groups 10 patients (6.9% of the fluspirilene group and 8.3% of the benzodiazepine group) showed abnormal involuntary movements, which corresponds to the incidence of spontaneous dyskinesia. The results of this study do not indicate an increase in tardive dyskinesia for patients with a mean duration of treatment with fluspirilene 1.5 mg/week of 18 months.

Akathisia, Drug-Induced↗
PubMed2000

Depot fluspirilene for schizophrenia.

BACKGROUND: Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as fluspirilene are extensively used as a means of long-term maintenance treatment. OBJECTIVES: To assess the effects of depot fluspirilene versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies. SELECTION CRITERIA: All relevant randomised trials focusing on people with schizophrenia where depot fluspirilene, oral anti-psychotics or other depot preparations were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data, Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. MAIN RESULTS: Seven studies were included. Most comparisons included very few participants. There are no convincing data showing fluspirilene decanoate's advantage over oral chlorpromazine or other depot antipsychotics. No study reported on hospital and service outcomes or commented on participants' overall satisfaction with care. Economic outcomes were not recorded by any of the included studies. REVIEWER'S CONCLUSIONS: The total numbers in each comparison were small and there were no clear differences demonstrated between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots, cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice.

Antipsychotic Agents↗
PubMed1990

Selective antagonism of calcium channel activators by fluspirilene.

1. Fluspirilene has been claimed to bind to a high affinity site in the calcium channel in skeletal muscle. We have investigated its calcium-antagonistic effects in smooth muscle and affinity for the channel in radioligand binding assays. 2. Fluspirilene was weakly active as an antagonist of Ca2(+)-induced contractions in K(+)-depolarized taenia preparations from the guinea-pig caecum, with threshold antagonism starting from concentrations of 30 nM. Nitrendipine, nicardipine and nimodipine were very potent antagonists in this model (threshold antagonism, greater than 1 nM). 3. In contrast, fluspirilene (10-1000 nM) was a potent non-competitive antagonist of the effects of Bay K 8644 (1-3000 nM) on Ca2(+)-induced contractions and, at 10 nM, selectively antagonised the effects of Bay K 8644, abolished the Ca2(+)-channel activator effects of CGP 28392, without changing the calcium antagonist effects of nitrendipine, or modifying the sensitivity of the tissues to Ca2+. In contrast, the dihydropyridines were more effective as antagonists of Ca2+ than of Bay K 8644. Fluspirilene therefore selectively antagonised the effects of dihydropyridine Ca2+ channel activators without affecting the antagonist potency. 4. In radioligand binding experiments, fluspirilene was a potent displacer of [3H]-PN-200-110 binding to rat cerebral cortical membranes (EC50 30 nM), albeit with a low Hill slope (0.66), and was more potent than other lipophilic diphenylalkylamines such as flunarizine and lidoflazine. Fluspirilene interacted non-competitively with [3H]-PN-200-110 and increased dissociation of the radioligand.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1978

Double-blind therapeutic evaluation of fluspirilene compared with fluphenazine decanoate in chronic schizophrenics.

Fifty chronic schizophrenics were randomly assigned to a 16-week treatment either with fluspirilene or with fluphenazine decanoate. The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics. Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor, severe extrapyramidal effects and parkinsonism. More patients in the fluspirilene group (nine patients) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial. Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group. The improvement in the NOSIE-30 was much more clear in the fluspirilene group. Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene, the differences between the two groups were not statistically significant.

Adult↗
PubMed1989

Utilization and safety of fluspirilene in nonpsychotic outpatients.

Over a six-month period, the utilization and safety of fluspirilene were investigated in 230 nonpsychotic outpatients in twelve private psychiatric practices. The patients treated under routine treatment conditions were about 20 years older than those included in experimental studies with this drug. In contrast to expert recommendations, 21.7% of the patients had received repeated injections of fluspirilene for longer than three months. A total of 46.1% of patients had been comedicated from time to time with antidepressants, while 30% had received benzodiazepines, indicating that fluspirilene is used as an alternative, but also as a supplementary treatment to benzodiazepine tranquilizers. Adverse reactions, probably related to fluspirilene, were recorded in 8.7% of patients and led to discontinuation of treatment in 3.9%. Disturbances of the extrapyramidal system predominated (in 5.6% of patients), with akathisia being observed most often (in 3.5%). It is concluded that the application of fluspirilene would seem to be safe if the drug is administered in the recommended way, but that there is a risk of tardive dyskinesias in the case of higher doses, longer duration of use, or pre-existing cerebral lesions (as manifested by two patients included in this survey).

Adolescent↗
PubMed1995

[Interaction of therapeutic effects and side effects in drug therapy of generalized anxiety disorders with low dosage fluspirilene].

The present study was designed to investigate the interaction between therapeutic effects and side-effects in fluspirilene treatment of generalised anxiety disorders (GAD). 205 outpatients received in an open trial 1.5 mg fluspirilene per week for 6 weeks. Confirming previous reports of our study group fluspirilene demonstrated marked efficacy and was generally well tolerated. However, the main finding of our study is that side effects, although rare in fluspirilene treatment, predict an unfavourable clinical outcome. This phenomenon is integrated in a psychological model implying that when GAD patients are aware of side-effects this induces anxiety. Again anxiety gives rise to somatic symptoms, both interacting in a forward loop. In conclusion, our data suggest that in the sense of Heinrich (1988) fluspirilene treatment of GAD should be guided by paying attention to possible side effects.

Adolescent↗
PubMed1986

A controlled clinical trial of fluspirilene, a long-acting injectable neuroleptic, in schizophrenic patients with acute exacerbation.

A 4-week double-blind controlled clinical trial was carried out in which fluspirilene, an injectable diphenylbutylpiperidine neuroleptic given weekly, was compared to chlorpromazine in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. Similar therapeutic improvement was obtained with both drugs, but men needed a significantly higher mean dose of fluspirilene (23 mg/week) than women (13 mg/week). Fluspirilene induced more parkinsonism than chlorpromazine, but less drowsiness, dizziness, and dry mouth. The difference between the sexes in the potency of fluspirilene and its greater potential to induce parkinsonism may be related to its lesser presynaptic and D1-dopamine receptor blocking properties. The low incidence of autonomic side effects confirms the relative specificity of fluspirilene for dopamine receptors.

Adult↗
PubMed1984

[Alternative therapy concept for the treatment of psychosomatic disorders. Controlled double-blind evaluation of fluspirilene versus bromazepam].

Today, Fluspirilene 1.5 mg i.m. (Imap 1,5 mg), is used to treat psychosomatic conditions, anxiety states and psychogenic disorders. The present article reports on clinical studies involving these indications. The efficacy of Fluspirilene 1.5 mg i.m. was demonstrated in patients with functional organic complaints, autonomic emotional symptom complexes, patients with anxiety, patients with functional heart complaints, and patients with functional gynaecological disorders. The results of a controlled study of 1.5 mg Fluspirilene i.m. and 6 mg Bromazepam are discussed. Forty-five patients from a neurologist's practice participated, all of whom had been classified as treatment-requiring patients with neurotic anxiety, on the basis of the physician's diagnosis and psychometric examination. Treatment lasted 42 days. The clinical assessment by the physician revealed that 1.5 mg Fluspirilene i.m. is significantly more effective than Bromazepam. The psychometric findings showed that patients with marked somatic anxiety treated with Fluspirilene showed greater improvement as expressed in a reduction in anxiety, lightening of mood, and increased activity, as compared with Bromazepam.

Adult↗
PubMed1994

[Severe "late" dystonia after neuroleptic anxiolysis with fluspirilene].

The development of severe tardive dystonia after short-term use of low-dose Fluspirilen is described. A 39-year-old woman was treated with Fluspirilen IM by her family doctor for reactive depression. She did received no other neuroleptic agents and no risk factors for the development of tardive dyskinesia (e.g. old age or organic brain damage) were present. For the first time a relation between short-term monotherapy with Fluspirilen and tardive dyskinesia appears highly probable. The use of Fluspirilen for the treatment of psychogenic disturbances should therefore be considered carefully.

Adjustment Disorders↗
PubMed1990

GBR-12909 and fluspirilene potently inhibited binding of [3H] (+)3-PPP to sigma receptors in rat brain.

Fluspirilene and GBR-12909, two compounds structurally similar to BMY-14802 and haloperidol, were assessed for their ability to interact with sigma receptors. Fluspirilene, an antipsychotic agent that interacts potently with dopamine receptors, inhibited the binding of [3H]-(+) 3-PPP (IC50 = 380 nM) more potently than rimcazole, a putative sigma antagonist that was tested clinically for antipsychotic activity. GBR-12909, a potent dopamine uptake blocker, also inhibited the binding of [3H]-(+) 3-PPP with an IC50 of 48 nM. However, other compounds that block the re-uptake of catecholamines, such as nomifensine, desipramine, imipramine, xylamine, benztropine and cocaine, were much weaker than GBR-12909 as sigma ligands. Thus, GBR-12909 and fluspirilene, compounds structurally similar to BMY-14802, are potent sigma ligands.

Animals↗
PubMed1998

Determination of fluspirilene in human plasma by liquid chromatography-tandem mass spectrometry with electrospray ionisation.

An ultra-sensitive method for the determination of fluspirilene in plasma was established, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. The samples were extracted with hexane/isoamyl alcohol, separated on a Phenomenex Luna C18 5 mu 150 x 2.1 mm column with a mobile phase consisting of methanol-water-acetic acid (600:400:1) at a flow-rate of 0.3 ml/min. Detection was achieved by a Finnigan Matt mass spectrometer (LCQ) at unit resolution in full scan mode scanning the product ion spectrum from m/z 130-500 and monitoring the transition of the protonated molecular ion at m/z 476.2, to the sum of the largest product ions m/z 371, 342 and 274 (MS-MS). Electrospray ionisation was used for ion production. The mean recovery for fluspirilene was 90% with a lower limit of quantification of 21.50 pg/ml using 1 ml plasma for extraction. This is the first chromatographic method described for the determination of fluspirilene in plasma that is accurate and sensitive enough to be used in pharmacokinetic studies.

Antipsychotic Agents↗
PubMed1979

[A comparative study of the longacting neuroleptics perphenazin-enanthate and fluspirilene (author's transl)].

The clinical profile and side-effects of perphenazin-enanthate and fluspirilene were compared in 45 female chronic schizophrenic patients. 100 mg perphenazin-enanthate fortnightly or 8 mg fluspirilene weekly were administered. During the four months' period the psychopathological and somatic symptoms were evaluated by means of the AMP-system and the self-evaluation scale PD-S (v. Zerssen). A covariance analysis was carried out covering 12 AMP syndromes and 6 PD-S factors. The antipsychotic effect of both drugs was similar concerning the paranoid, the hallucinatory-desintegrative and the catatonic syndromes. A significant difference with regard to perphenazin-enanthate was found in the AMP-syndromes of hostility, hypochondria, and autonomic symptoms. Neither drug induced any depression. In the self-rating scale, the factors anxiousness and depressivity were also significantly lower in the perphenazin-enanthate regime. The patients under perphenazin-enanthate required a smaller amount of antiparkinsonian drugs. The more pronounced sedative effect of perphenazin-enanthate can be recommended in hostile and restless schizophrenic patients, whereas fluspirilene should be given to inactive autistic patients.

Chronic Disease↗
PubMed1985

Experimental comparison of low doses of 1.5 mg fluspirilene and bromazepam in out-patients with psychovegetative disturbances.

In order to find out whether the administration of bromazepam and low doses of fluspirilene for six weeks had different effects, 45 out-patients of both sexes received 6 mg bromazepam per day or 1.5 mg fluspirilene per week in a double-blind randomized fashion. Overall therapeutic effectiveness was rated by the physician in two weeks' intervals. In addition use was made of the Hamilton Anxiety Scale, the Adjective List (Janke and Debus), and the Symptom Check List (Derogatis). Both products reduced anxiety in a comparable manner. Under fluspirilene, however, global therapeutic improvement was often more obvious than under bromazepam. This therapeutic superiority was particularly remarkable in patients whose somatic concern in the meaning of the Hamilton Anxiety Scale was comparatively pronounced.

Adult↗
PubMed1982

A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia.

A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one.

Adult↗
PubMedDate not supplied

A double-blind clinical evaluation of different dose intervals with fluspirilene (IMAP).

The possibility of a biweekly dose of fluspirilene, without deterioration of the clinical picture, was investigated in a group of 34 chronic schizophrenic patients. There were no significant clinical difference between the patients receiving fluspirilene every week and the patients receiving it every two weeks. Therefore it is possible to give fluspirilene in individually adjusted doses with a dose interval of 14 days in stabilized patients.

Adolescent↗
PubMed1995

Test therapy in the treatment of generalized anxiety disorders with low dose fluspirilene.

1. The present double-blind study was designed to determine under three different conditions (0.5 mg, 1.0 mg, 1.5 mg per week) whether response or non-response within a two-week test-therapy predicts clinical outcome after 6 weeks of fluspirilene treatment in generalized anxiety disorders. 2. 106 outpatients entered the study. The period of observation was 6 weeks. 3. Confirming previous reports of their study group the authors found a significant reduction of anxiety in all treatment groups. However, this effect was mainly observed with the highest dose administered. The main finding of the study is that there is a significant correlation between initial response after 2 weeks of test therapy and therapeutic success after 6 weeks in fluspirilene treatment of generalized anxiety disorders. 4. Decreases in somatic anxiety, psychic anxiety and Hamilton-total-score within the first 2 weeks correlate with the baseline-to-week 6 decreases of the corresponding item and with the global clinical assessment of efficacy after 6 weeks. 5. By means of test therapy patients with an unfavourable outcome are identified and, if medication is discontinued, are prevented from an ineffective longterm treatment.

Adult↗