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The inhibition of tumor suppressor p53 protein due to its direct interaction with oncogenic murine double minute 2 (MDM2) protein, plays a central role in almost 50 % of all human tumor cells. Therefore, pharmacological inhibition of the p53-binding pocket on MDM2, leading to p53 activation, presents an important therapeutic target against these cancers expressing wild-type p53. In this context, the present study utilized an integrated virtual and experimental screening approach to screen a database of approved drugs for potential p53-MDM2 interaction inhibitors. Specifically, using an ensemble rigid-receptor docking approach with four MDM2 protein crystal structures, six drug molecules were identified as possible p53-MDM2 inhibitors. These drug molecules were then subjected to further molecular modeling investigation through flexible-receptor docking followed by Prime/MM-GBSA binding energy analysis. These studies identified fluspirilene, an approved antipsychotic drug, as a top hit with MDM2 binding mode and energy similar to that of a native MDM2 crystal ligand. The molecular dynamics simulations suggested stable binding of fluspirilene to the p53-binding pocket on MDM2 protein. The experimental testing of fluspirilene showed significant growth inhibition of human colon tumor cells in a p53-dependent manner. Fluspirilene also inhibited growth of several other human tumor cell lines in the NCI60 cell line panel. Taken together, these computational and experimental data suggest a potentially novel role of fluspirilene in inhibiting the p53-MDM2 interaction. It is noteworthy here that fluspirilene has a long history of safe human use, thus presenting immediate clinical potential as a cancer therapeutic. Furthermore, fluspirilene could also serve as a structurally-novel lead molecule for the development of more potent, small-molecule p53-MDM2 inhibitors against several types of cancer. Importantly, the combined computational and experimental screening protocol presented in this study may also prove useful for screening other commercially-available compound databases for identification of novel, small molecule p53-MDM2 inhibitors.

We describe a 62-year-old patient with a chronic delusional disorder who presented with severely matted hair ("plica polonica"). Until the late 19th century such dreadlocks were considered as cause, consequence and treatment of mental disease. The historical development of "plica polonica" is briefly reviewed as an example of early and once popular psychiatric disease concepts.

Background: Antipsychotic 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 review 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: We searched the Cochrane Schizophrenia Group's Register (September 2005), inspected references of all identified studies, and contacted relevant pharmaceutical companies., Selection Criteria: We included all relevant randomised trials focusing on people with schizophrenia where depot fluspirilene, oral anti-psychotics, other depot preparations, or placebo 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, we calculated relative risk (RR) with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. We summated normal continuous data using the weighted mean difference (WMD). We presented scale data only for those tools that had attained pre-specified levels of quality., Main Results: We included twelve randomised studies in this update of which five are additional studies. One trial compared fluspirilene and placebo and did not report important differences in the global improvement (n=60, 1 RCT, RR "no important improvement "0.97 CI 0.9 to 1.1). Though movement disorders (n=60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4) were found only in the fluspirilene group, there were no convincing data showing the advantage of oral chlorpromazine or other depot antipsychotics over fluspirilene decanoate. We found no difference between depot fluspirilene and other oral antipsychotics with regard to relapses or to the number of people leaving the study early. Global state data (CGI) were not significantly different, in the short term when comparing fluspirilene with other depots (n=90, 2 RCTs, RR "no important improvement" 0.80 CI 0.2 to 2.8). No significant difference were apparent between fluspirilene and other depots with respect to the number of people leaving the trial early (n=83, 2 RCTs, RR 0.55 CI 0.1 to 2.3) or relapse rates (n=109, 3 RCTs, RR 0.55 CI 0.1 to 2.3). Extrapyramidal adverse effects were significantly less prevalent in the fluspirilene groups (n=164, 4 RCTs, RR 0.50 CI 0.3 to 0.8, NNH 5). Other adverse effects were not significantly different. Attrition in the one comparison between fluspirilene in weekly versus biweekly administration (n=34, RR 3.00 CI 0.1 to 68.8) and relapse rates (n=34 RR 3.18 CI 0.1 to 83.8) were not significantly different. There were no significant difference for movement disorders in one short term study. 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., Authors' Conclusions: Participant numbers in each comparison were small and we found no clear differences 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.

An inquiry into the psychopathology and the clinical significance of grief hallucinations is presented and two cases with severe grief hallucinations are described. Unlike many cases in the literature, the two female patients were young (aged 43 and 45, respectively) and both suffered from the loss of a daughter. The heterogeneous concept of grief hallucinations is described and discussed, focusing particularly on the difficulties of reaching a differentiation between hallucination and pseudohallucination. Basic theses of the article are: (1) Contrary to a widely held view, grief hallucinations can display all the characteristics of 'true' hallucinations. (2) The concept of grief hallucinations probably comprises a heterogeneous group of disturbances of perception and of thought processes. They can be experienced as comforting but can also cause considerable distress. (3) There are essentially two definitions of pseudohallucinations and they contradict each other. The extremely vague concept of pseudohallucinations appears to be of questionable value and should be abandoned., (Copyright 2002 S. Karger AG, Basel)

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.

1. The present study was designed to determine the impact of neuroleptic side effects on clinical outcome in generalized anxiety disorder. 2. 205 outpatients entered the study. In an open label design fluspirilene 1.5 mg per week was administered for a period of 6 weeks. 3. Consistent with previous studies fluspirilene demonstrated again anxiolytic properties and was in general tolerated well. 4. However, in responders significantly less side effects were observed than in nonresponders. The interaction between tolerability and clinical outcome is the main finding of the present study. 5. In conclusion, the data suggest, that neuroleptic treatment of generalized anxiety disorder should be guided by paying more attention to potential side effects. If under neuroleptic treatment of generalized anxiety disorders side effects are observed, pharmacotherapy should be discontinued, because this fact predicts an unfavourable clinical outcome.

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.

1. In order to prove that neuroleptanxiolysis represents a therapeutical alternative in the treatment of patients suffering from anxiety we conducted four investigations. 2. In the first study it was experimentally proved with 45 outpatients suffering from anxiety that fluspirilene (1.5 mg per week) is superior to bromazepam (6 mg/day), especially in patients with a high degree of somatic anxiety. 3. In the second study the tolerance of fluspirilene (1.5 mg per week) was investigated in 1261 patients with anxiety states and psychoreactive disorders under controlled and open conditions for a period of six weeks. Side effects were found in 11.5% of the patients. All side effects had in common that they occurred already within the first few weeks of treatment. 4. In the third study investigating the dose-effect relationship 106 patients received either 0.5, 1.0, or 1.5 mg fluspirilene per week for a period of 6 weeks. The main result of this study was the verification of a clear dose-effect relationship. 5. The fourth study compared 155 patients who had received long-term treatment with fluspirilene (max 1.5 mg/week) and 121 patients with long-term benzodiazepine treatment. No differences were found with regard to the frequency and intensity of extra-pyramidal disturbances. 6. The therapeutical relevance of the findings was emphasized in the general discussion.

In recent years, depot neuroleptics have gained in importance in the outpatient treatment of chronic schizophrenics. These neuroleptics make drug therapy safer than before, thus improving the prerequisites for socio-therapeutic and rehabilitative measures. The present study analyses the ranking and value of this kind of treatment in the management of outpatients. A random sample of 80 schizophrenics treated as outpatients, by a psychiatric university clinic working on a sectorial basis was examined for the purpose of this study. Treatment results, problems of indication, limitations of therapeutic possibilities using depot neuroleptics, as well as constellative conditions under which therapy was discontinued, are discussed.

The differences in the psychopathologic status of 26 complaint and 32 noncomplaint schizophrenic patients were evaluated on the basis of rating scales used at discharge. Noncomplaint patients had significantly higher scores for grandiosity, lack of feeling of illness and insight into it. Their score for global psychopathological state and disturbance in social adjustment was also significantly higher. The compliant patients had significantly higher score for self-rated depression.

Fluspirilene proved to be a very useful drug in the basic maintenance therapy of 21 chronic schizophrenic patients (ages 16-71 years), who received individually adjusted doses weekly during their hospitalization and during the subsequent follow-up period. The follow-up data analysis showed that the antipsychotic efficacy of the drug after prolonged (8-21.5 months) treatment was nicely maintained, that the patients' socio-professional integration had improved significantly, while a small decrease in dosage proved possible in several cases. The incidence of side-effects remained low, and no signs of accumulation or toxicity could be detected.

A group of 82 nonselected patients with the leading symptom "anxiety" as part of psychoreactive disturbances was included in a study comparing the effectiveness of fluspirilene and bromazepam. The results of an earlier pilot study showing on the whole the superiority of fluspirilene versus bromazepam was confirmed. The absence of significant side-effects under either medication seems to indicate, that the administration of the low-dose long-acting neuroleptic might be a preferable alternative to tranquilizers, especially in patients, in whom a danger of misuse cannot be excluded.

Over a period of 7 to 12 weeks we studied 3 series of 274 patients with depressive and somatic complaints treated with the long-acting neuroleptic fluspirilene in a dosage of 1-1.5 mg weekly. By means of various rating scales it was compared to diazepam in regard to its tranquilizing effects. Fluspirilene showed good activating and antidepressive qualities, which were superior to those of diazepam, whereas somatic complaints responded equally well to both drugs. The indications for a long-acting tranquilizer with the advantage of a controllable application are being discussed.

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.

Patients with psychosomatic complaints of a hypochondriacal nature were treated with a weekly IM dose of 1.2-1.5 mg fluspirilene (0.6-0.75 ml IMAP) for a period of 10 weeks. According to the physicians' ratings, good results were obtained in 58%, moderate ones in 28%. In the patients' ratings, this corresponded to 60 and 26% respectively. Acceptability of the treatment was assessed as good by 88% of the physicians and 90% of the patients. Only two side effects were reported by three patients alike (dry mouth and sweating). The other side-effects were rarer in occurrence and half of them were transient.

Over a period of 8 weeks we compared the tranquilizing effects of the longterm neuroleptic Fluspirilene to those of Diazepam in a series of 28 patients. Both drugs showed good effects on somatization, anxiety and depressive mood. Fluspirilene, however, proved to be the more mood elevating and more activating agent without being hypnotic. The indications for both drugs are being discussed emphazising the new therapeutic perspectives of a long acting tranquilizer.

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.

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.

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.

The paper reports on an open study of flupirilene administration in ten previously untreated female outpatients with paranoid symptomatology who were of advanced age. In eight of the ten patients who had been included in the 12-week study the authors observed a remission particularly of delusion dynamics, delusional intuitions, delusional perceptions, and restlessness as well as excitment. The therapy failed in two patients. Preexisting cerebro-organic impairments deteriorated partly, whereas vegetative and extrapyramidal side effects were of only moderate intensity. Hence, fluspirilene proved to be a depot neuroleptic with good antipsychotic effect in outpatient treatment of paranoid psychoses of patients of advanced age. However, especially in patients of advanced age. However, especially patients with preorganic brain syndrome, the obviously sedating and retarding effects of this drug must be taken into account, since they may contribute to further disturbance of the impaired cerebral function.

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).

A study was carried out to assess the efficacy of fluspirilene, a long-acting psychotropic agent, in the treatment of 29 non-hospitalized schizophrenic patients. Patients received an initial weekly injection of 6 mg to 10 mg fluspirlene, depending on the severity of the illness, and this was increased by 2 mg weekly as necessary to achieve control without side-effects. The mean weekly dose after stabilization was 9.2 +/- 3.4 mg (range 6 mg to 20 mg). Global assessment of patients' response to treatment showed a significant improvement in schizophrenic symptoms within 4 weeks in 20 of the 29 patients, and in 24 of 29 by the end of the 12-week trial period. Four patients were unable to be controlled in the community and were admitted to hospital. Side-effects were minimal and led to withdrawal of treatment in only 1 patient. It is suggested that fluspirilene is a useful drug in the treatment of schizophrenics without having to admit them to hospital initially.

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.

The authors discuss the historical aspects, as well as the various etiological and clinical factors which contribute to the so-called pharmacogenically induced depressions during treatment by means of neuroleptics generally, and long-term neuroleptics especially. An open study on 161 schizophrenic patients treated by means of fluspirilene and 123 patients treated by means of penfluridol is described. A single blind trial on 48 patients, by means of fluphenazine-decanoate and flupenthixol-decanoate, which compares the possible depression-inducing or antidepressant activity of the above drugs, is presented. The criteria for evaluating drug-induced depressions and their two clinical types are discussed.

The authors report clinical experience from therapy with Orap-Janssen and Orap-Richter from 1968 to 1974. Excellent tolerance makes Orap particularly suitable for long-term maintenance therapy in schizophrenic psychoses. The evaluation is based on observations in 91 patients.

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.

Fluspirilene (Trademark Imap) is a depot neuroleptic agent for i.m. injection known for several years. Since it is well tolerated, has substance-specific repository properties and rarely leads to extrapyramidal motorial side effects, it has proved itself efficient for the in- and outpatient treatment of psychoses. Recently however, an extension of its indication has been advocated (as a "weak tranquilizer") to unspecific anxiety and agitation states as well as functional/neurasthenic syndromes. According to our observations, administration of the drug over several weeks in these cases frequently leads to depressive syndromes. Based on three case studies, this paper illustrates the problems involving administration of 1,5 mg Imap in functional/neurasthenic syndromes and discusses the occasional necessity of antidepressive therapy following discontinuation of the neuroleptic medication.

In order to investigate the effects of 6 weeks' neuroleptic treatment on the pituitary-thyroid axis in 25 male schizophrenic patients, and the diurnal variation in the thyrotropin (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) in these patients, the TRH stimulation test was performed in each of them at 14.00 and 24.00 h of the same day, both before and after 6 weeks' treatment with neuroleptics (chlorpromazine or fluspirilene). Also, serum thyroxine (T4), in vitro radioactive triiodothyronine uptake (RT3 U) and free-thyroxine index (FTI) values were estimated from the pre-TRH blood sample. We found no evidence of diurnal variation in the TSH response to TRH in the schizophrenic patients, before or after 6 weeks' neuroleptic treatment. Only drug-free schizophrenic patients had significantly higher PRL responses to TRH at 14.00 h than those at 24.00 h. After 6 weeks' neuroleptic treatment, schizophrenic patients tended to have lower FTI values; also, they had significantly higher basal TSH and PRL values, as well as significantly augmented TSH and PRL responses to TRH, in comparison to their pretreatment values. These findings render possible the diagnosis of subclinical hypothyroidism in neuroleptic-treated schizophrenic patients.

The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way.

In 14 schizophrenic patients, treated with neuroleptic drugs, and in 7 patients, treated with high-dosage diazepam, beta-endorphin-like immunoreactivity in plasma has been measured by use of a highly sensitive and relatively specific radioimmunoassay. Neuroleptic treatment induced a significant increase of beta-endorphin-like immunoreactivity (beta-ELI). The pharmacological and clinical implications of this finding are discussed. High-dosage diazepam treatment induces a slight reduction of plasma beta-ELI, a finding which is attributed to antistress effect of diazepam.