Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-four chronic schizophrenic inpatients participated in this multicentre 12-week parallel-group double-blind trial. After a run-in period of 2 weeks and a single-blind placebo wash-out of 1 week, they were randomly assigned to treatment with either the serotonin2 and dopamine-D2 antagonist risperidone or haloperidol. Two patients were excluded from the efficacy analysis. Five patients dropped out in the haloperidol group and 1 in the risperidone group. At the end of the trial, the mean daily dose was 12 mg for risperidone and 10 mg for haloperidol. The risperidone group showed greater improvement on the Positive and Negative Syndrome Scale for Schizophrenia, the Schedule for Affective Disorders and Schizophrenia-change version, and the Nurses' Observation Scale for Inpatient Evaluation. The improvement of negative symptoms was more pronounced in the risperidone group until week 8 of double-blind treatment. The consumption of antiparkinsonian medication was 10 times lower with risperidone. Both drugs were well tolerated and the laboratory, endocrinological and cardiovascular safety parameters were comparable. This study suggests that risperidone is comparable to haloperidol as an antipsychotic, but that it has a safer EPS profile.
 ...
PMID:Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study. 137 1

Despite the considerable data generated thus far, a unifying theory for the role(s) of NT in the CNS has not been achieved. However, several conclusions with clinical relevance can be made about neurotensin. First, NT is intimately associated with the mesolimbic DA system and has the ability to selectively modulate this system. Second, NT possesses a pharmacobehavioral profile that is similar to antipsychotic drugs, with many similarities to the atypical class of antipsychotics drugs. If the pathogenesis of schizophrenia is related to dopaminergic hyperactivity, then the existence of an endogenous NT system that modulates the activity of the DA system, may represent a mechanism for the prevention of psychosis. The ability of the atypical antipsychotic drugs to effectively reduce the symptoms of schizophrenia does not depend entirely upon the blockade of D2 receptors, yet many of these drugs alter NT concentrations. The development of NT receptor agonists that can cross the blood brain barrier may prove valuable in the treatment of schizophrenia, while avoiding the liability of EPS and TD.
 ...
PMID:Neurotensin-dopamine interactions: relevance to schizophrenia and the action of antipsychotic drugs. 167 73

Shortly after the introduction of the first neuroleptics a serotonin hypothesis of schizophrenia has been proposed. But neuroleptics in animals and in man were found to produce effects more consistently related to inhibition of the dopaminergic than of any other type of neurotransmission. However, two early neuroleptics, pipamperone and clozapine, act pharmacologically more on 5-HT2 than on D2 receptors. Both have a distinct clinical profile and low EPS liability. The development of selective 5-HT2-antagonists, devoid of LSD-like properties, resulted in a first compound, ritanserin. Clinically, the highly specific 5-HT2-antagonism of ritanserin improves dysthymia, increases slow wave sleep and supports classical neuroleptic treatment by decreasing negative symptoms and EPS. These properties, being valuable by themselves, have been associated to dopamine D2-antagonism in the new antipsychotic risperidone, which is an extremely potent 5-HT2-antagonist. At doses of 5 mg daily risperidone acts on both negative and positive symptoms of schizophrenia in the virtual absence of EPS.
 ...
PMID:[Serotonin antagonism involved in the antipsychotic effect. Confirmation with ritanserine and risperidone]. 169 60

Pharmacological treatment of schizophrenia in based in the hypothesis that disturbances in central dopaminergic (DA) systems, i.e. increased DA-activity in the mesolimbic system, are involved in the pathogenesis of these psychotic disorders. Since neuroleptics exert a broad spectrum of pharmacological activities, during the last decade efforts have been undertaken to develop new antipsychotics, separating their antipsychotic action from their extrapyramidal (EPS) effects. Neuroleptics with this kind of properties have been designated atypical, although being a rather heterogenous group. In fact, some of the atypical antipsychotics are selective with respect to neurotransmitter system or regional brain activity like the benzamides, while others are non-selective at all such as the dibenzodiazepine derivate clozapine, and interfere with different receptor systems. In general, the atypical antipsychotics can be divided among two groups: DA-selective compounds and receptor non-specific agents. Of the DA-selective compounds, the group of the benzamides form a distinct chemical class, of which sulpiride has been the most thoroughly investigated, followed by remoxipride. Concerning the antipsychotic effects of the benzamides, sulpiride as well as remoxipride have been demonstrated to be equipotent as compared to classical neuroleptics like chlorpromazine and haloperidol, without however inducing either EPS or anticholinergic symptoms of importance. With respect to the dibenzodiazepine derivate clozapine, it has been demonstrated that this compound has not only potent antipsychotic properties but, more important, may be effective in severely ill treatment resistant patients, without most probably the risk of inducing EPS. Finally, the series of compounds, characterized by serotonin -S2- and dopamine -D2- antagonistic properties may be of importance, albeit they do not meet the presently common definition of atypicality.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Atypical neuroleptics. Review of the available clinical data]. 198 16

After a wash-out period of 1 week, 20 patients suffering from schizophrenia were treated for 4 weeks in an open dose-finding study with a new serotonin-dopamine antagonist risperidone. All patients completed the trial. The mean daily dose of risperidone was 4.6 mg (range 2-10 mg) at completion. Risperiodone had a rapid onset of action: a highly significant decrease of the total BPRS score (Brief Psychiatric Rating Scale) was already noticed at the end of the second week. This decrease was found in all BPRS factors after 4 weeks. In spite of the withdrawal of antiparkinson medication at selection, a clear decrease of EPS (extrapyramidal symptoms), assessed on the Simpson and Angus Scale, was observed. The Global Therapeutic Impression agreed to the BPRS scores, showing a highly significant improvement after 2 weeks of treatment. Risperidone was very well tolerated, only mild side effects were reported. Vital signs, electrocardiographic parameters and laboratory values remained normal during the trial. This study indicates that risperidone can be an effective and well-tolerated alternative in the treatment of chronic schizophrenia, combining an antipsychotic activity, a beneficial effect on anergia and anxiety depression and a low EPS-inducing profile.
 ...
PMID:The efficacy of the D2 and 5-HT2 antagonist risperidone (R 64,766) in the treatment of chronic psychosis. An open dose-finding study. 248 25

In the past 14 years pipotiazine palmitate, the second oldest depot neuroleptic, has proven to be effective and safe in reducing and preventing resurgence of symptoms of acute and chronic psychoses, chiefly in schizophrenia. It is particularly valuable in the management of erratic ingestors and unreliable absorbers of oral neuroleptics. Clinical experience substantiates that pipotiazine palmitate therapy is best initiated at low doses (25 mg), and that the most effective maintenance dosage is 25 to 200 mg once a month. Pipotiazine palmitate has a low propensity to evoke extrapyramidal reactions; in fact, it causes the lowest incidence of EPS of all depot neuroleptics. Patients receiving pipotiazine palmitate seldom require concomitant antiparkinsonian medication. This review highlights other assets and liabilities of depot pipotiazine therapy.
 ...
PMID:Depot pipotiazine 1970-1982: a review. 613 18

The discovery of chlorpromazine led to rapid progress in drug therapy for schizophrenia. However, conventional neuroleptics frequently induce EPS and tardive dyskinesia in addition to the drawback of having little effect against negative symptoms. New types of atypical antipsychotics has been actively developed in Japan to overcome these drawbacks. Firstly, serotonin-dopamine antagonist (SDA) is most actively developed. Eight SDAs have been introduced into clinical trials: risperidone's trials have been finished and a NDA has been filed, Org 5222 has been dropped because of worsening of significant cases, and 6 SDAs (SM-9018, sertindole, seroquel, AD-5423, ziprasidone and olanzapine) are now under development. Secondly, OPC-14597, a unique atypical antipsychotic has been advanced to the phase 3 study, which has both DA autoreceptor-agonistic and D2-receptor blocking actions. Thirdly, we have much interest in NE-100, a selective sigma receptor antagonist which potently suppresses the phencyclidine-induced behaviors. Finally. a 5-HT3 receptor antagonist, alosetron was already dropped because it showed no antipsychotic effects, although it was introduced with great expectations. We hope that as many as possible new antipsychotics will be approved for the battle against schizophrenia.
 ...
PMID:[Recent progress in development of psychotropic drugs (2)--antipsychotics]. 758 13

The side effects of antipsychotic drugs have always been a major concern for clinicians and the appreciation of their importance in the treatment of schizophrenia has increased steadily over the years. Epidemiological studies as well as trials of the prevention and treatment of antipsychotic side effects are the consequences of this development. Results of these studies also have important implications for improving compliance and quality of life in schizophrenic patients. Thus, side effects research has made the treatment of schizophrenia not only safer but also more effective. Next to a brief overview of some of the more important adverse events and their treatment, we will also discuss these effects in the context of compliance, treatment response and the influence of anti-EPS drugs.
 ...
PMID:Adverse effects of antipsychotic drugs. 762 30

Clozapine is a great advance in the treatment of schizophrenia. It should be tried in any neuroleptic-resistant schizophrenic as well as some who are neuroleptic intolerant. If progress is made in controlling its agranulocytosis, clozapine could be the drug of choice for all types of schizophrenia and perhaps other conditions as well for which neuroleptic drugs are employed, e.g., mania resistant to mood stabilizers. Its advantage with regard to lower risk of tardive dyskinesia indicates that potent antipsychotic activity and liability to cause tardive dyskinesia can be dissociated. This must be the object of future antipsychotic drug development. Risperidone could be the next clozapine but at the time of this writing, there is too little data to pass judgment on this. Its low EPS profile and apparent effects on negative symptoms at lower doses are promising. Remoxipride may be useful because of its low EPS profile. How much better tolerated it is than currently available drugs, especially thioridazine, is not clear. Many other novel agents are being tested. Clinicians will be challenged to follow this emerging field closely and identify the most promising new agents that may be indicated for specific stages of, or subtypes of, schizophrenia.
 ...
PMID:New drugs for the treatment of schizophrenia. 810 73

The results of an open tolerability and exploratory efficacy study of bretazenil, a partial benzodiazepine-receptor agonist in hospitalized schizophrenic patients with an acute psychotic episode (DSM-III-R criteria), are presented. The duration of the study was 6 weeks, with a mandatory titration (ascending doses of 3-18 mg/day) period of 14 days. The assessment criteria for tolerability were the frequency of adverse events (including EPS), vital signs and laboratory tests. The efficacy criteria, which were only descriptively analysed, were: (a) Clinical Global Impression (CGI, percentage of "very much" and "much" improvement); and (b) change in BPRS total score (e.g. percentage of patients showing > or = 40% decrease of BPRS score at the end of the treatment). Sixty-six patients (aged 21-62 years) with acute episodes of schizophrenia of moderate to marked severity (mean BPRS score = 46.3, range 26-76) were included in the study. Of these 66 patients (68%) were reportedly non-responders (n = 10) or partial responders (n = 35) to previous neuroleptic therapy. Twenty patients (30%) terminated the trial prematurely due to therapeutic failure (no improvement or worsening after 2 weeks of treatment), 17% of patients dropped out due to other reasons (transfer to other hospitals, withdrawal of consent, intercurrent diseases) and 4.5% of patients stopped the treatment due to adverse reactions. Four patients (6%) showed early complete remission and refused to be further treated. The analysis of efficacy (intention-to-treat) revealed a sustained decrease of BPRS scores with 49% of patients showing > or = 40% BPRS score change by the end of the treatment. Forty-four per cent of patients improved "very much" or "much". Eleven patients (17%) were full responders (BPRS score decrease 75-100%) and 21 patients (32%) showed at least 40% reduction of BPRS score. The reduction of BPRS scores in completers only was 60%. All BPRS factor scores decreased in parallel and, particularly, no preferential decrease of anxiety/depression subscores was found. The analysis of tolerability showed that 59% of patients presented no complaints at all. The most frequent treatment-related adverse reactions in the remaining patients were: sedation (n = 14), dizziness (n = 4) and headache (n = 3). The results of this study suggest moderate antipsychotic efficacy of bretazenil in schizophrenic patients. They encourage further investigations of partial benzodiazepine-receptor agonists in this indication, particularly because of the excellent tolerability and lack of extrapyramidal side-effects.
 ...
PMID:Antipsychotic effects of bretazenil, a partial benzodiazepine agonist in acute schizophrenia--a study group report. 890 33


1 2 3 4 5 6 Next >>