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)

This article reviews the definitions of negative symptoms and the deficit syndrome of schizophrenia, rating scale criteria (the Scale for Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale), Crow's Type II syndrome, and Carpenter's deficit syndrome in relation to the DSM-IV. The effectiveness of conventional neuroleptics against negative symptoms is still in question. Improvement in negative symptoms may occur in tandem with improvement in the florid symptoms of schizophrenia, but negative symptoms may be difficult to discriminate from the extrapyramidal side effects that are caused by conventional neuroleptics. In a multicenter trial comparing the novel antipsychotic risperidone with haloperidol and placebo in symptomatic schizophrenia, negative symptoms (assessed using the Positive and Negative Syndrome Scale) were reduced more by risperidone at a dose of 6, 10, and 16 mg/day than by placebo. Haloperidol at a dose of 20 mg/day was not significantly better than placebo. Risperidone 6 mg was the lowest dose that produced substantial change in negative symptoms and no increase in extrapyramidal symptoms and antiparkinsonian medication use.
 ...
PMID:Negative symptoms in schizophrenia: assessment of the effect of risperidone. 752 Sep 5

In the study the usefulness was assessed of haloperidol depot preparation in 50 mg ampoules produced by Warsaw Pharmaceutical Works POLFA in the treatment of schizophrenia. The study group comprised 30 patients, 12 females and 18 males, aged 18-70 years. Before haloperidol administration all other drugs were withdrawn. Haloperidol depot was injected intramuscularly after 7-10 days of oral administration of haloperidol. The injections were done at 3-week intervals during 26 weeks. The mean interval between the injections was 17.8 days, and the mean dose was 77.0 mg. The effectiveness of the drug was assessed using Overall scale (BPRS) measuring the intensity of 18 psychotic symptoms in the following weeks of the trial: 0, 1, 2, 3, 4, 7, 10, 13, 17, 20, 23 and 26. The depot haloperidol preparation (Decaldol) was studied assessing its effects on productive and defect symptoms and depression. The strongest effect was exerted on productive symptoms, less pronounced effect was on psychotic defects, and lowest on depression symptoms. Improvement of the psychosis was noted in 20 cases, deterioration in 8 and no change was observed in two patients. The present trial period was not completed by 19 patients, 6 due to psychotic deterioration, 5 patients had intense extrapyramidal adverse effects and in 2 cases worsening of mental condition was associated with adverse effects. In this subgroup of 19 patients 9 were improved, 8 were worse, and 2 had no change in relation to initial status. In the remaining 11 cases who completed the study only full of considerable improvement was found.
 ...
PMID:[Evaluation of clinical usefulness of decaldol (haloperidol decanoate) produced by WZF Polfa in Warsaw in long-term treatment of schizophrenia]. 765 93

The noncompetitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801) produced an interoceptive stimulus cue in rats trained to discriminate between MK-801 (0.075 mg/kg) and saline in a two-choice, discrete trial avoidance paradigm. Haloperidol (0.03-0.3 mg/kg) failed to antagonize the discriminative stimulus cue of MK-801, with all rats choosing the MK-801-appropriate choice lever. Higher doses of haloperidol (1.0 mg/kg) produced significant sedation such that the rats were unable to complete all the trials. In contrast, clozapine dose dependently antagoinzed the discriminative stimulus cue produced by MK-801. Clozapine at a dose of 3.0 mg/kg completely antagonized the stimulus cue produced by MK-801. Therefore, the discriminative stimulus cue produced by the noncompetitive NMDA antagonist MK-801 may be useful as an animal model for selecting novel drugs with potential efficacy for treatment-resistant schizophrenia.
 ...
PMID:Clozapine but not haloperidol antagonizes an MK-801 discriminative stimulus cue. 766 88

There are numerous preclinical screening procedures that are predictive of clinical efficacy for the positive symptoms of schizophrenia but no assays for the negative symptoms such as social withdrawal. In the social interaction test in rats, the atypical antipsychotic drug clozapine (10.0 mg/kg) and two putative atypical agents risperidone (0.0625 mg/kg) and HP 873 (0.5 and 1.0 mg/kg) significantly increased social interaction behaviors between pairs of unfamiliar but not familiar rats. The benzodiazepine diazepam (1.25-5.0 mg/kg) increased social behaviors in both paradigms. Haloperidol, chlorpromazine, raclopride, and SCH23390 decreased social behaviors in these assays. In vitro receptor binding studies revealed that only clozapine, risperidone, and HP 873 displayed dopamine to serotonin affinity ratios for both D2/5-hydroxytryptamine2(5-HT2)/ and D1/5-HT1A of greater than or equal to 12.9 and 1.0, respectively. The present study suggests that antipsychotic agents that may be effective in social withdrawal can be identified in this modified social interaction paradigm. Further, our data suggests that a compound's effectiveness for the treatment of social withdrawal is at least in part due to its relative affinity for binding to dopamine D1 and serotonin 5-HT1A receptors.
 ...
PMID:Effects of atypical antipsychotic agents on social behavior in rodents. 768 16

Both acute and long-term effects of haloperidol and clozapine on Fos-like immunoreactive nuclei in several rat forebrain areas were quantified. Rats were treated with saline (1 ml/kg.day, control), haloperidol (1 mg/kg.day) and clozapine (20 mg/kg.day) i.p. for 21 days. Two hours before perfusion fixation a single (acute treatment) or last (long-term treatment) dose of the drug was given. Drug-induced catalepsy and gain in body weight were also measured. A single dose of haloperidol produced large increases in Fos-like immunoreactive nuclei in the striatum, the nucleus accumbens and central amygdala. Following long-term treatment these increases were reduced in all nuclei studied, except the lateral septum. Acute clozapine treatment had slight (if any) effects on the number of Fos-like immunoreactivity-expressing nuclei in the striatum, but the increases in the nucleus accumbens, the lateral septum, the paraventricular and supraoptic nuclei of the hypothalamus and the central amygdala were substantial. Long-term clozapine treatment reduced the acute response significantly in all the areas except the nucleus accumbens. Both haloperidol and clozapine treatment reduced the weight gain of the rats. Haloperidol, but not clozapine, induced catalepsy that remained maximal during the long-term haloperidol treatment. These results indicate that in most brain areas high Fos-protein levels are not necessary to maintain antipsychotic activity or side-effects. The persisting effect of clozapine in the nucleus accumbens may be of significance to the efficacy of this drug in treatment-refractory schizophrenia.
 ...
PMID:Differential Fos-protein induction in rat forebrain regions after acute and long-term haloperidol and clozapine treatment. 773 11

In spite of extensive studies over the last 2 decades to find direct evidence in support of the dopamine hypothesis of schizophrenia, no undisputed experimental data has been obtained. In contrast, estimation of noradrenalin (another major catecholamine) and its metabolites in postmortem brain and in the cerebrospinal fluid appears to be producing consistent results. To understand the meaning of this change for the pathogenesis of the illness, we have carried out animal experiments in which reproducibility of schizophrenic signs and symptoms by noradrenergic dysfunction, and treatability of the disorder by modulation of noradrenergic activity were studied. First, psychophysiological signs in skin conductance responsiveness (nonhabituating or nonresponding change) and smooth pursuit eye movement (spiky or stepwise pursuit) could be reproduced by enhancing or suppressing central noradrenergic activity. Behavioral abnormalities resembling schizophrenic symptoms are known to be reproducible by over- or underactivity of the system (overarousal or underarousal syndrome). Secondly, the action of various drugs capable of modulating schizophrenic symptoms was analyzed in relation to noradrenergic activity. Haloperidol, in particular, had a potent suppressing effect on skin conductance activity (spontaneous fluctuation rate and habituation rate) when administered chronically, suggesting its inhibitory action on noradrenergic activity.
 ...
PMID:Possible noradrenergic dysfunction in schizophrenia. 785 11

Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.
 ...
PMID:Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action. 789 30

A study was conducted to survey the prescribing practices of neuroleptic doses in 100 consecutively hospitalized DSM-III-R schizophrenic patients. The relationship between doses and clinical and symptomatological variables was subsequently analyzed. Patients were evaluated through the Positive and Negative Syndrome Scale (PANSS). The peak mean dose in chlorpromazine equivalents was 1290 (range 250-7200). Haloperidol was the most commonly employed neuroleptic (67 patients). Neuroleptic doses were correlated with excitement, suspiciousness, hostility, uncooperativeness and poor impulse control. The neuroleptic doses administered in our hospital were similar to those found in other survey reports but higher than those recommended by the controlled dose-response studies. The correlation found between neuroleptic doses and symptoms of disruptive behavior suggests that we employed high-dose practices to treat the disruptive symptoms of schizophrenia. We concluded that it is useful to distinguish between the neuroleptic doses required to control the psychotic episode and those to treat the disruptive behavior.
 ...
PMID:Neuroleptic dose and schizophrenic symptoms. A survey of prescribing practices. 787 40

We obtained pharmaco-epidemiologic data regarding the antipsychotic maintenance treatment (AMT) of schizophrenia patients through a postal survey sent to all Austrian psychiatrists and neurologists. Drug therapy was considered the most important therapeutic approach in the long-term management of schizophrenia. However, the majority of the respondents clearly were not satisfied with the current status of scientific knowledge about dosage and duration of AMT. Single-drug treatment with antipsychotics was preferred by the respondents; oral and depot neuroleptics were used with equal frequency. Haloperidol was the oral drug most frequently mentioned as first choice (44% of the respondents), followed by clozapine (14.1%) and thioridazine (9.2%). The proposed mean daily doses showed striking variations among respondents. The proposed mean length of maintenance treatment in first-episode patients was 7.3 months; in multi-episode patients, it was 20.1 months. The results show considerable variation in physicians' attitudes toward AMT.
 ...
PMID:Antipsychotic maintenance treatment of schizophrenia patients: is there a consensus? 791 Sep 77

Haloperidol levels in blood were measured in 55 acutely psychotic inpatients with schizophrenia, who were randomly assigned to three fixed doses of oral haloperidol. Nineteen of these subjects received 10 mg/day, 18 received 30 mg/day, and 18 of them received 80 mg/day. All of the subjects were treated under double-blind conditions for 6 weeks or until remission. Haloperidol and reduced haloperidol levels were measured in plasma and red blood cells at the end of 2, 4, and 6 weeks of treatment. There were statistically significant linear correlations between the dose of haloperidol and levels in blood. An examination of data for linear and curvilinear relationships between levels in blood and clinical response did not yield any statistically significant relations. The data did not support the concept of a "therapeutic window." The ratio of reduced haloperidol to haloperidol levels in plasma or red blood cells did not yield any statistically significant correlations to clinical outcome.
 ...
PMID:Blood levels of haloperidol and clinical outcome in schizophrenia. 802 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>