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

Amisulpride (Solian), a substituted benzamide derivative, is distinguished pharmacologically by its marked affinity for dopamine D2 receptors and its higher affinity for limbic and hippocampic as compared with striatal dopamine receptors. The originality of this molecule lies in its observed 2 opposed actions at 2 distinct dose levels. High amisulpride doses, antidopaminergic, inhibit, in animals, the hyperdopaminergic symptomatology considered equivalent to positive schizophrenia, whereas low doses, dopamine-releasing and activating, improve hypodopaminergic symptomatology of negative schizophrenia. The ratio of about 300 between activating and inhibiting doses demonstrates the clear dose-related dissociation of effects, this ratio being, furthermore, much higher than that of other neuroleptics possessing bipolar activity. In contrast to conventional neuroleptics, amisulpride possesses only weak sedative activity and practically lacks cataleptigenic effects. This twofold action has been confirmed in clinical practice by open and double-blind studies, demonstrating in each case the rapidity of action (by the end of the 1st week) and very good tolerance, notably neurological, of amisulpride. Clinical studies (5 open and 4 double-blind) in patients with psychosis and positive symptomatology, have demonstrated that high doses of amisulpride (Solian 200) are effective against overall positive symptomatology at doses of 600 to 1,200 mg/day, doses of less than 300 mg/day being ineffective or aggravating. Improvement is obtained without "damping effect", amisulpride being as effective as haloperidol in this indication with a significantly better tolerance. In patients with negative schizophrenia (4 open and 3 double-blind studies) the effective dosage of amisulpride (Solian 50) is about 150 mg/day, doses above 300 mg being ineffective or aggravating. Improvement is marked and occurs in all negative symptomatology.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Amisulpride, neuroleptic and antinegative action]. 197 55

Sulpiride is a substituted benzamide which blocks selectively D-2 receptors. The authors tested its clinical effectiveness in schizophrenia, anorexia nervosa and bulimia nervosa. In schizophrenia its action was compared with that of haloperidol. It was revealed that sulpiride is an effective drug, in particular in schizophrenia with abulic and depressive symptoms without productive symptoms and in psychoaffective psychoses. In the treatment of anorexia nervosa and bulimia nervosa its therapeutic action was not superior to that of other preparations used in these diseases.
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PMID:[Sulpiride in psychiatric practice]. 276 92

Remoxipride is a novel substituted benzamide derivative with specific dopamine-(D2)-receptor blocking properties and selective action on brain mesolimbic functions. Ten inpatients with a DSM-III diagnosis of schizophrenia were treated with the drug in a 6-week open-label study. After 1 week placebo washout, the patients were given stepwise increased doses from 20 to 100 mg t.i.d. Most patients showed a clinically significant improvement; the mean scores in the Brief Psychiatric Rating Scale decreased from 25.8 at baseline to 11.3 at endpoint. Few adverse events were recorded and the rated extrapyramidal symptoms were lower at endpoint than at baseline. No abnormalities in clinical chemistry, haematology, cardiovascular assessments or EEG recordings were seen.
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PMID:An open study of remoxipride, a benzamide derivative, in schizophrenia. 286 58

Recently many authors have hypothesized that the desinhibitory property of some neuroleptics at low doses might be related to the activation of the dopaminergic system and that, on the contrary, the overactivity of dopaminergic functions could underly the productive symptoms of some schizophrenic states. In order to test this bipolar hypothesis two independent controlled studies were set up using the same new benzamide compound (amisulpride) at different doses in the opposite forms of schizophrenia. According to the results of these studies there are evidences to sustain the assertion that amisulpride at low doses is efficient in negative symptoms of schizophrenia such as poverty of ideation, flattening of affect, inattention, asociality and that the same compound at high doses is also efficient in productive forms of schizophrenia. Whether this bipolar activity is due to the play of different kinds of receptors according to the dosage used, or is due to the dopaminergic blockade in different brain areas related to the dosage remains a problem to be solved.
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PMID:[Efficacy of low doses of atypical neuroleptics (benzamides) in defect states]. 288 May 42

Neuroleptic drugs are believed to control schizophrenia by blocking brain dopamine receptors, although most act also on a number of other neuronal systems in brain. Substituted benzamide drugs in general, are more specific for the dopamine system. Brain dopamine receptors, however, are not a single entity. They can be divided on the basis of their linkage to adenylate cyclase. Substituted benzamide drugs are selective antagonists of the adenylate cyclase independent dopamine receptor population. They may be selective antagonists of one sub-population of these adenylate cyclase independent receptors, for unlike typical neuroleptics the receptor interaction of substituted benzamide drugs with brain dopamine receptors depends upon the presence of sodium ions. The specificity of substituted benzamide drugs for brain dopamine receptors is reflected in their behavioural profile. Typical substituted benzamide drugs do not cause catalepsy and, in general, only weakly inhibit motor phenomena. This inability to act in vivo cannot be entirely explained by the poor penetration of these drugs into brain. The unique properties of the substituted benzamide drugs might explain their clinical value in the treatment of schizophrenia and in the treatment of dyskinesias.
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PMID:Multiple dopamine receptors in brain and the pharmacological action of substituted benzamide drugs. 614 87

Several topics on recent advances in clinical psychopharmacology were reviewed. In the field of antipsychotics, the first clinical trial on haloperidol decanoate in the treatment of schizophrenia was performed and the daily changes of blood concentrations of haloperidol were also observed. The relationship between the blood cell concentrations of antipsychotics and the clinical effects was investigated. The treatment of tardive dyskinesia is still difficult. The new compounds of benzamide as antipsychotics attracted attention. Concerning the antidepressants, the recent status of relationship between blood cell levels of drugs and the clinical efficacy was discussed, and the clinical study on sustained release preparation of amitriptyline compared with usual tablets was surveyed. The pharmacological and clinical features of so-called second generation antidepressants and the influences of chronic use of antidepressants on the postsynaptic receptors were discussed. On lithium therapy, clinical importance of blood cell concentrations of lithium or lithium ratio and the changes of lithium concentrations in blood cells induced by the combinations of other drugs was discussed. Recently carbamazepine became an important drug in the treatment of affective disorders. The pharmacokinetics of benzodiazepines was frequently employed as an indicator of clinical practice.
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PMID:[Recent advances in clinical psychopharmacology]. 615 5

Sultopride, a benzamide derivative, provides rapid sedation. This makes it one of the main drugs used in psychiatric emergencies. Our study includes 26 cases of psychomotor hyperactivity originating in manic-depressive psychosis of schizophrenia. The medication had no effect on wakefulness. It was always effective on agitation but not on delusion or hallucinations. Manic forms of primary delirious experiences are the best indication for sultopride. It is mainly effective on delirium as a state rather than on delirium as an idea (Wahn, Delusion) which is secondary from a pathogenetic standpoint.
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PMID:[Sultopride in acute manic psychoses (author's transl)]. 627 34

Based on recent quantitative EEG findings of increased slow activity in negative schizophrenia indicating organicity, it was hypothesized that neuroleptics decreasing delta/theta activity should be beneficial for schizophrenics with predominantly negative symptoms. Thus, a double-blind, clinical, psychometric and neurophysiological study was carried out in 40 hospitalized patients with unproductive schizophrenia (mean age: 31 years; ICD diagnoses: 295.0, 295.1 and 295.6) who were treated randomly either with the benzamide amisulpride (AMI; n = 19) or low doses of fluphenazine (FLU; n = 21). In the first 2 weeks the daily doses were 50 mg AMI or 2 mg FLU, respectively, from the third week on up to the sixth week 100 mg AMI and 4 mg FLU. Clinical evaluations, psychometry and EEG mapping were performed on day 1 (hours 0 and 4--acute effect), on day 14 (hour 0--subacute effect) and on day 42 (hours 0 and 4--chronic and superimposed effects). Three AMI patients discontinued therapy prematurely because of productive symptoms (days 14, 28 and 35), while in the FLU group 2 patients dropped out due to depressive symptoms (days 21, 28), 1 due to productive symptoms (day 35), 1 due to ineffectiveness (day 28), and 1 because of an akinetic crisis (day 6). Statistical evaluation demonstrated a significant improvement in the AMDP apathy and Andreasen SANS score in both groups with the patients remaining severely ill as rated by the CGI. FLU-treated patients needed significantly more anticholinergic medication than the AMI-treated group. Psychometric evaluation showed in regard to the noopsyche significant improvement after subacute, chronic and superimposed AMI, while FLU-treated patients showed significant improvement only after subacute treatment. AMI was significantly superior to FLU at the hours 0 and 4 of day 42. The thymopsyche improved after subacute, chronic and superimposed administration of both compounds with a significant superiority of AMI on days 14 and 42 (4 h postdrug). EEG mapping showed a decrease of delta/theta and increase of beta activity as well as an acceleration of the centroid after acute and superimposed AMI on day 42 as compared with baseline; FLU patients exhibited a decrease of delta/theta activity and an acceleration of the total centroid too, while alpha activity was augmented and beta activity tended to be reduced. Our study demonstrated that, in addition to the new benzamide AMI, FLU in low doses may also be regarded as a neuroleptic with activating properties and may be utilized in the treatment of schizophrenics with predominantly negative symptoms.
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PMID:Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine. 791 19

Since the beginning of the neuroleptics in 1952, French psychiatrists have proposed a classification of neuroleptics, taking into account the pharmacological and therapeutic differences between these drugs. They distinguished 3 different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effects on the negative symptoms. The effect of some neuroleptics on negative symptoms is recognized by the international community, which considers clozapine to be effective. In France, in most cases, the indication of clozapine is still refractory paranoid schizophrenia. The effect of this atypical neuroleptic on other types of schizophrenic patient is not well known. Remoxipride appears to be as effective in treating psychotic symptoms and to have fewer side effects than haloperidol. Remoxipride is effective for both positive and negative symptoms. Loxapine has been prescribed in France since 1980. Its pharmacological profile is close to that of clozapine: it has dopamine (D2), histamine (H1), serotonin (5-HT2) and adrenergic (alpha 1)-blocking activities. Its best indication seems to be paranoid schizophrenia, although some data suggest bipolar action. The bipolar action of some new neuroleptics is illustrated by amisulpride, a substitute benzamide derivative. The originality of this molecule lies in its two opposite actions at two distinct doses. Doses of 600-1200 mg/day are effective against positive symptoms; 50-150 mg/day improves negative symptoms. This latter effect could be mediated by activation of the dopamine system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New antipsychotics in schizophrenia: the French experience. 791 51

Epidepride is a benzamide with high affinity for central D2- and D3-dopamine receptors. The anatomical distribution of [125I]epidepride binding was examined by autoradiography, using postmortem human whole-hemisphere cryosections. The density of [125I]epidepride binding sites was high in caudate nucleus and putamen. [125I]epidepride also labeled receptors in extrastriatal region such as in the pallidum, some thalamic nuclei, the neocortex, and the substantia nigra. The neocortical binding was heterogeneously distributed. In most cortical regions, binding sites were located in superficial layers (I-II). However, in basal levels of the occipital cortex, [125I]epidepride binding was located in a deeper layer, probably corresponding to layer V. Competition studies indicated that most of the [125I]epidepride binding represented predominantly D2-dopamine receptors, in striatal as well as in extrastriatal regions. The presence of extrastriatal D2-dopamine receptor populations is of particular interest for research on schizophrenia and antipsychotic drug action.
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PMID:Autoradiographic localization of extrastriatal D2-dopamine receptors in the human brain using [125I]epidepride. 872 16


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