ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06855.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractTo evaluate the clinical potential of sulpiride for the treatment of schizophrenic patients, a double‐blind study was performed comparing fixed doses of sulpiride (800 mg daily) and chlorpromazine (400 mg daily). Twentyfive schizophrenic (RDC) patients participated in each treatment group. Antipsychotic effects were evaluated by CPRS and NOSIE ratings before and after 1, 2, 4 and 8 weeks of treatment. Interrater reliabilities for CPRS items and subscales were satisfactory.Treatment with sulpiride or chlorpromazine resulted in a significant reduction of psychotic morbidity as estimated by CPRS and global ratings. CPRS scores reflecting autism were significantly reduced in all ratings of sulpiride‐treated patients, but only after four weeks in the chlorpromazine group. Total NOSIE scores indicated improvement in both treatment groups. A significant difference in favour of sulpiride was obtained for the NOSIE subscale “retardation”.Extrapyramidal side effects occurred at a similar frequency in both treatment groups. Autonomic side effects occurred to a greater extent in chlorpromazine‐treated patients. Lactation was reported only in four sulpiride‐treated patients. Liver transaminase enzymes in serum were markedly elevated only in chlorpromazine‐treated patients.The results indicate that sulpiride has a marked antipsychotic effect which is at least not inferior to that of chlorpromazine. A better effect on autistic components of behaviour was demonstrated for sulpiride. The results indicate a higher risk of lactation but a lower risk of anticholinergic side effects and liver toxicity for treatment with sulpiride than with c

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06856.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractSixteen out of 25 hebephrenic and paranoid schizophrenic patients completed a double‐blind cross‐over study with sulpiride and haloperidol. The patient sample was relatively chronic: Median age was 35 years (range 26–53 years), median duration of illness 10 years (4–35 years), and median duration of neuroleptic treatment 5 years (1–28 years). Each patient was treated with sulpiride/haloperidol in random order for 12 weeks with a drug‐free period before each treatment phase.Mean total BPRS (Brief Psychiatric Rating Scale) score was reduced from 25 to 15 (P<0.05) during sulpiride (800–2800 mg/day, median 1600 mg/day), and from 28 to 15 (P<0.01) during haloperidol (6–18 mg/day, median 12). There were no significant differences between the groups with respect to total BPRS score, single items or symptom clusters. However, in a few, very “chronic”, disturbed, and long‐term treated patients, haloperidol appeared more beneficial than sulpiride. Autonomic side effects and parkinsonism tended to occur more frequently during haloperidol than during sulpiride, but no significant differences were found. It is concluded that sulpiride, a specific dopamine‐2 receptor blocker, has antipsychotic effect, not significantly different from haloperidol, but may produce sli

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06857.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractClinical practice and pharmacological data suggest a possible antidepressive action of sulpiride given in low dosages. To further explore the therapeutic efficacy of sulpiride 11 patients with an endogenous type of depression were studied during treatment with an oral daily dose of 150 mg sulpiride. The present data allows the conclusion that (A) low dosed sulpiride seems to act as an antidepressant in severe and milder forms of depression, (B) a clinical progress is seen earlier than is common during treatment with tricyclics and (C) a significant increase of drive is observable. However, sulpiride maintenance therapy did not prevent early relapse into depression. The preliminary nature of these clinical observations does not allow conclusions about the ultimate utility of this drug. Moreover, it remains unclear for which patients sulpiride is appropriate or perhaps superior to conventional treatment modalities of depression.

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06858.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractSchizophrenic patients were treated with fixed doses of sulpiride (800 mg) or chlorpromazine (400 mg) during eight weeks using a double‐blind design. In order to examine relationships between pharmacokinetic, clinical and biochemical parameters in relation to treatment the following variables were recorded before and 1, 2, 4 and 8 weeks after treatment. Concentrations of sulpiride, CPZ, 7‐OH‐CPZ, nor1‐CPZ were determined in serum and CSF using liquid chromatography and mass fragmentography. Clinical variables were psychotic morbidity and side effects as evaluated by CPRS, NOSIE and side effect ratings. Monoaminergic variables were concentrations of the major cerebral monoamine metabolites, HVA, 5‐HIAA and MOPEG in the cerebrospinal fluid as measured by mass fragmentography. Prolactin levels in serum and CSF were measured by radioimmunoassay.During steady state, concentrations of sulpiride in serum varied fourfold between patients and CPZ twentyfold. Drug concentrations in serum and CSF were highly correlated in CPZ‐ but not in sulpiride‐treated patients. Although sulpiride passed into the CSF, transport between serum and CSF was restricted. In the sulpiride group, improvement of psychotic morbidity and HVA elevation in CSF tended to be negatively related to the drug concentrations in serum. Sulpiride‐treated patients with extrapyramidal side effects had significantly higher drug concentrations in serum.In CPZ‐treated patients, improvement of psychotic morbidity, HVA elevation and prolactin elevation all tended to be positively correlated to drug concentrations in serum and CSF. CPZ‐treated patients with extrapyramidal side effects also had significantly higher CPZ concentrations in serum.In both treatment groups, the MOPEG reduction in CSF tended to be correlated to improvement of psychotic morbidity.The study supplied clinical evidence for the view that antipsychotic drugs belonging to the phenothiazine and benzamide series induce antipsychotic effects in schizophrenic patients in a graded fashion which is proportional to the degree of interaction with the central dopaminergic mechanisms. The results also support the view that sulpiride has a more selective effect on central dopaminergic mechanisms than chlorpromazine.In the schizophrenic patients studied and with the doses used, sulpiride concentrations tended to be maximal with regard to clinical and biochemical effects. For CPZ on the other hand, drug concentrations in some patients seemed to be too low to induce opti

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06859.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractSchizophrenic patients were treated with the dopamine (DA)‐2 receptor blocking drug sulpiride (800 mg daily) or the non‐selective DA receptor blocking compound chlorpromazine (400 mg daily). Samples of lumbar cerebrospinal fluid (CSF) and blood were drawn before and after 1, 2, 4 and 8 weeks of treatment. Concentrations of the monoamine metabolites HVA, MOPEG and 5‐HIAA in CSF and of prolactin (PRL) in CSF and serum were determined.In both treatment groups there were significant and similar elevations of HVA concentrations. HVA levels reached peaks after 1 to 2 weeks treatment and subsequently declined almost to the pretreatment level after 8 weeks. CSF and serum levels of PRL reached maximal levels within 2 weeks and remained stable at that level in both treatment groups. There were significantly higher PRL levels in sulpiride‐ than in chlorpromazine‐treated patients, Women had higher PRL elevations in CSF in both treatment groups. The HVA/PRL ratio in CSF was significantly reduced in the sulpiride but not in the chlorpromazine group. After 1 week there was a significantly elevated 5‐HIAA level in the chlorpromazine but not in the sulpiride group. In both groups, the MOPEG concentrations were significantly reduced in relation to pretreatment levels. The reduction was significantly more pronounced in the chlorpromazine group.The results indicate that sulpiride affects central DA metabolism in a similar way as chlorpromazine when administered in doses that induce antipsychotic effects. After both drugs evidence was obtained for the development of tolerance to the effect on the receptors that regulate HVA levels in the CSF but not to receptors regulating PRL release. The different effects of the drugs on PRL, 5‐HIAA and MOPEG levels indicate that sulpiride has a more specific effect than chlorpromazine on dopaminerg

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06860.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractThe pathogenesis of tardive dyskinesia (TD) appears to consist of a combination of a predisposing vulnerability of the patient and an antidopaminergic (neuroleptic) treatment. This combination may result in 1) a relative dopamine hyperreactivity associated with an increased number of dopamine receptors and/or a cholinergic hypo‐function (reversible TD), and 2) in long‐term treatment, degenerative phenomena leading to a decreased threshold for expressing dyskinetic symptoms (irreversible TD).Sulpiride, a selective D‐2 dopamine receptor blocker, is able to suppress TD without producing a reciprocal aggravation in parkinsonism, although in vulnerable patients it may induce/aggravate parkinsonian symptoms. Animal data suggest that sulpiride has less TD‐inducing effect than traditional neuroleptics, but long‐term clinical studies are still needed to prove this suggestio

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06861.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractFive Cebus apella monkeys with persistent neuroleptic‐induced dyskinesia were given a single dose of sulpiride (20 mg/kg i.m.). The dyskinesia was reduced in all five although four developed attacks of acute dystonia which had to be reversed by anticholinergic medication in three animals. In one monkey the administration of classic neuroleptics had earlier been shown to induce a typical sequence of events. First there was a similar reduction of dyskinesia as seen in the other monkeys, 1–2 days later there was noticed a rebound deterioration lasting for several days. Metoclopramide 0.5 mg/kg, caused such a rebound effect (for 2 days), whereas sulpiride did

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06862.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractNeuroleptic 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 actin vivocannot 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 dyskinesia

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06863.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effects of classical neuroleptic drugs (haloperidol, chlorpromazine) and atypical neuroleptics, i.e. substituted benzamides (L‐sulpiride, tiapride, FLA 731(‐)) on specificin vivobinding of the dopamine antagonist3H‐spiperone and the dopamine agonist3H‐n‐propylnorapomorphine (3H‐NPA) was examined in male rats. The atypical neuroleptics were found to be considerably more potent in displacing nigral than striatal3H‐spiperone binding while the classical neuroleptics were about equipotent in the two brain regions. The benzamides also produced considerably less displacement of3H‐spiperone in the striatum than did classical neuroleptics. Furthermore, while the classical neuroleptic drugs block the striatal3H‐spiperone and3H‐NPA binding sites to about the same degree, the substituted benzamides appear to have a higher affinity for the DA receptors labelled by3H‐NPA than those labelled by3H‐spiperone. The behavioural effects of the benzamides were found to differ from classical neuroleptic drugs particularly with regard to induction of catalepsy. Thus, the induction of cataleptic behaviour was found to correlate with displacement of3H‐spiperone in the striatum while blockade of apomorphine induced hyperactivity correlated with the displacement of spipero

ISSN:0001-690X    

DOI:10.1111/j.1600-0447.1984.tb06864.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY