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)

The beta-lipotrophin fragment des-tyrosine-gamma-endorphin (DT gamma E) has been reported to have antipsychotic properties. We administered the compound without other psychoactive drugs to a subpopulation of schizophrenic subjects. Male patients with chronic psychotic illness and previous long-term neuroleptic therapy were given DT gamma E at a similar dose and duration of treatment that have been reported to be effective. No improvement in psychotic symptoms occurred; plasma prolactin level, a parameter characteristically altered by neuroleptic treatment, did not change. The beneficial effects of DT gamma E in schizophrenia may be specific to a diagnostic category, may be dependent on past pharmacologic treatment, or may occur only in combination with other drugs.
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PMID:Des-tyrosine-gamma-endorphin administration in chronic schizophrenics. A preliminary report. 721 42

In order to elucidate the interplay of prolactin and dopamine in schizophrenia, base-line levels of prolactin were assayed in the cerebrospinal fluid (CSF) of chronic schizophrenic patients with or without lobotomy. Cental and cortical atrophy and significantly lowered CSF prolactin levels were found in lobotomized patients in comparison to equally neuroleptic-treated non-lobotomized patients. The mean CSF prolactin level in the female patients was significantly higher than in the male patients. This study did not support the 'dopamine hypothesis' of schizophrenia, since CSF prolactin levels did not correlate with schizophrenic symptoms. The brain atrophy blocked completely the expected elevation of CSF prolactin levels induced by neuroleptics.
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PMID:Low prolactin levels in cerebrospinal fluid: an after effect of lobotomy in chronic schizophrenia. 728 16

The authors found that plasma luteinizing hormone (LH), prolactin, and testosterone were initially normal in nine acutely psychotic males with schizophrenia or schizo-affective disorder; follicle-stimulating hormone (FSH) was normal in eight of the nine. When patients were treated with pimozide, a relatively specific dopamine receptor blocker, there were statistically significant declines in FSH and LH, although levels remained within normal limits. Prolactin rose significantly, but testosterone did not change. The observed reductions in FSH and LH concentrations are consistent with the hypotheses that dopamine and/or prolactin play a role in gonadotropin secretion. The maintenance of normal levels of gonadotropins and testosterone, however, suggests that these patients possessed relatively normal hypothalamic-pituitary-gonadal axis function before and during a course of neuroleptic treatment.
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PMID:Effects of dopamine blockade on gonadotropins and testosterone in men. 735 77

Patients who presented with acute psychoses and were treated with chlorpromazine were first divided into 2 groups with good (23) and poor (13) outcome. These outcome groups differed little in their initial clinical features and showed no difference in 2 indices of dopamine receptor blockade (extrapyramidal symptoms and plasma prolactin concentrations). The group which improved was then subdivided on the basis of evidence of dopaminergic blockade into 15 who had improved and also showed anti-dopamine effects ('responders') and 8 who had improved but showed no anti-dopamine effects ('remitters'). The remainder were eventually classified as 'resistant' to the effects of the drug. The group of 'remitters' contained no patients with nuclear schizophrenia; the 'responders' were mainly nuclear schizophrenics; and the 'resistant' patients were schizophrenic or schizo-affective. The 3 groups who were defined in this way also differed in their subsequent clinical course. It is suggested that this scheme for dividing patients may be useful in clinical work and could also assist research worker to identify the patients who can most appropriately be studied to determine mechanisms of drug action.
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PMID:Drug-related and illness-related factors in the outcome of chlorpromazine treatment: testing a model. 738 33

Akinesia, a common side effect of antipsychotic drugs, often goes unrecognized by physician and patient. Akinetic apathy and lack of spontaneity can be mistaken for the negative symptoms of schizophrenia and add to the well-known social and emotional disability of schizophrenic patients on maintenance therapy. The authors attempted to identify a measure that might distinguish between akinesia and the negative symptoms of schizophrenia but found no relationship between plasma and saliva chlorpromazine levels or prolactin levels and akinesia. The fact that all of the akinetic but only 31% of the nonakinetic patients rated themselves as drowsy 12 hours after their bedtime dose indicates that drowsiness is a fairly accurate correlate of akinesia.
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PMID:Importance of akinesia: plasma chlorpromazine and prolactin levels. 743 84

A line of evidence indicates changes of the immune system in schizophrenic patients. We investigated the production of cytokines by peripheral blood mononuclear cells (PBMCs) in drug-free and neuroleptic-treated schizophrenic patients compared to healthy, normal controls. A significant reduction in interleukin (IL)-2 production was detected in untreated schizophrenic patients (-59.6%; p < .05) as well as in IL-3-like activity (IL-3-LA) production (-27.4%; p < .05) in treated patients compared to controls. No alteration was observed in IL-1 beta production. It seems that schizophrenia is associated with diminished IL-2 production, while neuroleptic treatment interferes with the capacity of immunocompetent cells to synthesize and/or release Il-3-LA. The alteration in cytokine production did not correlate with either the severity of the disorder or the serum prolactin levels.
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PMID:Cytokine production in drug-free and neuroleptic-treated schizophrenic patients. 749 23

22 acutely schizophrenic patients with partial remission under standard haloperidol therapy (reduction in BPRS total score by 50% or less) were included in this prospective study. There was a significant correlation between the BPRS total score or the BPRS factors Anxiety/depression and Anergia and extrapyramidal side effects at the end of the 3-week neuroleptic treatment phase. In these patients abrupt discontinuation of neuroleptic medication (suspension therapy) brings about a significant further reduction in BPRS total scores together with a favorable effect on the BPRS factors Anxiety/depression, Anergia and Thought disturbance. There was a trend towards low serum prolactin values before neuroleptic discontinuation being linked with a favorable effect of subsequent suspension therapy. Urinary dopamine and homovanillic acid excretion before neuroleptic discontinuation did not predict the clinical suspension effect. Thus peripheral neuroendocrine and biochemical effects of haloperidol-induced dopamine blockade and their changes after discontinuation of neuroleptic medication seem not to be linked with the clinical effect of suspension therapy in acute schizophrenia. There was, however, a significant relationship between low urinary epinephrine, norepinephrine, vanillylmandelic acid and cortisol excretion before suspension therapy and a favorable suspension effect. On the other hand, the more pronounced a nonspecific stress constellation (catecholamines, cortisol) was in patients with an unsatisfactory remission under neuroleptics, the less favorable was the clinical effect of suspension therapy. Until now, the treatment courses of suspension therapy have been evaluated in 43 schizophrenic patients. According to both clinical aspects and observer rating, three types of therapeutic suspension effects have been distinguished in one-third of the cases respectively; none (at best temporary remission, no improvement in the overall treatment situation); partial (substantial remission, neuroleptic medication resumed for therapeutic reasons), and favorable (almost complete remission, neuroleptic medication resumed for prophylactic reasons).
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PMID:Suspension therapy in acute schizophrenia. Clinical and neuroendocrine/biochemical effects of abrupt discontinuation of neuroleptic medication. 760 62

We used the PCR amplification technique in an attempt to characterize further the dopamine D2L receptor expressed in the prolactin-secreting pituitary MMQ cell clone, derived from the prolactin- and ACTH-secreting Buffalo rat 7315 alpha pituitary tumour. By semiquantitative PCR amplification we were unable to detect the mRNA encoding the D2S receptor isoform, which derives from the well-known process of alternative splicing, producing two D2 receptor subtypes (D2L and D2S) in such tissues as the anterior pituitary and the corpus striatum. Although the pharmacology of the D2 receptor has been established in many studies on both native receptors and transfected receptor isoforms, because of the lack of tissues naturally expressing only one receptor isoform, MMQ cells represent the first example of cells uniquely or prevalently expressing only the D2L receptor, conceivably coupled to its native transduction mechanisms. These considerations prompted us to evaluate the pharmacology and the second messenger systems known to be modulated by dopamine. Scatchard analysis of [3H]spiperone binding resulted in a linear plot, consistent with the existence of a single class of binding sites, with a Kd of 0.055 +/- 0.002 nM and a Bmax of 27 +/- 3.5 fmol/mg protein. Competition experiments confirmed the GTP-dependence and the order of potency for agonist and antagonist ligands consistent with binding to a D2 receptor. The inhibitory effects of dopamine on adenylyl cyclase activity, inositol phosphate production and intracellular free calcium concentrations, the latter presumably via the opening of K+ channels, and prolactin secretion, as well as the reversal of the effect by the D2-selective antagonist (-)sulpiride and pretreatment with pertussis toxin, are consistent with the known biological actions of dopamine at D2 receptors. Based on our observations, the MMQ cell line can be considered a useful tool for investigating ligand-receptor interactions to develop new selective dopaminergic D2L ligands for the therapy of dopamine-related disorders such as schizophrenia, depression, Parkinson's disease and drug addiction.
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PMID:Absence of D2S dopamine receptor in the prolactin-secreting MMQ pituitary clone: characterization of a wild D2L receptor coupled to native transduction mechanisms. 766 27

The prolactin (PRL) response to 0.5 mg of intravenous haloperidol (HPL) IV may be a measure of tuberoinfundibular dopaminergic activity. Our earlier reports, using multidiagnostic strategies in schizophrenia, suggested that psychoses characterized by the absence of affective syndromes (Keks et al 1990) and the presence of thought disorder and passivity delusions (Keks et al 1992) are linked to blunted PRL responses. In this paper we evaluated the relationships between basal and HPL-stimulated PRL concentrations, and a number of potentially relevant symptom measures. Basal PRL was lower in patients without a depressive syndrome and suicidal ideation. Stimulated PRL was lower in patients without neurovegetative symptoms (versus patients with neurovegetative symptoms and controls), with depression (versus patients with no depression and controls) and those with disorder of associations (versus patients without association disturbance and controls). These findings can be interpreted as indicating a link between endocrine measures of dopaminergic function and a subtype of schizophrenic psychosis characterized by the presence of thinking disturbance in the absence of depression.
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PMID:Basal and haloperidol-stimulated prolactin and symptoms of nonaffective and affective psychoses in neuroleptic-free men. 771 Nov 59

There is considerable interest in the role of serotonin (5-HT) in the pathophysiology of schizophrenia and in the mechanism of action of clozapine, an atypical antipsychotic agent and a potent dopamine (DA), 5-HT2/5-HT1C and histamine (H) antagonist. Cimetidine, an H2 antagonist, produces robust, transient increase in plasma prolactin (PRL) levels in man following intravenous administration. This effect has been attributed, in part, to indirect central serotonergic mechanisms involving 5-HT2 receptors in the hypothalamus, but the evidence is inconclusive. This study investigated the effects of cimetidine on plasma PRL levels in unmedicated schizophrenic patients versus normal controls and the effect of chronic treatment with clozapine on the cimetidine-induced PRL response. The PRL response to cimetidine was significantly blunted in male but not female schizophrenic patients. The PRL response in male schizophrenic patients was inversely related to psychopathology. Chronic treatment with clozapine completely suppressed the plasma PRL response following cimetidine. These data are consistent with the hypothesis of an abnormality of serotonergic activity, including downregulation of 5-HT2 receptors, in male but not female schizophrenic patients. The role of antagonism of 5-HT2 receptors in the action of clozapine is discussed.
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PMID:The cimetidine-induced increase in prolactin secretion in schizophrenia: effect of clozapine. 783 46


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