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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.
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PMID:Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine. 1 74

The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies.
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PMID:Prolactin responses to neuroleptics in normal and schizophrenic subjects. 2 87

The antipsychotic drugs have provided effective and relatively safe treatment of schizophrenia, paranoid illnesses, and manic-depressive conditions marked by psychotic features. These agents are sometimes called "neuroleptic," as virtually all produce signs of extrapyramidal neurologic disorders in addition to their antipsychotic actions; in part, evidently, the neuroleptic effects are an artifact of the means of screening of potential new agents. These agents have a strong and selective antagonistic action on synaptic mechanisms in the brain mediated by dopamine as a neurotransmitter. This antidopamine action almost certainly contributes importantly to their parkinsonism effect (basal ganglia) and their prolactin-elevating (hypothalamic) effect; in addition, antipsychotic actions may be mediated by antidopamine effects, possibly in limbic and other forebrain centers.
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PMID:The "neuroleptic" antipsychotic drugs. 1. Mechanisms of action. 3 41

The effects of the antipsychotic/antidepressant drug CI-686 on apomorphine- and amphetamine-induced stereotypies, dopamine metabolism, neuroleptic binding, and serum prolactin levels were determined. CI-686 displayed profiles of activity in each of these systems that differs markedly from those of other antipsychotics. CI-686's unique preclinical profile suggests a mechanism of action other than dopamine antagonism which could have implications regarding current thinking on the pathophysiology of schizophrenia.
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PMID:Atypical antidopaminergic properties of CI-686: a potential antipsychotic agent. 4 73

Evidence that schizophrenia may be a prostaglandin deficiency disease comes from three main sources: (1) all effective antischizophrenic drugs stimulate prolactin secretion and prolactin is a potent stimulator of prostaglandin synthesis; (2) schizophrenics are resistant to pain and inflammation and are free of rheumatoid arthritis and there is increasing evidence that prostaglandins play important roles in pain, inflammation, and rheumatoid arthritis; (3) high doses of drugs recently shown to be prostaglandin antagonists cause schizophrenia-like syndromes. The hypothesis is not necessarily inconsistent with current transmitter theories of schizophrenia since prostaglandins modify transmitter secretion and action. It does indicate radically new approaches to investigation, treatment, and drug design not suggested by the transmitter concepts.
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PMID:Schizophrenia as a prostaglandin deficiency disease. 6 91

Recent reports have suggested that high doses of propranolol may be an effective treatment in schizophrenia. To determine whether such treatment has effects on cerebrospinal fluid (CSF) amine metabolites and prolactin similar to the effects of the neuroleptic drugs, we studied CSF from ten patients before and after propanolol therapy. The initial CSF sample was removed after a drug-free period and propranolol dosage was then increased over 1 week to 1000 mg daily in all ten patients. A second CSF sample was removed after 3 weeks of propranolol therapy. Propranolol levels and prolactin in CSF were measured by radioimmunoassay. Homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were measured by gas chromatography-mass spectrometry. Propranolol had no effect on the prolactin or amine metabolite concentrations. CSF propranolol levels averaged 40 ng/ml (range less than 1--78).
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PMID:The effect of propranolol treatment in shizophrenia on CSF amine metabolites and prolactin. 11 17

Apomorphine, a direct-acting dopamine agonist, stimulates release of growth hormone (hGH) and suppresses release of prolactin (PRL) from the anterior pituitary. Previous studies comparing the magnitude of these responses in schizophrenics and controls suggest that many acute (and some chronic) schizophrenics have exaggerated hGH responses; many chronic schizophrenics (and patients with tardive dyskinesia) have blunted hGH responses to apomorphine, and possibly blunted PRL responses. The present studies extend and confirm these findings in chronic schizophrenics; in addition, several studies were undertaken to further characterize these apomorphine-induced endocrine responses. Studies in which apomorphine was given on 2 or 3 separate occasions to each of five subjects indicate that the hGH response is a highly reproducible individual index, but PRL suppression is a less satisfactory measure. hGH responses to apomorphine were consistently antagonized by pretreatment with haloperidol, supporting the concept that the hGH-releasing effect of apomorphine is mediated by its action on dopamine receptors. Cyproheptadine pretreatment was associated with erratic increases or decreases in the hGH response to apomorphine, but did not alter PRL levels or apomorphine-induced PRL suppression. The relationship of these findings to biological hypotheses of schizophrenia and to neuroleptic-induced receptor changes is discussed.
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PMID:Neuroendocrine effects of apomorphine: characterization of response patterns and application to schizophrenia research. 54 Feb 9

The author presents a hypothesis relating prostaglandin E1 (PGE1) deficiency to schizophrenia. The hypothesis is consistent with the importance of prolactin-stimulating properties in currently used antipsychotic drugs, the effect of prolactin on PGE1 synthesis, and the deficiency of PGE1 regulation in schizophrenic platelets. The author relates the PGE1 deficiency hypothesis to theories implicating dopamine and endorphins in the etiology of schizophrenia. A clinical trial in chronic schizophrenics has suggested the possible therapeutic efficacy of penicillin, a drug without dopamine-blocking actions which can stimulate PGE1 synthesis directly.
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PMID:Dopamine supersensitivity, endorphin excess, and prostaglandin E1 deficiency: three aspects of the same schizophrenic elephant. 73 62

Prolactin, FSH, LH and TSH were determined in repeated samples of serum from 16 unmedicated male patients with chronic schizophrenia. Changes in the mental states between the 2 occasions were related to changes in hormone levels. Significant inverse correlations were established between prolactin and incoherence of speech, between prolactin and total positive symptoms and between FSH and poverty of speech. A significant positive correlation was established between FSH and delusions. These findings are discussed in the context of evidence concerning the role of monoamines in the control of anterior pituitary function, and of the dopamine and other monoamine hypotheses of schizophrenia. Although prolactin secretion was not as low, as would be predicted on the basis of the dopamine overactivity hypothesis of schizophrenia, the relationship between symptom change and change in prolactin secretion was consistent with the hypothesis that increasing symptom severity is associated with increasing dopamine release from the tubero-infundibular system.
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PMID:Anterior pituitary hormone secretion in chronic schizophrenia--an approach to neurohumoral mechanisms. 87 85

One of the leading current theories of the etiology of schizophrenia is excessive activity of some brain dopaminergic tracts. One of the major objections to the theory is that thioridazine is clinically as effective a treatment of schizophrenia as other neuroleptic drugs but appears to have much less dopamine-blocking properties than these agents in man and laboratory animals. Serum prolactin levels are increased by dopamine receptor-blocking drugs. We have found that thioridazine is as effective as chlorpromazine, trifluperazine, and prolixin enanthate in increasing serum prolactin levels in unmediated schizophrenic patients, indicating it is an effective dopamine-blocking agent.
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PMID:Dopamine antagonism by thioridazine in schizophrenia. 112 Jan 75


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