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Biomedical subjects

M Stanley

Publications and source records attributed to M Stanley.

At least 163 records · Page 9Linked to original sources

High plasma concentrations of metoclopramide are not detected by radioreceptor assay.

Plasma samples from individuals treated with equivalent doses of metoclopramide or thioridazine were tested for their potency in the radioreceptor assay. Samples of plasma from patients treated with thioridazine actively displaced 3H-spiroperidol from striatal membranes, while plasma from patients treated with metoclopramide were virtually inactive. The lack of activity in the radioreceptor assay is of particular interest as the concentration of metoclopramide determined by gas chromatography, in the same plasma samples, indicates a mean value of 1,102 ng/ml.

Animals↗

Tritiated imipramine binding sites are decreased in the frontal cortex of suicides.

Binding characteristics of tritiated imipramine were determined in the frontal cortex of suicides and well-matched controls. Maximal binding was significantly lower in brains from the suicides. This finding is consistent with reports of decreased tritiated imipramine binding in the platelets of patients diagnosed as having a major affective disorder.

Adolescent↗

Erythrocyte glycine in depressed, hypomanic, and euthymic bipolar patients treated with lithium carbonate.

Red blood cell (RBC) glycine levels were examined in 27 bipolar patients, treated with lithium carbonate for a minimum of 8 months, who were either hypomanic, depressed, or euthymic in their mood. We found no difference in the RBC glycine or in the RBC: plasma glycine ratio between the hypomanic, depressed, or euthymic patients (P less than 0.1). There were statistically significant differences in RBC glycine levels in lithium-treated euthymic patients and normal controls. There was a strong positive correlation between serum lithium levels and both RBC glycine levels and the RBC: plasma glycine ratio.

Adult↗

Clinical trials of benzamides in psychiatry.

The utility of the benzamides in clinical psychiatry requires further evaluation. Of the four compounds mentioned in this chapter, it seems clear that sulpiride is an effective antipsychotic agent as shown by double-blind trials comparing it with placebo and reference antipsychotics (see Table I). Claimed efficacy for this agent in depression, anxiety, and school-phobia require more intensive evaluation. Sultopride has been reported to have efficacy in a variety of psychiatric syndromes, i.e., manic depressive illness and agitation associated with alcoholic syndromes. Tiapride has reported efficacy in a variety of alcoholic states, agitation associated with medical disease, and movement disorders. Unfortunately, all of the studies on both tiapride and sultopride have been open trials on which the results were based solely on the global clinical impression of the investigator. The total lack of formal diagnostic criteria, adequate study design, small sample size, heterogeneity of diagnosis, and questionable length of time for treatment of these disorders make it impossible to draw any firm conclusions at this time as to the efficacy toward any psychiatric disorder. Metoclopramide, on the other hand, may not only have possible antipsychotic efficacy based on one open study (62,63) but may provide an important clue as to the action of antipsychotics in general. More double-blind studies are indicated to assess its function in acute psychosis. The four compounds do seem to have properties similar to many of the classic antipsychotic agents in view of their common dopamine-blocking activity, antiemetic, sedative, and cataleptic effects. In addition, they have similar spectrum of side effects. Certain effects such as lack of efficacy in dopamine receptor models (for metoclopramide) and questionable differences in sites of action (blocking of dopamine and mesolimbic versus nigral striatal areas for sulpiride) may indicate unique neurochemical effects for these compounds and may provide a clue to allow the investigators to better predict antipsychotic efficacy and draw inferences regarding sites of action and mechanisms underlying neuroleptic activity. The benzamides have been used extensively in France since 1967. Before these drugs can be considered to be effective antipsychotic agents on par with phenothiazines and butyrophenones, further double-blind studies are indicated. These studies would give us a better idea as to whether they fit into the psychiatrist's armanentarium and may allow further insights into the relationship between descriptive psychopathology and neuropharmacology.

Amisulpride↗

A double-blind comparison of trebenzomine and thioridazine in the treatment of schizophrenia.

Forty inpatient volunteers with diagnoses of schizophrenia were randomly assigned to treatment either with trebenzomine or thioridazine in a double-blind study of clinical antipsychotic efficacy following a 1-week placebo treatment. Psychopathology was rated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). There was a significant difference in therapeutic response to the two drugs in that psychopathology decreased significantly for the thioridazine group, but not for the trebenzomine group. Serum prolactin was elevated during treatment with thioridazine, but not with trebenzomine. Side effects were more frequently reported for the thioridazine group. These results fail to confirm previous reports of clinical antipsychotic efficacy for trebenzomine.

Adolescent↗

Central amine metabolism in Alzheimer's disease: in vivo relationship to cognitive deficit.

Levels of the amine metabolites homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) were measured in the cerebrospinal (CSF) fluid of drug-free patients with Alzheimer's disease and compared to levels in a group of controls. No significant differences were found in CSF HVA and MHPG, although the Alzheimer's group was severely demented. Platelet monoamine oxidase (MAO) enzyme kinetics were measured and did not differ between controls and Alzheimer patients. The degree of dementia did not show any significant correlation with the levels of HVA or MHPG. It was concluded that, unlike previous reports in the literature, the dementia of Alzheimer's disease was not related to changes in central catecholamine metabolism nor was it associated with increased platelet MAO activity.

Aged↗

Preliminary findings on psychiatric patients as research participants: a population at risk?

To determine whether hospitalized mentally ill patients expose themselves to research with high risks more often than hospitalized nonpsychiatric patients, the authors asked patients from both groups if they would be willing to participate in a series of hypothetical research studies. The mentally ill patients did not agree to participate in studies of either high or low risk more frequently than nonpsychiatric patients. Both groups tended to agree to low-risk/high-benefit studies more often than high-risk/low-benefit studies. Although Brief Psychiatric Rating Scale scores clearly differentiated between psychiatric and nonpsychiatric patients, psychopathology did not correlate with willingness to participate in any of the studies.

Humans↗

Mental symptoms in Huntington's disease and a possible primary aminergic neuron lesion.

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

Basal Ganglia↗

Metoclopramide: antipsychotic efficacy of a drug lacking potency in receptor models.

Metoclopramide is a substituted benzamide derivative, structurally similar to procainamide and sulpiride. In behavioral, biochemical, and neuroendocrine tests it displays classic neuroleptic dopamine (DA) antagonist properties; in contrast to other DA antagonists, it lacks potency in currently used DA receptor models. In clinical studies using low doses or dubious measures, it was considered not to be efficacious as an antipsychotic. We now find that it indeed has a clinical profile similar to known neuroleptics when used in a dose range predicted from animal models. The findings raise questions regarding the validity and universality of several predictive models, as well as hypotheses purporting to explain molecular mechanisms of action of neuroleptic agents. The drug's inactivity in receptor models suggests that an as yet unidentified DA receptor subpopulation may be important as the mediator of many DA dependent neurobiologic phenomena.

Antipsychotic Agents↗

The differential effects of morphine, oxotremorine and antipsychotic drugs on DOPAC concentrations in rat brain.

The effects of morphine and oxotremorine on concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the rat striatum and tuberculum olfactorium (TO) have been compared with the effects of the antipsychotic drugs haloperidol, chlorpromazine and clozapine. All the drugs elevated DOPAC concentrations in both brain regions. While the dose-response curves for the antipsychotic drugs were parallel, had steep slopes and similar maxima, the curves for morphine and oxotremorine were irregularly shaped but the curve for morphine in the TO had some similarity to that of the antipsychotic drugs. From these findings, it is concluded that the dose-dependent increase in striatal DOPAC effected by antipsychotic drugs can be used to differentiate them from other drugs known to elevate dopamine metabolites.

3,4-Dihydroxyphenylacetic Acid↗

Sodium valproate in schizophrenia: some biochemical correlates.

Sodium valproate given in doses of 750-3000 mg daily to eight schizophrenic patients produced a qualitatively similar increase in symptoms in five. CSF showed no significant change in gamma-amino-butyric acid or methoxy hydroxyphenyl glycol, but homovanillic acid increased non-significantly in five patients.

Adult↗