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Biomedical subjects

R C Meibach

Publications and source records attributed to R C Meibach.

At least 19 recordsLinked to original sources
PubMed1995

Effect of risperidone on hostility in schizophrenia.

The objective was to examine effects of risperidone on hostility and compare these effects with those of haloperidol. On the basis of risperidone's pharmacologic profile, we hypothesized that risperidone has a selective effect on hostility and that this effect is greater than that of haloperidol. The data were obtained in a multicenter clinical trial of risperidone under placebo-controlled, double-blind conditions (duration, 9 weeks). The patients were 139 patients with the diagnosis of DSM-III-R schizophrenia. Hostility was measured by the "hostility" item of the Positive and Negative Syndrome Scale. Change in hostility served as a dependent variable in the analyses. Change in "psychosis" was applied as a covariate; it helped us examine changes in hostility that were unrelated to change in psychosis (selective effect). Risperidone had a greater selective effect on hostility than did haloperidol or placebo. This finding should encourage tests of risperidone as a treatment for patients who show frequent overt physical aggression.

Adolescent↗
PubMed1994

Risperidone in the treatment of schizophrenia.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic patients and determine its optimal dose. METHOD: This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States. Patients were randomly assigned to 8 weeks' treatment with placebo, one of four doses of risperidone (2, 6, 10, or 16 mg), or 20 mg of haloperidol daily. RESULTS: Clinical improvement (20% reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% of the patients receiving 2 mg of risperidone, 57% receiving 6 mg, 40% receiving 10 mg, and 51% receiving 16 mg; and by 30% receiving haloperidol and 22% receiving placebo. Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol. Positive symptom scores were significantly lower after 6, 10, and 16 mg of risperidone and 20 mg of haloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 16 mg of risperidone. The incidence of extra-pyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo. The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 16 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo. CONCLUSIONS: Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia.

Adolescent↗
PubMed1994

Pharmacokinetics of risperidone in chronic schizophrenic patients.

In a randomized, crossover study, 24 schizophrenic patients received a single 4-mg dose of risperidone in caplet or tablet form. Each of the two study periods lasted 5 days. Blood samples to determine (by radioimmunoassay) plasma levels of risperidone and its major metabolite, 9-hydroxy-risperidone (9-OH-risperidone), were obtained each day. The two formulations of risperidone were bioequivalent. Following are the mean pharmacokinetics of risperidone and risperidone + 9-OH-risperidone: area under the plasma concentration curve (AUC) from 0 to 96 hours; 278.0 and 716.9 ng.hr/mL; AUC from 0 to infinity, 291.9 and 762.4 ng.hr/mL; peak plasma concentration, 33.0 and 44.5 ng/mL; time to peak concentration, 1.39 and 1.78 hours; and elimination half-life, 14.93 and 23.04 hours. These results demonstrate that the active moiety (risperidone plus 9-OH-risperidone) has a half-life of 23 hours and reveal a pool of risperidone (terminal half-life, 14.9 hours) that may allow twice-daily or even once-daily dosing.

Adolescent↗
PubMed1992

Risperidone: clinical safety and efficacy in schizophrenia.

Risperidone represents a unique pharmacology of potent antagonism of both serotonin and dopamine receptors. In a randomized, parallel-group, double-blind trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in acute exacerbation, risperidone showed a quicker onset of antipsychotic activity than did haloperidol. Risperidone treatment was statistically superior to placebo, with a trend toward superiority to haloperidol. Risperidone did not differ from placebo on assessment scales of extrapyramidal side effects, but produced significantly less than did haloperidol. There were no major adverse reactions associated with risperidone use, but it was noted to reduce the signs of tardive dyskinesia. This study suggests that risperidone may offer a superior side-effect profile, and possibly greater efficacy, than a standard neuroleptic such as haloperidol.

Adult↗
PubMed1987

Comparative efficacy of propranolol, chlordiazepoxide, and placebo in the treatment of anxiety: a double-blind trial.

The efficacy and safety of propranolol in the treatment of anxiety was compared with those of chlordiazepoxide and placebo in a 3-week, double-blind study of 212 patients. After a 1-week, single-blind placebo-washout period, patients were randomized to receive either propranolol (80, 160, or 320 mg/day), chlordiazepoxide (30, 45, or 75 mg/day), or placebo. Patients were evaluated by three physician-rated scales--Hamilton Rating Scale for Anxiety (HAM-A), Covi Anxiety Scale (CAS), and Clinical Global Impressions scale--and two patient-rated scales--Symptoms Checklist 90 and Profile of Mood States. Patients in all groups demonstrated significant improvement in their level of anxiety at all time points compared with their baseline level. At Week 1 propranolol and chlordiazepoxide patients were significantly better than placebo patients, as measured by the HAM-A and CAS. At Week 2 only propranolol was superior to placebo, based on HAM-A and CAS scores. Fifteen patients prematurely terminated because of adverse reactions (4 taking propranolol, 4 taking placebo, and 7 taking chlordiazepoxide). The incidence of side effects was similar for the two active drugs; fatigue, drowsiness, and change in libido were significantly more frequent with chlordiazepoxide and drowsiness and indigestion were more frequent with propranolol compared with placebo.

Adolescent↗
PubMed1984

Regional differences in binding of [3H]LSD and [3H]5-HT in calf hippocampal slices revealed by radioautography and rapid filtration studies.

Previous radioautographic experiments demonstrated that binding sites labeled by [3H]5-HT and [3H]LSD in rat brain were seen in all layers of CA1, CA4 and the dentate gyrus but not in fields CA2 and CA3 of the hippocampus. In an attempt to confirm this observation we performed binding assays on homogenates from selected areas of calf hippocampus since the small size of the rat hippocampus precluded using preparations from this animal for this purpose. Studies on homogenates from calf hippocampal regions, were done after we determined that the binding to slices in vitro was similar in the calf and rat. Binding of both [3H]5-HT and [3H]LSD by homogenates of CA1 and dentate gyrus, but not of CA3, was saturable. These studies show that the qualitative differences in binding site distribution within the calf hippocampus seen by radioautography reflect quantitative differences in the densities of binding sites revealed by the homogenate studies.

Animals↗
PubMed1982

Sexually dimorphic cerebral asymmetries in 2-deoxy-D-glucose uptake during postnatal development of the rat: correlations with age and relative brain activity.

Using a modification of the 2-deoxy-D-glucose technique we have studied developmental changes in local cerebral glucose incorporation. The data were analyzed in terms of per cent uptake, relative brain activity and left-right asymmetry for 7 brain regions. We have shown previously that left-right asymmetries exist at birth and now report: (a) that left-right asymmetries change with age, there being both left-to-right and right-to-left maturational gradients in different structures; and (b) that in most brain regions, the more active a structure is relative to the rest of the brain, the more likely that structure is right-biased and vice-versa. Some of these relationships manifest sexual dimorphism. Collectively, these data indicate that there are dynamic relationships between brain activity, brain asymmetry and brain development in the rat.

Age Factors↗
PubMed1981

A projection from the entorhinal cortex to the nucleus accumbens in the rat.

A study was performed in which both anterograde ([3H]leucine radioautography) and retrograde (horseradish peroxidase (HRP) histochemistry) tracing methods were employed to identify the origin of the fimbrial projection to the nucleus accumbens in the rat. The data reveal that this pathway arises predominantly from layers II--III of the anterior two-thirds of entorhinal cortex rather than from any part of hippocampal formation.

Animals↗
PubMed1981

Amphetamine-induced rotation in normal cats.

Amphetamine elicited dose-related rotation (circling behavior) in 9 naive cats; all cats also rotated, at lower rates, during non-drug sessions. The direction of rotation was consistent for each cat, with 6 cats rotating to the right and 3 to the left. The results extend the generality of previous findings involving rodents and suggest that an endogenous asymmetry in striatal dopamine activity may be a common characteristic of many animal species.

Animals↗
PubMed1981

The ontogeny of hippocampal energy metabolism.

The postnatal functional development of the hippocampus has been studied with the use of the 2-deoxyglucose method. Metabolic changes occurred along three different axes with increasing age. High metabolic activity appeared first in the pyramidal cell layer and shifted to the molecular layer. Activity in the regio inferior preceded the regio superior at posterior and ventral levels. All of these changes occurred first in the dorsal hippocampus and progressed along the septal-temporal axis. The data suggest that maturational changes occur at different hippocampal regions and that critical periods in development may ultimately be specified with respect to different regions in the same structure.

Aging↗
PubMed1981

Amphetamine enhancement of reward asymmetry.

Rats with bilaterally implanted lateral hypothalamic electrodes were tested daily for self-stimulation to each side of the brain; rotation (circling behavior) was recorded concomitantly. All rats rotated in a perferred direction regardless of the side of the brain stimulated and all rats had asymmetries in self-stimulation sensitivity (threshold and rate-intensity functions) related to the direction of rotation. Amphetamine both enhanced rotation and potentiated the asymmetry in self-stimulation sensitivity. Subsequently rats were tested in a choice procedure providing concurrent access to rewarding stimulation of either side of the brain; currents were titrated such that, under baseline conditions, rats continually alternated between self-stimulating one side of the brain or the other. Amphetamine induced a robust preference for stimulation to the more sensitive side of the brain (the side having a lower threshold). The results are discussed in relation to mechanisms of drug reinforcement and to biological etiologies of schizophrenia. It is proposed that schizophrenia results from a lateralized overactivity of dopaminergic neuronal systems mediating reward and that amphetamine mimics schizophrenic symptomatology by enhancing lateralization of the same systems.

Amphetamine↗
PubMed1981

Sexually dimorphic brain and behavioral asymmetries in the neonatal rat.

The 2-deoxy-D-glucose method was used to study asymmetries in cerebral metabolic activity in neonatal rats. Left-right asymmetries in 2-deoxy-D-glucose uptake were observed in hippocampus, diencephalon, cortex, and medulla-pons: 2-deoxy-D-glucose incorporation was greater in right hippocampus, right diencephalon, left cortex, and left medulla-pons. These asymmetries occurred only in females. We also observed neonatal asymmetries in tail position that, in both sexes, were predictive of adult turning preferences; females had right-sided biases in both neonatal and adult characteristics. Collectively these data indicate that cerebral lateralization is sexually dimorphic and is present at birth.

Animals↗
PubMed1980

Localization of naloxone-sensitive [3H]dihydromorphine binding sites within the hippocampus of the rat.

In vitro radioautographic experiments were performed on coronal rat brain slices to determine the precise localization of [3H]dihydromorphine binding sites sensitive to naloxone, within the hippocampus. Binding was observed in all cell fields and in dentate gyrus (DG) in the order CA2 greater than CA1 greater than CA3 greater than DG. Within each cell field the density of receptors was greatest in the stratum pyramidale, which in field CA2 was 77% as dense as the striatum. The existence of a dense population of opiate binding sites within the hippocampus is consistent with the view that this structure is involved in opiate actions.

Animals↗