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Biomedical subjects

B M Cohen

Publications and source records attributed to B M Cohen.

At least 127 records · Page 7Linked to original sources
PubMed1987

Alpha 2-adrenergic receptors in platelet membranes of depressed patients: increased affinity for 3H-yohimbine.

Specific binding to alpha 2-adrenergic receptors was studied in the platelets of 31 patients with major depressive disorder and 18 normal controls using the selective antagonist 3H-yohimbine. Receptor density for depressed patients (Bmax = 88 +/- SD 45.1 fmoles/mg) was not significantly lower than that for controls (124 +/- SD 78.1 fmoles/mg). The affinity of the receptor for yohimbine was significantly greater in depressed patients (Kd = 1.05 +/- SD 0.47 nM) than in controls (Kd = 1.47 +/- SD 0.63 nM). This is consistent with the hypothesis of increased alpha 2-adrenergic receptor sensitivity in depressive disorders. Past studies of alpha 2-adrenergic receptors on platelets are reviewed, and the importance of designing studies with sufficient statistical power is discussed.

Adult↗
PubMed1987

Blood to brain distribution of neuroleptics.

Knowledge of the tissue distribution of drugs is important in interpreting other more commonly measured pharmacokinetic parameters, such as levels of drug in blood. For the neuroleptics, studies of blood to brain distribution are few and, due to technical differences between studies, the results are neither consistent within drugs nor comparable between drugs. We estimated the plasma to brain distribution of several common neuroleptics in rats using a single technique, the radioreceptor assay for neuroleptics. At doses that led to plasma levels similar to those achieved in clinical use, brain to plasma ratios ranged from 34 and 22 for fluphenazine and haloperidol, respectively, to 2.2 and 0.97 for thioridazine and mesoridazine, respectively. In general, clinical milligram potency and the favorability of distribution to brain ranked in the same order. These results may explain why such low levels of the high potency neuroleptics and such high levels of the low potency neuroleptics, greater than can be explained by relative differences between the same drugs in potency in vitro, are observed in blood both by radioreceptor and chemical assay techniques.

Animals↗
PubMed1987

Platelet membrane fluidity identifies a clinical subtype of Alzheimer's disease.

1. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup (approx. 50%) of patients with Alzheimer's disease who manifest distinct clinical features. 2. We review an integrated series of studies that explore both the clinical significance of this finding and the biological basis for the platelet membrane alteration.

Aged↗
PubMed1987

Platelet membrane fluidity in Alzheimer's disease and major depression.

Double-blind fluorescence studies of platelet membrane fluidity were conducted at 37 degrees C for 51 patients with Alzheimer-type dementia, 24 nondemented depressed patients, and 50 neurologically healthy subjects. The fluidity of the hydrocarbon region of platelet membranes from the demented group, as reflected by the steady-state anisotropy of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was significantly greater than that for the depressed and normal control subjects. Within the demented group, platelet membrane fluidity was significantly correlated with severity of dementia but not with duration of illness or age at onset. Demented patients with "increased" platelet membrane fluidity had an earlier onset, were more severely demented, and deteriorated more rapidly.

Aged↗
PubMed1987

Antidepressant-related akathisia.

Five neuroleptic-free patients exhibited syndromes that were indistinguishable from idiopathic or neuroleptic-induced akathisia in association with antidepressant administration. While antidepressant-related akathisia may be produced by any of a variety of antidepressants, the susceptibility of each individual patient to the development of this disorder may be limited to only one or a few of these agents. A considerably rarer syndrome than neuroleptic-induced akathisia, antidepressant-related akathisia appears to respond to established pharmacologic treatments for neuroleptic-induced akathisia.

Adult↗
PubMed1986

In vivo potencies of antipsychotic drugs in blocking alpha 1 noradrenergic and dopamine D2 receptors: implications for drug mechanisms of action.

In addition to being dopamine antagonists, all antipsychotic drugs are potent antagonists of alpha-1 noradrenergic receptors. Nevertheless, the contribution of alpha blockade to the clinical therapeutic effects of the antipsychotic drugs has never attracted extensive study. In particular, the relative alpha-1 noradrenergic antagonist potency of antipsychotic drugs has rarely been determined in vivo during extended treatment, although such treatment would provide a better model of clinical drug effects than the determination of potencies in in vitro systems, such as assays of competition for binding sites in tissue homogenates, as is most often done. To estimate the physiological efficacy of antipsychotic drugs as dopamine and alpha adrenergic antagonists, we treated rats for four weeks with daily IP injections of the following antipsychotic drugs: Fluphenazine, 1 mg/kg; haloperidol, 1 mg/kg; chlorpromazine, 25 mg/kg; thioridazine, 25 mg/kg; and clozapine, 25 mg/kg. Effective antagonism should lead to an increase in density of the relevant receptors. After two drug-free days, rats were sacrificed and the affinity and density of dopamine D2 and alpha-1 noradrenergic receptors were determined in striatum and brain exclusive of striatum, respectively. Alpha 1 noradrenergic receptor density but not dopamine receptor density was increased after all treatments. Thus, preliminary experiments with this in vivo model suggest that all antipsychotic drugs are effective antagonists at alpha 1 noradrenergic receptors, while not all are effective antagonists at dopamine D2 receptors.

Animals↗
PubMed1986

A cell membrane correlate of tardive dyskinesia in patients treated with phenothiazines.

Phenothiazine administration to psychiatric patients is associated with an increase in the "structural order" of platelet membranes as determined by steady-state fluorescence polarization measurements with 1,6-diphenyl-1,3,5-hexatriene (DPH), a fluorescent probe that localizes preferentially in the hydrocarbon region of cell membranes (Zubenko and Cohen 1984, 1985a, b). In this study, platelet membranes prepared from a group of psychiatric patients who developed tardive dyskinesia following chronic treatment with phenothiazines exhibited a significant elevation in DPH fluorescence polarization when compared to similar preparations from an otherwise matched group of patients who had no symptoms or history of tardive dyskinesia. The distribution of polarization values obtained for the tardive dyskinesia group displayed minimal overlap with that of an unmedicated, psychiatrically-healthy control group matched for age and gender. The fluorescence polarization of DPH-labelled platelet membranes was not significantly correlated with phenothiazine daily dose or serum cholesterol concentration in the phenothiazine-treated patient groups, or with dyskinesia severity (AIMS rating) in the tardive dyskinesia group. Patient gender and the presence of an affective disorder did not significantly correlate with DPH fluorescence polarization. The potential physiological and clinical significance of these findings is discussed.

Adolescent↗
PubMed1985

Aging and the biophysical properties of cell membranes.

Fluorescence spectroscopy was used to examine the biophysical characteristics of human platelet membranes as a function of subject age. The structural order of membrane lipid domains was determined with the use of 1,6-diphenyl-1,3,5-hexatriene (DPH), a fluorescent probe that preferentially localizes in the hydrocarbon core of synthetic and biological membranes. Over the age range of subjects examined (17 to 86 years) the structural order of platelet membranes, as reflected by the steady-state fluorescence polarization of DPH, increased substantially. The magnitude of the observed increase in membrane structural order is sufficient to affect membrane-related cell functions including platelet aggregation. A major contributor to the increase in structural order of platelet membranes may have been an increase in the concentration of cholesterol in serum and tissue with age. The changes observed here in platelet membranes may be a general phenomenon of aging, as changes of similar type and magnitude have been observed in lymphocyte membranes and brain with age in other studies.

Adolescent↗
PubMed1985

In vivo effects of psychotropic agents on the physical properties of cell membranes in the rat brain.

Marked changes in biophysical properties, including structural order, have been observed in the hydrophobic core of cell membranes exposed to phenothiazines in vitro. In this study, similar changes are reported in vivo in cell membranes from the brains of rats treated with phenothiazines at doses thought to yield tissue concentrations approximating those attained in the clinical treatment of psychiatric patients. The membrane structural order parameter was estimated ex vivo by steady-state fluorescence polarization determinations using 1,6-diphenyl 1,3,5-hexatriene (DPH), a fluorescent probe that localizes preferentially to the hydrocarbon region of cell membranes. In these preliminary studies, rats received chlorpromazine (20 mg/kg), fluphenazine (1 mg/kg), haloperidol (1 mg/kg), and imipramine (1 mg/kg) in single or multiple dose protocols. As in earlier in vitro studies, exposure to the phenothiazine antipsychotics led to an observed increase in DPH fluorescence polarization ex vivo and a presumed increase in structural order. As predicted from the in vitro experiments, the effect of chlorpromazine was greater than that of fluphenazine, probably because chlorpromazine was given at higher doses. The magnitude of the effects seen was great enough to imply that physiologically significant changes in cell membrane characteristics may be produced in patients receiving phenothiazines.

Animals↗
PubMed1985

Effects of psychotropic agents on the physical properties of platelet membranes in vitro.

Normal platelet membranes were exposed in vitro to a variety of psychotropic medications commonly used in the treatment of patients with psychiatric disorders. Changes in structural order at the hydrocarbon region of the drug-exposed membranes were determined by steady-state fluorescence polarization measurements employing the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Chlorpromazine, an aliphatic phenothiazine, produced a significant increase in DPH fluorescence polarization at concentrations from 2-200 microM. Thioridazine, a piperidine phenothiazine, and three piperazine derivatives, perphenazine, trifluoperazine, and fluphenazine, produced significant increases in this parameter at concentrations from 20-200 microM. The other agents tested, including thiothixene, lithium, antidepressants, anxiolytics, and anticonvulsants, were without effect in the concentration ranges examined. The phenothiazine-induced increase in DPH fluorescence polarization apparently depended on the structure of the phenothiazine nucleus; changes in side-chain structure appeared to modulate this effect, most likely by altering the inherent membrane solubility of the agents.

Antipsychotic Agents↗
PubMed1985

Effects of phenothiazine treatment on the physical properties of platelet membranes from psychiatric patients.

Exposure of normal platelet membranes in vitro to clinically relevant concentrations of phenothiazines has been reported to result in an increase in the structural order of the hydrocarbon region of these membranes (Zubenko and Cohen 1984b,c). In this study, the order parameters (reciprocal of fluidity) of platelet membranes prepared from psychiatric patients receiving phenothiazine antipsychotic drugs were compared to those of an otherwise matched population of psychiatric patients who were not receiving medications that significantly affect this cell membrane property in vitro (Zubenko and Cohen 1984b,c). Membrane order was determined ex vivo by steady-state fluorescence polarization measurements employing 1,6-diphenyl 1,3,5-hexatriene, a fluorescent probe that localizes preferentially in the hydrocarbon region of cell membranes. Phenothiazine administration was associated with a significant increase in platelet membrane order and most likely results from a direct action of these agents on cell membranes. The platelet membrane order parameters of phenothiazine-free patients did not differ significantly from those of a matched group of unmedicated, normal controls. Platelet membrane order was not correlated with daily phenothiazine dose or serum cholesterol concentration. Patient gender did not significantly affect platelet membrane order in any of the groups studied. The potential physiological and clinical significance of phenothiazine-induced increases in cell membrane order is discussed.

Adult↗
PubMed1985

A multicenter trial of the prophylactic effect of ketotifen, theophylline, and placebo in atopic asthma.

Three hundred seventy-four patients with asthma were entered into a year-long, double-blind, double-placebo controlled study comparing the prophylactic effect of ketotifen (229 patients), theophylline (73 patients), and placebo (72 patients). The ketotifen group was larger to allow the accumulation of additional long-term safety data. The primary measure of therapeutic effect was a decrease in concomitant medication without a significant increase in symptomatology or a decrement in pulmonary functions. A patient daily diary was used to document symptoms (cough, shortness of breath, and wheeze) and concomitant medications taken during the 2-week baseline and the subsequent 12 monthly periods. After 2 months of study-drug therapy, the ketotifen patients had a greater decrease in both concomitant medication and symptomatology than either of the other groups. This delay in the onset of therapeutic activity has been observed in other studies and is characteristic of this compound. The principal side effect observed with ketotifen is initial sedation, which was found to be self-limiting and of little concern to the patient after the first month.

Adolescent↗
PubMed1985

An empirical study of psychosis in borderline personality disorder.

To assess the nature and prevalence of psychotic symptoms in borderline personality disorder, the authors reviewed the cases of 33 patients meeting DSM-III criteria for borderline personality disorder, using both "narrow" and "broad" definitions of psychosis. Only eight patients displayed psychotic symptoms meeting the "narrow" DSM-III definition; in all of these cases, the symptoms appeared to be attributable to either severe drug abuse or major affective disorder, present simultaneously with borderline personality disorder. The remaining patients displayed only "broadly defined" psychotic symptoms or symptoms that appeared to be under voluntary control. These findings weigh against the assumption that borderline personality disorder lies "on the border" of classical psychotic disorders.

Adolescent↗