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Biomedical subjects

G S Zubenko

Publications and source records attributed to G S Zubenko.

At least 109 records · Page 6Linked to original sources
PubMed1985

Captopril and teprotide as discriminators of angiotensin-converting enzyme activity in brain tissue.

Titrations of angiotensin-converting enzyme (ACE; E.C. 3.4.15.1) present in human serum, as well as in homogenates prepared from post-mortem human caudate or mouse (C57BL1/6J) whole brain tissue, were performed with the selective ACE inhibitors, captopril (SQ 14225) and teprotide (SQ 20881). ACE activity present in human serum was more sensitive to inhibition by either inhibitor than the activity present in the brain homogenates. The inhibition curves for the titration of the human serum activity by both inhibitors were sigmoidal while the inhibition curves for the ACE activity present in the brain homogenates were more complex. These results suggest that the brain homogenates contained: at least two species of enzyme activity with properties similar to ACE but with differing affinities for the inhibitors, or substances without ACE activity that are capable of competing with ACE for the binding of the inhibitors. Therefore, measurements of captopril or teprotide-sensitive peptidase activity as well as inhibitor-binding activity may not always reflect ACE concentrations in brain tissue.

Animals↗
PubMed1985

Cerebrospinal fluid levels of angiotensin-converting enzyme in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy.

Angiotensin-converting enzyme (ACE, E.C. 3.4.15.1) has been identified as a normal constituent of human cerebrospinal fluid (CSF). ACE activity in CSF from adult subjects without known neurologic disorder correlated positively (P = 0.002) with age between 50 and 90 years. Patients with moderate degrees of senile dementia of the Alzheimer's type and comparably demented patients with Parkinson's disease or progressive supranuclear palsy exhibited mean levels of ACE activity that were decreased 41, 27 and 53% respectively, compared to the mean level in an age and sex-matched group of neurologically intact individuals. These results raise the possibility that ACE activity in CSF may be an index of neuronal dysfunction in certain central neurodegenerative disorders.

Aged↗
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↗
PubMed1984

In vitro effects of psychotropic agents on the microviscosity of platelet membranes.

Normal platelet membranes were exposed in vitro to a variety of psychotropic agents, including chlorpromazine, fluphenazine, haloperidol, imipramine, and lithium. Changes in microviscosity of the hydrocarbon layer 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). Concentrations of the phenothiazines chlorpromazine and fluphenazine above 200 nM produced significant increases in microviscosity, while haloperidol produced a small but consistent decrease in microviscosity in the concentration range of 200 nM to 200 microM. Imipramine and lithium were without effect. The phenothiazine-induced increase in microviscosity was apparently dependent upon the structure of the phenothiazine nucleus; side chain structure was less important to this effect.

Blood Platelets↗
PubMed1984

Use of clonidine in treating neuroleptic-induced akathisia.

Six patients with akathisia were treated with clonidine in an open, on-drug/off-drug trial. All six patients demonstrated substantial improvement of their akathisia, with four of the six obtaining complete remission. The dose of clonidine used to treat the remaining two patients was limited by the development of symptomatic hypotension. Daily doses ranged from 0.2 to 0.8 mg, and maximal response to a particular dose occurred within 24 to 48 hours. Although no effects on lithium tremor, parkinsonism, or tardive dyskinesia were observed, two bipolar patients exhibited considerable improvement in their manic and psychotic symptoms during treatment with clonidine.

Adolescent↗
PubMed1984

Comparison of metoprolol and propranolol in the treatment of akathisia.

Metoprolol was compared to propranolol in the treatment of neuroleptic-induced akathisia by means of an on-drug/off-drug crossover study. Both beta-blockers were effective, but the usefulness of metoprolol was limited by side effects due to the high dose of this medication required to produce a therapeutic effect. The mechanism of action of beta-blockers in the treatment of akathisia is discussed in light of the different pharmacologic properties of metoprolol and propranolol. The study results suggest that these agents are effective in reducing akathisia through a central mechanism of action requiring beta-2 blockade.

Adolescent↗
PubMed1984

Mood-elevating effect of captopril in depressed patients.

The use of captopril, an inhibitor of angiotensin-converting enzyme and enkephalinase, was associated with substantial mood elevation in three depressed patients. Substances that may alter neuropeptide synthesis or degradation warrant further investigation as therapeutic agents in certain neuropsychiatric disorders.

Adult↗
PubMed1984

Clonidine in the treatment of mania and mixed bipolar disorder.

The symptoms of three bipolar patients remitted after clonidine treatment. One patient presented with mixed bipolar disorder, two were manic, and all were psychotic. One patient's akathisia also appeared to respond to clonidine. Clonidine's thymoleptic effect paralleled resulting cardiovascular changes.

Adolescent↗
PubMed1984

Propranolol in the treatment of neuroleptic-induced akathisia.

Fourteen patients with neuroleptic-induced akathisia were treated with propranolol in an open trial. All patients demonstrated substantial improvement of their akathisia; nine of the 14 obtained complete remission. Response was quite rapid, occurring within 24 hours in most cases. Doses required for improvement were low (30-80 mg/day), and side effects were few. Lithium-induced tremor improved considerably, but symptoms of parkinsonism and tardive dyskinesia showed little change. Preliminary results with certain other beta blockers suggest that they are less effective than propranolol in the treatment of akathisia.

Adolescent↗
PubMed1984

Development of tolerance to the therapeutic effect of amantadine on akathisia.

Four patients with akathisia as a result of neuroleptic administration were treated with amantadine. Although substantial improvement occurred initially, all four patients developed tolerance to this therapeutic effect within 1 week. An increase in dosage also had only a transient effect. The rapid development of tolerance significantly limits the usefulness of amantadine in the treatment of akathisia. One patient who suffered from akathisia and drug-induced parkinsonism experienced significant attenuation of both movement disorders in response to treatment with amantadine. Although she became tolerant to the effect of amantadine on her akathisia within the first week of treatment, her parkinsonism did not recur. The possibility that these two neuroleptic-induced extrapyramidal syndromes are pharmacologically separable is discussed.

Adult↗