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Biomedical subjects

S W Tang

Publications and source records attributed to S W Tang.

At least 55 records · Page 3Linked to original sources
PubMed1988

Inhibition of platelet [3H]-imipramine binding by human plasma protein fractions.

Inhibition of high-affinity [3H]-imipramine binding to platelet membranes by human plasma fractions and isolated plasma proteins was investigated. Several plasma proteins were found to contribute to the observed apparent inhibition and this contribution was assessed in terms of inhibitor units. Alpha 1 acid glycoprotein, high density and low density lipoprotein, IgG and alpha 1-antitrypsin were identified as effective non-specific inhibitors. Alpha-1-acid glycoprotein was confirmed to be the most potent plasma protein inhibitor. Cohn fractions were evaluated for the presence of the postulated endocoid of [3H]-imipramine binding site.

Binding Sites↗
PubMed1988

A longitudinal study of intact platelet 3H-imipramine binding in 12 normal human subjects.

Most investigators have measured binding of 3H-imipramine to platelet membranes, but some of the preparations may have contained varying proportions of intracellular protein because of contamination with incompletely lysed platelets. Since binding to membranes has been expressed with reference to the amount of protein in the membrane preparation, it is not surprising that there are discrepancies and a wide range of reported values for platelet imipramine binding in the literature. We have now completed a 9-month study of the binding of 3H-imipramine to intact platelets obtained monthly from 12 normal subjects. Using the intact platelet assay, as described by Friedl and Propping, we found that both Bmax and Kd for 3H-imipramine binding exhibited large month-to-month variations and no consistent seasonal trend was observed. The substantial variation in both Bmax and Kd among normal subjects and among samples obtained from the same individual at different times may limit the clinical usefulness of these measurements. A single blood sample is unlikely to give reliable values for Bmax and Kd for comparison purposes.

Adult↗
PubMed1988

Decreased platelet 3H-imipramine binding in Down's syndrome.

Platelet 3H-imipramine binding in 12 subjects with Down's syndrome showed a significantly lower maximal number of binding sites (Bmax) as compared to both unrelated normal and parental controls. No difference in the affinity constant (Kd) was observed. The results support the value of the platelet 3H-imipramine binding assay in the investigation of defects in serotonin metabolism in humans.

Adolescent↗
PubMed1988

Effects of amoxapine and imipramine on evoked potentials in the Continuous Performance Test in patients with affective disorder.

Twenty patients with major depressive disorder were studied with evoked potential (EP) topographic mapping after receiving placebo, imipramine, or amoxapine for 2 days in a random-assignment, double-blind design. Patients performed the Continuous Performance Test (CPT), a visual vigilance test. The stimuli were the digits 0-9, with 0 a target to be responded to with a button press. EPs were recorded from 32 channels and were averaged separately for detected and undetected targets and for false positives and correctly identified nontargets (no button press). Twenty-one normal controls were also tested. Amoxapine enhanced N120 amplitude in midline parietal and right parietal cortex where selective attention effects have been found to be greatest in studies of normal controls. Both amoxapine and imipramine enhanced differences in P200 between target and nontarget stimuli in comparison to placebo, with amoxapine differences again being greatest over midline parietal locations. CPT performance was significantly better on amoxapine than placebo.

Adult↗
PubMed1987

Do Oriental psychiatric patients receive different dosages of psychotropic medication when compared with occidentals.

The literature suggests the possibility of different drug dosage requirements between patients of different ethnic origins. This study thereby attempted to investigate the average dosages of psychotropic medications being prescribed for Orientals versus Occidentals using a retrospective drug history review and an international opinion survey. The retrospective drug history review compared drug dosages for four commonly used psychotropic medications in well matched Oriental and Occidental populations. Data from this review showed that final/maintenance dosages of amitriptyline were significantly lower for Orientals than Occidentals. The opinion survey assessed the responses of psychiatrists in the Orient, as well as in North America, with respect to average dosages prescribed for the two populations; their beliefs in possible variability and causes underlying the variability. Data indicated that significantly lower dosages of chlorpromazine, phenelzine, diazepam, and chlordiazepoxide are being prescribed for Orientals as compared with Occidentals. Beliefs in differences were dependent upon the degree of exposure to Orientals. Suggested etiological factors underlying the variability were usually related to drug metabolism, side effects, and body weight. In both types of studies, Orientals appeared to have lower prescribed dosages than Occidentals. The lower dosages, however, appeared to be a function of the physician's experience in treating the Oriental population.

Antipsychotic Agents↗
PubMed1985

Partial characterization of solubilized platelet imipramine binding sites using a new probe, [3H]3-cyanoimipramine ([3H]Ro 11-2465).

Evidence suggests that [3H]imipramine labels the recognition site of the neuronal 5-hydroxytryptamine uptake mechanism. We are investigating the linkage between these binding sites and the carrier by biochemical characterization. [3H]Imipramine-labelled sites have been solubilized from outdated human platelets using the detergent digitonin. [3H]3-Cyanoimipramine binds persistently to these sites in the presence of Na+ at 4 degrees C. At higher temperatures, and in the absence of Na+, this ligand acts reversibly. We report the use of this pseudo-irreversible ligand in the initial molecular characterization of the recognition molecule. To confirm that this ligand occupies the [3H]imipramine-labelled sites, human platelets were prelabelled with 3-cyanoimipramine before incubating with [3H]imipramine. Only low affinity [3H]imipramine binding remained. The majority of the 3-cyanoimipramine was irreversibly bound under these conditions as shown by the use of the 3H compound. Gel permeation chromatography of [3H]3-cyanoimipramine-prelabelled platelet membranes solubilized with digitonin indicated a Stokes' radius of 6.3 nm. This is larger than values previously determined for cholate-solubilized sites. We conclude that [3H]3-cyanoimipramine will be useful for further purification and reconstitution studies.

Binding, Competitive↗
PubMed1985

Variation in human platelet 3H-imipramine binding.

Platelet 3H-imipramine binding values from 45 normal controls and 20 depressed subjects were collected over a 2-year period. During this time, wide inter-individual variations in the affinity constant (Kd) and maximal number of binding sites (Bmax) were observed in the control population; however, we failed to observe a seasonal change in platelet 3H-imipramine binding. The Kd and Bmax values of depressed subjects were not significantly different from those of controls.

Binding Sites↗
PubMed1985

Prediction of treatment response in schizophrenia: clinical use of neuroleptic blood levels.

The relationship between clinical response and plasma neuroleptic levels in schizophrenia is unclear. Apart from the inadequacy of the plasma neuroleptic assay method, resistance to neuroleptic treatment in some schizophrenics presents a serious problem in studies looking into the plasma drug level versus clinical response correlation. Previous studies have suggested a very wide range of plasma neuroleptic levels in responders. At present, plasma neuroleptic level does not predict clinical response in schizophrenics in general, but may have application in special situations such as suspected drug toxicity, neuroleptic resistance or idiosyncratic response to neuroleptic drugs.

Antipsychotic Agents↗
PubMed1984

Temperature-sensitive high affinity [3H]serotonin binding: characterization and effects of antidepressant treatment.

Characterization of temperature-sensitive [3H]serotonin (5-HT) binding sites (1 and 4 nM Kd sites) revealed complex inhibition by neuroleptics and serotonin antagonists. There was no simple correlation with affinities for S1 and S2 receptors. In vivo pretreatment (48 h before) with mianserin did not alter Bmax or Kd for the 1 nM Kd [3H]5-HT site, although [3H]ketanserin (S2) densities were decreased by 50%. This suggested that possible S2 components of [3H]5-HT binding must be negligeable, even though ketanserin competed with high affinity (IC50 = 3 nM) for a portion of the 1 nM Kd [3H]5-HT site. Low concentrations of mianserin inhibited the 1 nM Kd [3H]5-HT site in a non-competitive manner, as shown by a decrease in Bmax with no change in Kd after in vitro incubation. The complex inhibition data may therefore represent indirect interactions through another site.

Animals↗
PubMed1984

Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain.

Chronic administration of loxapine or clozapine in rats for 4 weeks or 10 weeks did not produce enhancement of striatal dopamine receptor density. However, there was a marked reduction (50-60%) of cortical serotonin receptor density associated with clozapine or loxapine administration. Acute doses of clozapine or loxapine produced the same potent effect. The possibility that these two antipsychotic drugs act via the serotonin system in the brain is proposed.

Animals↗
PubMed1984

Total and free plasma neuroleptic levels in schizophrenic patients.

Nineteen male patients, under 35 years of age, newly admitted with a diagnosis of schizophrenia, were treated with either chlorpromazine or haloperidol at a fixed dosage for 25 days. Both total and free plasma neuroleptic levels were measured using a radioreceptor assay. Clinical response was measured by the Brief Psychiatric Rating Scale (BPRS). On day 25, nonresponders (those with a decrease of less than 8 points on the BPRS) had both total and free plasma neuroleptic levels within the range observed in responders. It is therefore concluded that lack of therapeutic response is generally not due to inadequate plasma drug levels.

Adult↗
PubMed1983

Unusual acute effects of antidepressants and neuroleptics on S2-serotonergic receptors.

The antidepressants mianserin and amoxapine, and the neuroleptic loxapine caused significant decreases in the number of rat frontal cortex S2-serotonergic receptors after a single acute injection. The affinity of serotonin for this site was also decreased after acute mianserin. Daily injections of loxapine and amoxapine for 2, 7 or 28 days resulted in decreased receptor density but no change in Kd. Down-regulation of S2 sites by mianserin was not dependent on endogenous serotonin stores or occupation of the S2 recognition site since chronic PCPA or acute ketanserin preadministration did not affect the mianserin-induced decreases. The results suggest that mianserin may be acting on other sites which it does not share in common with other S2-antagonists such as ketanserin.

Amoxapine↗
PubMed1983

Temperature-sensitive reversible loss of [3H]imipramine binding sites: evidence suggesting different conformational states.

Previous studies have indicated that the tertiary tricyclic antidepressant imipramine binds with high affinity to a site related to the serotonin uptake mechanism. We have further characterized this site with regards to the effects of temperature, pH and calcium ions on both rat cerebral cortex homogenates and outdated human platelets. The binding of [3H]imipramine to these sites is maximal at 4 degrees C. When the assay temperature is increased to 23 degrees C, there is approximately a 50% decrease in the maximal number of binding sites (Bmax) with no apparent change in the affinity for the ligand. On further raising the temperature to 37 degrees C there is no further decrease in Bmax but there is an increase in the dissociation constant (KD). These temperature related changes are reversed when the assay temperature is again lowered to 4 degrees C. Decreasing the pH of the incubation mixture from 7.5 to 7 (which is the pH change also observed upon changing the temperature of the incubation mixture from 4 to 37 degrees C) decreased [3H]imipramine binding by 10-20%, an amount which does not account for the changes observed. Similarly, neither calcium nor EDTA altered these reversible changes. Irreversible loss of binding sites was observed on prolonged incubation at 23 or 37 degrees C. After 20 h preincubation at 23 or 37 degrees C, 15 or 30% of the binding respectively could not be restored by lowering the temperature to 4 degrees C. This permanent loss was enhanced by calcium and inhibited by EDTA. These results suggest that reversible conformational changes in the [3H]imipramine binding site can be observed.

Animals↗
PubMed1983

Manipulations of synaptic serotonin: discrepancy of effects on serotonin S1 and S2 sites.

The effect of repeated treatment (28 day) with D-fenfluramine, a serotonin (5HT) releaser, L-tryptophan, a 5HT precursor, or fluoxetine, a 5HT uptake inhibitor, on 3H-5HT and 3H-spiperone binding in the rat cerebral cortex was investigated. Treatment with fenfluramine and fluoxetine caused a significant decrease in the number of 3H-5HT binding sites (Bmax). Fenfluramine also decreased binding of 3H-spiperone in the cortex, but fluoxetine treatment increased this binding. Treatment with L-tryptophan produced no change in the binding of either 3H-5HT or of 3H-spiperone significantly. The data show that manipulation of synaptic 5HT concentration does not always result in parallel changes in S1 and S2 receptors. This suggests that the 5HT S1 and S2 receptors may be subject to different regulatory mechanisms.

Animals↗
PubMed1983

Temperature-sensitive conformational changes in membrane-bound and solubilized [3H]imipramine binding sites.

[3H]Imipramine binding sites are located on serotonergic nerve terminals and on blood platelets. Previous studies on our laboratories have indicated temperature-sensitive conformational changes in [3H]imipramine binding sites in hippocampal and cerebral cortex membranes. We now report that similar changes are observed in both membrane-bound and digitonin-solubilized [3H]imipramine binding sites of human blood platelets. This may indicate integrity of the solubilized binding site.

Animals↗
PubMed1983

Solubilization and assay of [3H]imipramine binding sites from human platelets.

[3H]Imipramine binding sites were characterized on outdated (72-96 h) human platelets. The binding site profile was very similar to that previously described for fresh platelets and for CNS membrane preparations. [3H]Imipramine binding sites are believed to represent the recognition site for the 5-hydroxytryptamine uptake system. In order to further investigate this molecular relationship, we solubilized [3H]imipramine binding sites using 1% digitonin and characterised them using a polyethylene glycol precipitation assay. Solubilization did not alter the pharmacological specificity or affinity of the [3H]imipramine binding site and recovery of sites was very high. It was concluded that the solubilization procedure left the binding site remarkably intact. The ready availability of platelets and the convenience of the binding assay makes this system amenable for further purification steps.

Binding Sites↗
PubMed1983

Noradrenergic and serotonergic input necessary for imipramine-induced changes in beta but not S2 receptor densities.

Chronic imipramine administration decreases the density of serotonin S2 and beta-adrenergic receptors. The mode of action is not clear but might be assumed to be a result of imipramine interacting with its high affinity binding sites on presynaptic serotonin neurons. To investigate this possibility and the role of the serotonergic and noradrenergic systems on imipramine-induced receptor down-regulations, the effects of raphe lesions and 6-hydroxydopamine lesions were examined. The theory that imipramine acts through the serotonin system to down-regulate beta-adrenergic receptors was supported by the observation that raphe lesions attenuated the imipramine-induced beta receptor denumeration. However, the effect of imipramine on the S2 site may not be a result of serotonin uptake blockade. Raphe lesions which diminish 3H-imipramine high affinity binding did not alter the imipramine-induced decrease in S2 receptor numbers. 6-Hydroxydopamine lesions prevented the reduction in beta but not S2 binding. Imipramine may exert its effect on S2 binding through a site other than the high affinity, serotonin uptake site.

Animals↗