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Biomedical subjects

S W Tang

Publications and source records attributed to S W Tang.

At least 19 recordsLinked to original sources
PubMed1991

Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography.

Loxapine, its N-demethylated metabolite amoxapine, and their 7- and 8-hydroxy metabolites were determined simultaneously in plasma by a simple two-step extraction procedure followed by reversed-phase liquid chromatography. Baseline separation was achieved by a 5-microns Spherisorb C6 column. The mobile phase consisted of 5 mM phosphate buffer (with 14 mM orthophosphoric acid)-acetonitrile (with 105 microM nonylamine) (77:23, v/v). Assays of the steady-state plasma samples obtained from seventeen patients on loxapine showed substantial amounts of 8-hydroxy metabolites, lesser amounts of loxapine, amoxapine and 7-hydroxyloxapine and trace amounts of 7-hydroxyamoxapine. As 8-hydroxy metabolites possess only weak dopamine-D2 blocking activity, the final neuroleptic property of loxapine may be affected significantly by metabolic polymorphism.

Amoxapine↗
PubMed1991

Conversion of bromperidol to reduced bromperidol in human liver.

Bromperidol (BRP) is an analog of haloperidol, a potent butyrophenone neuroleptic. Reductive conversion of BRP carbonyl group to reduced bromperidol (RBRP) was confirmed in vitro using human liver. This NADPH-dependent reduction of BRP showed a similar inhibition pattern and Michaelis constants to haloperidol carbonyl reductase.

Alcohol Oxidoreductases↗
PubMed1990

Preparation and characterization of anti-paroxetine antibodies.

6-nitroparoxetine was synthesized and reduced to 6-aminoparoxetine. After coupling to glutaraldehyde at the 6-position and to bovine serum albumin, the resulting Schiff's base was further reduced into an amino-derivative which served as the antigen. Anti-paroxetine antibodies were raised against this antigen in rabbits and the anti-paroxetine IgG purified by Protein A affinity chromatography. The anti-paroxetine IgG demonstrated high specificity towards paroxetine and 6-nitroparoxetine without significant cross-reactivity with other commonly used antidepressant and neuroleptic drugs. These antibodies may be useful for both plasma paroxetine level assays and uptake inhibitor binding site studies.

Animals↗
PubMed1990

Anti-imipramine antibodies recognize endogenous serotonin uptake and imipramine binding inhibitors.

Calf brain and human platelet extracts purified by Bio-Gel P2 column chromatography contained substances that inhibited serotonin uptake and 3H-imipramine binding. Some of these endogenous substances were also recognized by rabbit antibodies produced against imipramine. The data suggest the possible existence of endogenous serotonin uptake modulators, which may possess a partial molecular structure similar to that identified by the antibodies.

Animals↗
PubMed1990

Coadministration of a beta-adrenergic antagonist and a tricyclic antidepressant: a pilot study.

After a 7-day washout period, 16 subjects suffering from unipolar depression were randomly assigned to either desipramine (DMI) or DMI plus propranolol treatment for 21 days. Both groups showed a significant improvement in their scores on the Hamilton Rating Scale for Depression (HRSD) after 21 days of drug treatment. However, there was no significant difference in the improvement in HRSD scores between the two groups. The results of this pilot study support the need to reevaluate the popular belief that propranolol induces or worsens depression.

Depressive Disorder↗
PubMed1990

Reduced haloperidol/haloperidol ratios in plasma: polymorphism in Japanese psychiatric patients.

We measured plasma concentrations of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), by high performance liquid chromatography (HPLC) in 45 Japanese psychiatric patients receiving HAL. Plasma levels of HAL had a highly positive correlation with daily dose per body weight. Plasma RHAL/HAL ratios had also a dose-dependent relationship, but their distribution was nonnormal and a bimodal pattern with an antimode at 0.7 was apparent by probit analysis. There were 8 subjects (18%) with high RHAL/HAL ratios (mean = 1.26, SD = 0.41) and 37 subjects (82%) with low RHAL/HAL ratios (mean = 0.42, SD = 0.13). RHAL/HAL ratios showed little intraindividual variability (+/- 10.6%), while interindividual variability was large. This may suggest that pharmacogenetic factors are involved in the metabolism of HAL and RHAL.

Adolescent↗
PubMed1989

Haloperidol reduction can be assayed in human red blood cells.

One metabolite of haloperidol present in plasma is "reduced haloperidol." This study demonstrates that human red blood cells are capable of converting haloperidol to reduced haloperidol in vitro. The reductase involved requires NADPH, as does haloperidol (ketone) reductase in human liver cytosol.

Adult↗
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↗