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Biomedical subjects

S W Tang

Publications and source records attributed to S W Tang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Brain sigma receptors labelled by [3H]nemonapride.

Binding of [3H]nemonapride and [3H]raclopride was examined in the brain areas of three species (rat, cow and human). The results indicated that [3H]nemonapride binding is inhibited by selective sigma receptor ligands in frontal cortex, striatum and cerebellum. Only the striatum showed significant dopaminergic sites as defined by sulpiride. Use of the subtraction method of [3H]nemonapride minus [3H]raclopride binding as a measure of D4 dopamine receptor binding may, therefore, also include a sigma receptor component.

Animals↗
PubMed1996

Serotonin indices and impulsivity in normal volunteers.

Hormonal responses to oral paroxetine were examined in a group of healthy subjects. The calcium response to serotonin (5-hydroxytryptamine, 5HT), mediated by platelet 5HT2A, was also measured. Paroxetine elicited a cortisol response that was directly correlated with the magnitude of platelet calcium response. The cortisol response was also correlated with the trait of impulsivity. These results suggest that paroxetine may be a useful probe in studies of serotonergic systems.

Administration, Oral↗
PubMed1996

Paroxetine shifts imipramine metabolism.

The combination of selective serotonin reuptake inhibitors with tricyclic antidepressants has proven useful in treatment-resistant depression but has the potential for adverse drug-drug interactions. In the present study, the metabolism of a single dose of imipramine was studied before and after treatment with paroxetine. Paroxetine induced significant elevations of approximately 50% in half-life, area under the curve, and Cmax of imipramine and decreased clearance twofold. The effects on desipramine pharmacokinetics were even more pronounced. These findings indicate a significant interaction of paroxetine with the CYP2D6 isoenzyme.

Adult↗
PubMed1996

A pilot evaluation of the EMBU Scale in Japan and the USA.

Cultural differences in parental attitudes and child-rearing practices among European countries have been demonstrated in previous studies using a scale for assessment of memories of upbringing (the EMBU). In this pilot study we evaluated the EMBU in two previously unstudied populations: a culturally homogeneous sample from Japan (n = 105) and a culturally mixed sample from Southern California (n = 73). The results suggest that, compared to European parents, Japanese parents are more emotionally distant from their children, while the Southern Californians as a group scored similarly to the Europeans. Further studies are needed in order to establish the EMBU as a transcultural tool for assessment of parental rearing behaviour.

Adolescent↗
PubMed1995

Serotonin-stimulated intracellular calcium mobilization in platelets from alcoholic men.

Numerous lines of evidence have suggested a key role for serotonin (5-hydroxytryptamine, 5HT) pathways in the regulation of alcohol consumption. To explore the functioning of the 5HT2 receptor in alcoholism, 5HT-stimulated intracellular calcium response was measured in platelets from abstinent alcoholic patients and normal comparison subjects. No difference in resting or stimulated calcium levels was observed. This finding suggests that 5HT2 receptor function is unaffected in non-drinking alcoholic subjects. The previously reported 5HT inhibition in actively drinking alcoholic subjects is likely to be a state rather than trait marker of alcoholism.

Adult↗
PubMed1995

Tyrosine kinase inhibitors regulate serotonin uptake in platelets.

Uptake of tritiated serotonin into human platelets was found to be rapidly inhibited by the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate. Binding studies indicated that uptake inhibition did not correlate with direct binding of these inhibitors to the transporter. Chelation of mobilizable intracellular Ca2+ did not inhibit the effects of genistein on uptake. These results suggest a more direct, non-Ca2+ mediated effect of tyrosine kinase inhibitors on uptake.

Blood Platelets↗
PubMed1995

Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets.

The serotonin uptake inhibitors sertraline, paroxetine and fluoxetine were compared with imipramine and the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) and calmidazolium, for their effects on intracellular Ca2+ mobilization in human platelets. All serotonin uptake inhibitors and calmodulin antagonists augmented thrombin-mediated increases in intracellular Ca2+. Sertraline, calmidazolium and W-7 also caused large dose-dependent increases in baseline levels of intracellular Ca2+. There was a rough correlation between the ability to elevate intracellular Ca2+ and potencies for inhibition of calmodulin. Neomycin, an inhibitor of inositol trisphosphate (IP3) generation, significantly inhibited the effects of sertaline. This is consistent with a role of IP3 and calmodulin in the effects of these drugs.

1-Naphthylamine↗
PubMed1994

Kinase inhibitors compete with imipramine for binding and inhibition of serotonin transport.

Effects of kinase inhibitors and activators on the binding of tritiated imipramine and inhibition of serotonin uptake were tested in platelets. The majority of compounds inhibited specific [3H]imipramine binding and serotonin uptake with affinities similar to those reported for their action on protein kinases themselves. Many of these compounds are derivatives with modified naphthalenesulfonamide or isoquinolinesulfonamide structures, which appear to compete directly with imipramine for binding to the serotonin transporter. This is of great importance for studies involving kinase regulation since at these concentrations, the inhibitors and activators were previously thought to interact virtually exclusively with protein kinases.

Binding, Competitive↗
PubMed1994

Interaction of lectins with human platelet serotonin transporter.

Lectin affinity chromatography was used to demonstrate the glycoprotein nature of the serotonin (5-HT) transporter. The human platelet transporter protein was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), labelled with [3H]cyanoimipramine and chromatographed on lectin columns. Wheat germ, gorse seed and lentil lectin-agarose columns specifically retained 5-HT transporter. Peanut and horse gram lectins were ineffective. Concanavalin A showed high non-specific adsorption. Binding of [3H]imipramine to platelet membranes or solubilized 5-HT transporter was not affected by lectins. These data suggest that the lectin interaction with 5-HT transporter is extrinsic to the antidepressant binding site.

Binding Sites↗
PubMed1993

Further evidence for the existence of endogenous serotonin uptake inhibitors and their purification by calmodulin affinity chromatography.

Experimental evidence suggests the occurrence of endogenous antidepressant-like compounds in the brain, blood plasma, and urine. After extensive purification by calmodulin-sepharose affinity chromatography, and further purification of the urine-derived sample by exclusion chromatography, at least three distinctive fractions have been identified. These fractions effectively inhibited serotonin uptake, imipramine, and/or paroxetine binding, and they apparently contained some compounds that were recognized by the anti-imipramine or anti-paroxetine antibodies. Their identification may have significant implications for studies of affective illness.

Adult↗
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↗