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Biomedical subjects

W Z Potter

Publications and source records attributed to W Z Potter.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pharmacologic profile of natural products used to treat psychotic illnesses.

Natural products have a long history of being the sources for therapeutic drugs in medicine. Investigations of natural products also have the potential for enhancing our understanding about the pathophysiology and treatment of various disorders. The screening assays described here were conducted on the phytochemical and pharmacological profiles of natural products used to treat psychotic illnesses in Korean traditional medicine, which are eligibly archived in Tongeuibogam, a traditional medicinal book in Korea. Two rounds of radioligand receptor binding assays on natural products demonstrated that many plants show potent selectivity to various receptors, especially monoamine receptors presumed to be involved in mental disorders. Further studies for the pharmacologic activity of active ingredients and in vivo behavioral profiles focusing on the central nervous system (CNS) effects are currently under way with these plant extracts. These investigations may lead to the development of new psychotropic drugs with no serious side effects, a major concern for modern psychopharmacology.

Animals↗
PubMed1994

Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.

BACKGROUND: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine. RESULTS: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.

Adolescent↗
PubMed1994

Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder.

Cerebrospinal fluid (CSF), plasma, and urinary monoamine metabolites were determined for 29 boys, aged 6-12, with attention-deficit hyperactivity disorder (ADHD). Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolites of serotonin, dopamine, and norepinephrine, respectively, correlated significantly with behavioral measures of aggression and impulsivity/hyperactivity. However, these correlations were in the unexpected direction; for example, CSF 5-HIAA correlated positively with the Brown-Goodwin Lifetime History of Aggression Scale. HVA in CSF was positively correlated with several measures of hyperactivity. The replicability of these findings, as well as possible socioenvironmental effects, and the predictive value of CSF monoamines in prepubertal hyperactivity are the subjects of ongoing study.

Aggression↗
PubMed1994

A pharmacodynamic study of the alpha 2-adrenergic receptor antagonist ethoxyidazoxan in healthy volunteers.

Ethoxyidazoxan, a potent and highly selective alpha 2-adrenergic receptor antagonist, was administered intravenously to six healthy male volunteers in a double-blind, placebo-controlled, dose-rising design. Doses of 6 micrograms/kg and 8 micrograms/kg infused intravenously over 30 minutes produced significant elevations of plasma norepinephrine and body temperature and inhibited norepinephrine-induced platelet aggregation. Central activity was shown by reversal of the slowing of saccadic eye movements and an increase in saccade peak velocity at the higher dose. Modest increases in blood pressure were produced without change in heart rate. Ethoxyidazoxan was well tolerated, with slight changes in subjective alertness and sedation.

Adrenergic alpha-Antagonists↗
PubMed1994

In vivo evidence that nonneuronal beta-adrenoceptors as well as dopamine receptors contribute to cyclic AMP efflux in rat striatum.

We applied in vivo microdialysis to assess the effects of dopaminergic and beta-adrenergic receptor stimulation on cyclic AMP efflux in rat striatum under chloral hydrate anesthesia. Dopamine (up to 1 mM) infused for 20 min through the probe did not increase cyclic AMP, whereas both the selective dopamine D1 agonist SKF 38393 and D2 antagonist sulpiride produced modest increases. It is interesting that the beta-adrenoceptor agonist isoproterenol produced a marked increase (204.7% of basal level at 1 mM) which was antagonized by the beta-adrenoceptor antagonist propranolol. Pretreatment with a glial selective metabolic inhibitor, fluorocitrate (1 mM), by a 5-h infusion through the probe attenuated basal cyclic AMP efflux by 30.3% and significantly blocked the response to isoproterenol. By contrast, striatal injection of a neurotoxin, kainic acid (2.5 micrograms), 2 days before the dialysis experiment did not affect basal cyclic AMP or the response to isoproterenol, but blocked the response to SKF 38393. These data demonstrate the beta-adrenoceptors as well as dopamine receptors contribute to cyclic AMP efflux in rat striatum in vivo. They also suggest that basal and beta-adrenoceptor-stimulated cyclic AMP efflux are substantially dependent on intact glial cells.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro.

Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. In view of the increasing evidence demonstrating effects of the first-line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6-7 days) of rat C6 glioma cells to "therapeutic" concentrations (0.6 mM) of VPA resulted in decreased PKC activity in both membrane and cytosolic fractions and increased the cytosol/membrane ratio of PKC activity. Western blot analysis revealed isozyme-selective decreases in the levels of PKC alpha and epsilon (but not delta or zeta) in both the membrane and cytosolic fractions after chronic VPA exposure; VPA added to reaction mixtures did not alter PKC activity or 3H-phorbol ester binding. Together, these data suggest that chronic VPA indirectly lowers the levels of specific isozymes of PKC in C6 cells. Given the pivotal role of PKC in regulating neuronal signal transduction and modulating intracellular cross-talk between neurotransmitter systems, the specific decreases in PKC alpha and epsilon may play a role in the antimanic effects of VPA.

Animals↗
PubMed1994

Comparative tolerability profiles of the newer versus older antidepressants.

Although the standard tricyclic antidepressants (TCAs) are generally effective in the treatment of depression, they can cause several troublesome adverse effects. Chief among these are their anticholinergic actions, which range from annoying dryness of the mouth and constipation to potentially dangerous urinary retention and confusion or delirium in the ill and elderly. Cardiovascular effects of TCAs include orthostatic hypotension, tachycardia and cardiac conduction slowing. Many TCAs are sedating and promote weight gain. Also problematic is the potential lethality of TCAs in overdose. The continual introduction of a host of new antidepressants over the past 15 years has provided an opportunity to improve the benefit-risk ratio for many patients by reducing medication-related toxicity. Selective serotonin reuptake inhibitors (SSRIs) and amfebutamone (bupropion), among others, are examples of effective antidepressants free of tricyclic-like anticholinergic, cardiovascular, sedating and appetite/weight-increasing effects. However, the new-generation drugs also present adverse effects of their own, including gastrointestinal distress, agitation and drug-drug interactions in the case of the SSRIs, and the risk of seizures or psychosis in amfebutamone recipients. Monoamine oxidase (MAO) inhibitors have also been refined; reversible inhibitors of MAO-type A afford protection against the usually feared hypertensive reaction to indirect sympathomimetic substances. The availability of new-generation antidepressants thus increases the likelihood of clinical response with a reduction in unwanted toxicity.

Antidepressive Agents↗
PubMed1994

Catecholamines in depression: an update.

Despite extensive research, the biochemical abnormalities underlying the predisposition to and the pathogenesis of affective disorders remain to be clearly established. Efforts to study norepinephrine (NE) output and function have utilized biochemical assays, neuroendocrine challenge strategies, and measures of peripheral blood cell receptors; the cumulative database points to a dysregulation of the noradrenergic system. Depressed patients (in particular, melancholic, unipolar subjects) excrete disproportionately greater amounts of NE and its major extraneuronal metabolite, normetanephrine, than do controls. Depressed patients also show subsensitive neuroendocrine (growth hormone) and biochemical (inhibition of adenylate cyclase) responses to alpha 2-adrenergic agonists, suggesting that subsensitivity of nerve terminal alpha 2 autoreceptors may underlie the exaggerated plasma NE observed in response to various challenges in affective disorders. Future advances in brain imaging techniques and in the molecular biology of adrenergic receptor-coupled signal transduction systems offer promise for meaningful advances in our understanding of the pathophysiology of affective disorders.

Affective Disorders, Psychotic↗
PubMed1993

Effects of chronic lithium treatment on platelet PKC isozymes in Alzheimer's and elderly control subjects.

Patients with Alzheimer's disease (AD) have been reported to have abnormalities in peripheral cells similar to some of those found in the brain, including decreased levels of protein kinase C (PKC) in fibroblasts. Since increasing evidence suggests that lithium affects PKC function, we investigated the effects of 3 weeks of lithium administration on the immunolabeling of 4 PKC isozymes (alpha, beta, epsilon, and zeta) in particulate and soluble fractions from platelets of 7 patients with probable AD and 6 age-matched controls. AD patients had significantly less particulate or membrane-associated PKC zeta than normals during the placebo phase (P < 0.003). After 3 weeks of lithium treatment, AD patients had significantly less membrane-associated PKC alpha (P < 0.002), epsilon (P < 0.003), and zeta (P < 0.001) than normals. This is the first report of a difference in PKC in blood cells between AD and control subjects. These findings appear to indicate that some PKC isozymes may be differentially regulated in AD versus elderly controls, at least as evidenced in this peripheral cellular system.

Aged↗
PubMed1993

Monoamine neurotransmitter interactions in drug-free and neuroleptic-treated schizophrenics.

OBJECTIVE: To study recent suggestions by a number of investigators that interactions between monoamine neurotransmitter systems play an important role in schizophrenia. It has not been clear how hypotheses about interactions might be tested in clinical data. One means for indexing interactions between monoamine neurotransmitter systems may be to compare correlations between cerebrospinal fluid (CSF) monoamine metabolite (homovanillic acid [HVA], 5-hydroxyindoleacetic acid [5-HIAA], and 3-methoxy-4-hydroxyphenylglycol [MHPG]) or ratios of these metabolites (HVA/5-HIAA and HVA/MHPG). DESIGN: We compared these putative measures of monoamine neurotransmitter interaction in 50 drug-free patients with schizophrenia (hospitalized on an inpatient ward of a tertiary care hospital) and 33 normal controls and examined the effects of neuroleptic antipsychotic treatment on these measures in 41 patients (22 of whom had antecedent drug-free CSF data). RESULTS: Drug-free patients with schizophrenia had significantly smaller correlations between CSF monoamine metabolites than normal controls. Longer drug-free time was associated with even smaller correlations between metabolites, suggesting that the difference between controls and patients was not due to acute drug withdrawal. After treatment with neuroleptic antipsychotics there were significant increases in the HVA/5-HIAA and HVA/MHPG ratios, as well as increases in correlations between monoamine metabolites. After treatment, there were no significant differences in metabolite correlations between patients and controls. Metabolite ratios and correlations did not predict subsequent treatment response, but preliminary analyses demonstrated negative relationships between HVA/5-HIAA and HVA/MHPG ratios and Brief Psychiatric Rating Scale rating at that time. CONCLUSIONS: The present findings are consistent with and support hypotheses suggesting that interactions between monoamine systems are altered in schizophrenia and that antipsychotic treatment may affect the functional balance between different monoamine neurotransmitters (although one should keep in mind factors other than interactions between monoamine systems that affect metabolite correlations and ratios.

Adult↗
PubMed1993

Dose-dependent effects of intravenous alprazolam on neuroendocrine, biochemical, cardiovascular, and behavioral parameters in humans.

Neuroendocrine, biochemical, cardiovascular, and behavioral parameters were assessed in seven normal volunteers for 2 h after intravenous administration of alprazolam (APZ). Three doses of APZ (0.003, 0.007, and 0.02 mg/kg) were administered to each subject in a random order with at least 4 days between infusions. Plasma growth hormone and sedation increased in a dose dependent manner after APZ, and there was a dose dependent change in the shape of the cortisol response to APZ. No dose-response relationships were evident for plasma ACTH and norepinephrine. These differences in dose-response relationships may reflect the involvement of multiple systems in controlling neuroendocrine, biochemical, and subjective responses to APZ infusion. The optimal dose of APZ needed to produce a neuroendocrine or behavioral change appears to differ depending on the parameter of interest.

Adult↗