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Biomedical subjects

W Z Potter

Publications and source records attributed to W Z Potter.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effects of psychotropic drugs on neurotransmitters in man.

Primary biochemical profiles of antidepressants and neuroleptics are summarized in comparison to their actual effects on monoamine neurotransmitters in humans during the time period when clinical response emerges. Even the most biochemically specific of these drugs produces effects on at least two monoamines by three to four weeks. Interestingly, taking into account relative changes in dopamine and serotonin metabolites in cerebrospinal fluid relates better to the primary biochemical action(s) of each drug than do absolute changes. Moreover, monoamine changes after drugs are in the opposite direction to those after ECT, suggesting that balance among rather than shifts in single neurotransmitters is the relevant target of major psychotropic drugs.

Antidepressive Agents↗
PubMed1987

Dopamine D1 receptor in rat brain: a quantitative autoradiographic study with 125I-SCH 23982.

We report the regional distribution and characteristics of 125I-SCH 23982 binding to D1 receptors in rat brain using a quantitative autoradiographic technique. The substantia nigra pars reticulata, the caudate putamen, the nucleus accumbens and the olfactory tubercle had a single class of high affinity binding sites for 125I-SCH 23982. Binding sites were also present in a discrete, continuous band connecting the caudate putamen with the substantia nigra.

Animals↗
PubMed1987

Monoamine neurotransmitter interactions and the prediction of antidepressant response.

Clinical studies of monoamine neurotransmitter function in depression have concentrated on individual monoamines without focusing on interactions between monoamine systems. Virtually all modern studies have found significant correlations between monoamine metabolite concentrations in cerebrospinal fluid (CSF). These correlations should in part reflect interactions between central monoamine systems. In the present analysis, CSF had been obtained from depressed patients before (n = 40) and after (n = 36) antidepressant treatment. The patients were grouped based on their response to treatment. Absolute concentrations of CSF monoamine metabolites (homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol) did not differ between the two groups before or after treatment. However, when correlations between metabolites were compared, nonresponders to treatment differed considerably from responders. In responders, as in previously described normal populations, all three metabolites correlated with one another before and after treatment, and treatment-induced changes in metabolite concentrations also correlated with one another. In contrast, metabolites in nonresponders did not correlate with one another before treatment, nor did treatment-induced changes correlate with one another in this group. Furthermore, correlations between treatment-induced changes in metabolites differed significantly between responders and nonresponders, and there was a trend for pretreatment correlations to differ as well. The lack of correlation between monoamine metabolites in nonresponders suggests that interactions between monoamine systems may be disrupted in these individuals. Using CSF metabolite correlations to study neurotransmitter interactions may have clinical relevance and yields information not available from examining neurotransmitters in isolation.

Adult↗
PubMed1987

The effects of antidepressants on the cerebrospinal fluid homovanillic acid/5-hydroxyindoleacetic acid ratio.

Dopamine and serotonin systems are morphologically interconnected in the midbrain. Several studies have also demonstrated a functional relationship between these two monoamine systems. Concentrations of their metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA), consistently correlate with one another in human cerebrospinal fluid. Previous studies of the effects of antidepressants on the dopamine and serotonin systems have focused on the two systems in isolation without considering the interactions between the two. One way of taking this interaction into account may be to form a ratio of dopamine and serotonin measures. The present study measured HVA and 5HIAA in cerebrospinal fluid of 31 patients with depression and 12 patients with Alzheimer's disease before and after treatment with a variety of antidepressant drugs. The ratio of HVA/5HIAA was able to discriminate much more powerfully between effects of different drugs than HVA or 5HIAA examined separately.

Alzheimer Disease↗
PubMed1986

Circadian covariation of norepinephrine and serotonin in the locus coeruleus and dorsal raphe nucleus in the rat.

We report robust correlations between concentrations of the neurotransmitters norepinephrine and serotonin in the locus coeruleus and the dorsal raphe nucleus of the brainstem in rats analyzed at 7 different time points over 24 h. We found similar circadian rhythmicities for both monoamines with acrophases just before the onset of the dark period. The monoamine concentrations diminished and the significant intercorrelation between norepinephrine and serotonin in the locus coeruleus disappeared during the night suggestive of a noradrenergic stimulation of dorsal raphe serotonin during the day. Timing of experiments is crucially important in studies on brain monoaminergic indices and their interrelationships.

Animals↗
PubMed1986

Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF.

The repeatedly observed strong positive correlation between 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in human cerebrospinal fluid (CSF) prompted an investigation to see if conclusions concerning possible interactions between brain serotonin and dopamine turnover could be reached from human CSF concentrations of these acid metabolites. CSF data from patients with depressive disorders diagnosed according to the RDC from Sweden (n = 140) and from the National Institute of Mental Health (n = 35) were used to test structural hypotheses by two statistical approaches--LISREL analysis and logistic regression. Results from both men and women were unequivocal: 5HIAA "controls" HVA, interpretable as a regulatory action of serotonin turnover on dopamine turnover. In women, only 5HIAA was affected by age, height and body size (higher in elderly, short and stout women); no similar relationships were seen in males. The concept of a serotonergic regulation of dopamine turnover was tested on brain punch analyses of serotonin and dopamine and their metabolites in two sets of dogs in a large number of brain areas. Results confirm a facilatory effect of serotonin on indices of dopamine turnover in many brain regions, especially brain stem and hypothalamus. The animal data validate the data analytic approach in humans.

Adolescent↗
PubMed1986

Clinical studies on norepinephrine metabolism: how to interpret the numbers.

Metabolism, synthesis rates, and pharmacokinetics of major metabolites of endogenous norepinephrine were investigated in 38 drug-free depressed patients receiving a low monoamine diet on a closed ward. In a group of 21 patients, plasma and cerebrospinal fluid (CSF) concentrations of 3-methoxy-4-hydroxyphenyl-glycol (MHPG) correlated positively, but not significantly. In two groups of eight patients each, effects of desipramine and zimelidine on the central production rate of MHPG were examined using CSF and urine data. Both desipramine and zimelidine significantly reduced the central production rate of MHPG.

Adult↗
PubMed1986

Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers.

S-adenosyl-methionine (SAMe) is currently undergoing trials as a possible antidepressant. Because SAMe's mechanism of action is obscure and norepinephrine (NE) is often implicated in affective disorders, we studied the effects of SAMe on this neurotransmitter in volunteers. Plasma NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the supine and standing position were studied before and after acute placebo or a single 400 mg dose of SAMe and following seven daily administrations; concomitant measures were heart rate (HR) and blood pressure. Subjects were unable to distinguish acute drug from placebo, and although chronic SAMe administration was open, they reported no behavioral effects. Standing HR and plasma NE were reduced following chronic SAMe. Qualitatively similar changes are obtained following chronic treatment with monoamine oxidase inhibitors (MAOIs). However, unlike MAOIs, chronic SAMe treatment was not associated with changes in plasma MHPG. Exaggerated standing NE is found in depressed patients; SAMe may reduce this abnormal response, providing a clue for its mechanism of action in depression.

Adolescent↗
PubMed1986

Treatment of childhood hyperactivity with desipramine: plasma drug concentration, cardiovascular effects, plasma and urinary catecholamine levels, and clinical response.

Twenty-nine boys with attention deficit disorder/hyperactivity were randomly assigned to receive desipramine (DMI; n = 17) or placebo (n = 12) for 14 days in a noncrossover, double-blind study. There was immediate behavioral improvement with DMI at day 3 that was sustained for 2 weeks; behavioral improvement did not correlate with plasma concentrations of DMI, hydroxy-DMI, or their sum at either days 3 or 14. There were no untoward side effects; there was a drug-induced increase in pulse and diastolic blood pressure. During drug therapy, the urinary excretion of norepinephrine, vanillymandelic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) was decreased at both days 3 and 14. The plasma MHPG level was decreased at days 3 and 14 and (standing) plasma NE levels increased at day 14. The decreases in both urinary and plasma MHPG levels showed significant correlations with behavioral improvement during the second week. These data corroborate previous findings on sympathomimetic effects of tricyclic antidepressants in children and support a noradrenergic mechanism in the mediation of drug effects on attention deficit disorder/hyperactivity.

Administration, Oral↗
PubMed1986

Neurochemical and neuroendocrine dysregulation in affective disorders.

Depressed patients demonstrate dysregulation in multiple neurochemical and neuroendocrine systems. The observed abnormalities are often subtle, involving "inefficiencies" in stress-responsive systems. Norepinephrine, acetylcholine, the hypothalamic-pituitary-adrenal axis, and the hypothalamic-pituitary-thyroid axis are among the major biochemical and hormonal sites of dysregulation in depression.

Acetylcholine↗
PubMed1985

Evaluation of zimeldine in Alzheimer's disease. Cognitive and biochemical measures.

Neuropsychological and neurochemical effects of zimeldine, a relatively specific serotonin reuptake blocker, were examined in four patients with clinically diagnosed Alzheimer's disease, in a double-blind, placebo-controlled, crossover study. Individualized doses of zimeldine were administered to achieve target plasma zimeldine concentrations of approximately 50 (low) to 100 (high) ng/mL. Overall, there was no significant effect of zimeldine on memory or reaction time measures as compared with placebo. The drug significantly reduced (by up to 38%) 5-hydroxyindoleacetic acid concentrations in the cereobrospinal fluid and almost abolished (90% reduction) platelet serotonin uptake. Cerebrospinal fluid concentrations of 3-methoxy-4-hydroxy-phenylglycol, a major metabolite of norepinephrine, and homovanillic acid, the major metabolite of dopamine, were not altered. Our findings indicate that alterations in central and peripheral serotoninergic function by a serotonin reuptake blocker (zimeldine) are unaccompanied by measurable changes in memory and/or reaction time in patients presumed to have Alzheimer's disease.

Aged↗
PubMed1985

Treatment of hyperactive children with monoamine oxidase inhibitors. II. Plasma and urinary monoamine findings after treatment.

Urinary monoamines and metabolites as well as plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol were measured in 14 boys (mean age, 9.2 years) with Attention Deficit Disorder With Hyperactivity during an initial placebo period, after four weeks of treatment with either dextroamphetamine sulfate (N=5) or a monoamine oxidase inhibitor (N=9) and at the end of a subsequent two-week placebo "washout" period. Both dextroamphetamine and monoamine oxidase inhibitors produced persistent changes in monoamines and metabolites, which were most marked and consistent for NE and its metabolite 3-methoxy-4-hydroxyphenylglycol. These changes did not correlate in a consistent fashion with clinical response during drug treatment. Moreover, there was rapid clinical relapse following cessation of either treatment while the alterations in NE metabolism remained during the two weeks following drug, further demonstrating the independence of these changes from clinical state. Future studies with dextroamphetamine need drug-free periods that are greater than 14 days to obtain true "baseline" conditions.

Amines↗
PubMed1985

Selective antidepressants and cerebrospinal fluid. Lack of specificity on norepinephrine and serotonin metabolites.

Cerebrospinal fluid concentrations of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid, were measured in depressed patients before and after treatment with three putatively specific antidepressants. The expected specificity of action on these three neurotransmitter metabolites was not observed. Desipramine hydrochloride, a norepinephrine uptake inhibitor, reduced 5-HIAA as well as MHPG concentrations; zimeldine hydrochloride, a serotonin uptake inhibitor, reduced MHPG as well as 5-HIAA concentrations; and clorgyline, a selective monoamine oxidase type A inhibitor, which might be predicted to most affect 5-HIAA, dramatically reduced MHPG, moderately reduced homovanillic acid, and only modestly reduced 5-HIAA concentrations.

Adolescent↗
PubMed1985

Plasma norepinephrine level in affective disorders. Relationship to melancholia.

The plasma norepinephrine (NE) level was measured in 45 depressed patients and in 41 normal control subjects. Patients who met DSM-III criteria for a major depressive episode with melancholia (MDE-MEL; N = 16), and those with MDE but with melancholia in a previous episode (MDE-PMEL; N = 8), had significantly higher levels of plasma NE than normal control subjects while lying and standing and a greater change in the levels; whereas, patients with MDE alone (N = 10) and patients with dysthymic disorder (N = 11) had levels of NE comparable with control levels. Bipolar patients (N = 7), all with current melancholia or a history of it, had significantly lower levels of NE while lying down or standing than depressed unipolar patients with similar histories of melancholia. Among unipolar patients with melancholia, nonsuppressors on the dexamethasone suppression test had significantly higher lying-down NE values than did suppressors, suggesting that dysregulation of both the hypothalamic-pituitary-adrenal axis and the peripheral sympathetic nervous system occur together in this subgroup of depressed patients.

Adult↗