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Biomedical subjects

W Z Potter

Publications and source records attributed to W Z Potter.

At least 163 records · Page 9Linked to original sources
PubMed1985

Exaggerated orthostatic responsivity of plasma norepinephrine in depression.

An orthostatic challenge paradigm was used to assess noradrenergic regulation in depressive disorders. Plasma norepinephrine (NE) concentrations and concurrent blood pressure and pulse were measured at rest and after five minutes of standing in groups of bipolar (N = 22) and unipolar (N = 19) depressives and in 12 partially age-matched healthy female volunteers. Supine plasma NE levels were significantly lower in bipolar patients than in either unipolar depressives or normal volunteers. Following the orthostatic challenge, the fractional NE increase in both patient groups--particularly the bipolar group--was greatly exaggerated, exceeding that in the controls by approximately 100%. Nonetheless, the postural cardiovascular changes--elevations of diastolic blood pressure and heart rate--failed to distinguish the three subject groups. Noradrenergic dysregulation in depression thus is characterized by inefficient hyperreactivity to physiologic stress.

Adult↗
PubMed1985

The effect of clorgyline on noradrenergic function.

A low dosage of the specific MAO-A inhibitor clorgyline (5-10 mg/day) was administered chronically to 10 depressed patients. Peripheral noradrenergic activity, as assessed by measurements of the plasma norepinephrine (NE) concentration, heart rate, and blood pressure, was determined before and after drug treatment. The administration of a low dosage of clorgyline was associated with a decrement in peripheral presynaptic noradrenergic activity. Comparison with the results of similar studies of the effects of desmethylimipramine (DMI) suggests that antidepressant drugs with unrelated primary actions affect peripheral noradrenergic functions differently.

Adult↗
PubMed1985

Differences in lithium effects in depressed and healthy subjects.

To evaluate the neurotransmitter actions of lithium without the confounding biochemical abnormalities associated with affective disorders, Li was given to 12 hospitalized healthy young men. After a 600-mg loading dose, subjects were placed on "therapeutic" Li doses averaging 1225 +/- 300 mg for 1 wk, reaching steady-state plasma levels of 0.82 +/- 0.17 mEq/l. Cardiovascular function at rest and diastolic blood pressure and pulse on standing were not altered by Li. Average baseline plasma norepinephrine (NE) concentration in the supine position (1.07 +/- 0.50 pmol/ml) did not change after 1 wk of Li dosing (1.16 +/- 0.57 pmol/ml). There was similar variability, without mean change, in plasma NE increments after orthostatic challenge and in plasma 3-methoxy-4-hydroxyphenylglycol concentrations before and during Li dosing. Urine volume was stable throughout the week of drug dosing, during which daily NE excretion was constant. In contrast to earlier data obtained in patients with depression receiving Li, there were no Li-related decrements in average whole-body NE or dopamine turnover. Mean daily urinary excretion rates of serotonin and its major metabolite 5-hydroxyindoleacetic acid did not change throughout the study. Our and other studies suggest that Li has a corrective action in patients with depression and hypothesized neurotransmitter abnormalities, but Li does not affect individuals without affective disorders.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Interethnic dissociation between debrisoquine and desipramine hydroxylation.

Chinese and Caucasian volunteers who had previously participated in a single dose desipramine pharmacokinetic study underwent debrisoquine hydroxylation phenotyping. After a single 10-mg oral dose of debrisoquine, urinary concentrations of the drug and its major metabolite, 4-hydroxy-debrisoquine (4-OHD), from an 8-hour collection were more variable in the Caucasians. Compared to the Chinese, the Caucasian subjects tended to excrete higher mean fractions of the dose as unchanged debrisoquine (10.9 +/- 8.8% vs. 6.3 +/- 2.6%) and 4-OHD (15.9 +/- 13.0% vs. 9.7 +/- 7.7%), although given the high variability the differences did not reach significance. The "metabolic ratio" of urinary debrisoquine to 4-OHD was less than 3 in all 20 subjects, indicating extensive debrisoquine hydroxylation in every volunteer, including two Chinese individuals known to display slow clearance of desipramine. Contrary to expectation, debrisoquine hydroxylation did not correlate with total or hydroxylation clearance of desipramine in either ethnic group singly or combined. This finding is not consistent with assumptions about the genetic equivalence of the primary metabolic pathways of debrisoquine and desipramine.

Adult↗
PubMed1985

Psychoses associated with bupropion treatment.

The authors describe the development of acute psychoses in four patients treated with bupropion, a unicyclic aminoketone antidepressant. In two of the cases the psychoses seemed to be affected by dose. The mechanism responsible for the psychotic reactions is unclear, although it may involve perturbation of dopaminergic systems. On the basis of their experience, the authors offer recommendations regarding the clinical use of bupropion.

Acute Disease↗
PubMed1984

The effect of desmethylimipramine on the metabolism of norepinephrine.

Eleven normal volunteers were given an acute and two chronic doses of desipramine (DMI). The plasma norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), and dihydroxyphenylglycol (DHPG) concentrations were measured before and during drug administration. DMI reduced plasma concentrations of MHPG by 13% and DHPG by 17%. After two weeks of drug administration, the MHPG/NE ratio was reduced, and there was a significant negative correlation with the concurrent drug concentration. These results suggest that DMI: (1) reduces the turnover of NE; and (2) diminishes the oxidative deamination of NE. In addition, the drug concentration response relationship indicates that the effects of uptake inhibition may not be maximal until concentrations in the apparent therapeutic range are achieved.

Adult↗
PubMed1984

Urinary 3-methoxy-4-hydroxyphenylglycol and major affective disorders. A replication and new findings.

We studied group and subgroup differences in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with major affective disorder (66 depressed, 13 manic) and normal volunteers (27 subjects). Bipolar I depressed patients excreted less MHPG than unipolar depressed patients, manic patients, or normal volunteers. The mean (+/- SEM) MHPG excretion rate was 1.44 +/- 0.10 mg/day in 19 depressed bipolar I patients, 1.79 +/- 0.11 mg/day in 28 unipolar depressed patients, 2.11 +/- 0.19 mg/day in 13 manic patients, and 1.85 +/- 0.12 mg/day in 27 normal volunteers. Other sources of variance that affected urinary MHPG levels did not explain subgroup or state differences. There was only a trend for a low pretreatment MHPG level to be associated with positive response to imipramine hydrochloride or desipramine hydrochloride in the 19 patients treated with these drugs. The application of this biological test value for prediction of differential response to antidepressant drugs would therefore seem premature.

Adult↗
PubMed1984

Five antidepressant treatments in depressed patients. Effects on urinary serotonin and 5-hydroxyindoleacetic acid output.

The 24-hour urinary serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) outputs were repeatedly measured in 21 patients with major affective disorders after a minimum of three weeks free of drug treatments and at steady state during subsequent antidepressant treatments or during the second week after a series of electroconvulsive treatments (ECTs). The 5-HIAA outputs were more variable over time than the outputs of major catecholamine metabolites, previously studied by us. Patients with rapid mood cycles excreted large amounts of 5-HT. Lithium carbonate and ECTs reduced the outputs of 5-HT and 5-HIAA, respectively. Lithium carbonate also stabilized the output of 5-HT. No common effect of different antidepressant treatments on indole outputs was found.

Antidepressive Agents↗
PubMed1984

Hormonal responses to zimelidine and desipramine in depressed patients.

Plasma prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and cortisol were repeatedly measured during the morning over a 4-hour period in patients who received single or chronic doses of desipramine (DMI) or zimelidine (ZIM). Preclinical studies had suggested that DMI, an uptake inhibitor specific for norepinephrine, would have different effects than ZIM, a selective serotinin uptake inhibitor. The GH response to DMI was blunted in the depressed patients. Neither DMI nor ZIM produced changes in LH or cortisol. DMI acutely increased plasma PRL, whereas ZIM had an effect only after chronic pretreatment. Chronic DMI but not ZIM increased baseline PRL. The patterns and magnitude of responses raise questions concerning the role of serotonin and norepinephrine in PRL release in man and the applicability of current preclinical models.

Adolescent↗
PubMed1984

Common mechanism of action of biochemically "specific" antidepressants.

NE turnover in depressed patients treated with three drugs which have specifically different primary biochemical effects is compared before and after treatment. Turnover is quantitated as the sum of NE and its major metabolites excreted in the urine using a new mass spectrometric assay. Clorgyline , a MAOI specific for Type A; desipramine, a selective NE uptake inhibitor; and zimelidine, a selective 5HT uptake inhibitor, were used. All three antidepressants, including zimelidine, reduced NE turnover although producing very different effects on the metabolic profile of NE. It remains likely that effects on NE are related to therapeutic effect.

Adult↗
PubMed1984

Desipramine pharmacokinetics in Chinese and Caucasian volunteers.

In order to better define the role of pharmacokinetic variation in reported cross-ethnic differences in dosing patterns of some psychoactive drugs, single dose kinetics of the tricyclic antidepressant desipramine (DMI) were studied in 14 Chinese and 16 Caucasian healthy volunteers. DMI and 2-OH-DMI concentrations were assayed with h.p.l.c. in serial plasma and 24 h urine samples over 5 days following an oral 100 mg dose of DMI. Mean total clearance of DMI ( CLDMI ) from plasma was significantly (P less than 0.05) higher in the Caucasians (123 +/- 57 l/h) than in the Chinese (73.5 +/- 38.8 l/h). There was no significant difference in the apparent clearance of DMI by hydroxylation, fraction of dose metabolized to the hydroxy metabolite, DMI t1/2 or plasma protein binding between the two groups. Trimodal distribution of CLDMI was found, with 4/14 (29%) Chinese demonstrating slow CL (less than 33 l/h) and 4/16 (25%) Caucasians rapid CL (greater than 195 l/h). Correcting CL values for the greater mean weight of the Caucasians did not alter the pattern of distribution. CLDMI did not correlate with body weight. Although environmental factors cannot be ruled out, these results are consistent with genetically based differences in hepatic metabolism, probably affecting pathways in addition to hydroxylation, and suggest that 30% of Orientals would be at risk for toxicity from routine doses of tricyclics or similarly metabolized drugs.

Adult↗
PubMed1984

Amelioration of psychosis with carbidopa. A case report.

We have recently demonstrated that some patients with atypical bipolar affective disorders, characterized by psychotic manias and depressions, have fluctuating and episodic high urinary phenylethlamine (PEA) excretion. We treated a 30 year old woman, who has this disorder, with 200 mg/24 hours of carbidopa. Her psychosis was ameliorated and the urinary PEA output stabilized to a low normal level. Upon withdrawal of carbidopa her psychosis worsened and improved again when carbidopa treatment was reinstated. Carbidopa did not affect the duration or severity of the patient's mood cycles.

Adult↗
PubMed1984

Psychotherapeutic drugs and biogenic amines. Current concepts and therapeutic implications.

Over the last 2 decades evidence has continued to accumulate from studies in various model systems that drugs effective in the treatment of major psychiatric disorders alter biogenic amines which function as neurotransmitters. As a result of these findings, various hypotheses have been formulated that there is a fundamental abnormality of one or another of the biogenic amine systems (i.e. the serotonergic, noradrenergic and dopaminergic systems) in the affective disorders and schizophrenia. Numerous attempts have been made to assess these biogenic amine hypotheses, primarily through quantitation of the major metabolites of the amines and recently by assessment of receptor sensitivity or density. The combination of basic pharmacological and clinical research has shown that there are biochemical subtypes, especially among those with affective illness, which might show a preferential response to biochemically specific drugs. If verified, such research constitutes a significant therapeutic advance. The status of these investigations is critically assessed in this review. Finally, many new techniques, challenge tests and biochemically distinct drugs are being introduced. Promising approaches that are likely to produce refinements of the biogenic amine hypotheses, as well as suggesting alternative formulations, are reviewed.

Antidepressive Agents↗
PubMed1984

Reduction of norepinephrine turnover by serotonergic drug in man.

Zimelidine (ZIM), a relatively specific serotonin reuptake inhibitor, was administered to 12 hospitalized healthy young male volunteers. Chronic but not acute ZIM caused a modest (23%) but significant elevation of plasma norepinephrine (NE) measured in the standing but not in the supine position. The 24-hr urinary excretion of NE itself was unchanged on chronic drug, whereas "whole-body" NE turnover was reduced by 1 week of ZIM, as evidenced by lowered excretion rates (both individually and summed with NE) of the metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NM), and vanillylmandelic acid. Lack of effect of ZIM on the NM/MHPG excretion ratio (which is increased by desipramine) indicated that ZIM and its major metabolite, horzimelidine (NZIM) are not acting by NE reuptake blockade. These data are consistent with modulating serotonergic influence on the noradrenergic system. Reduction of NE turnover and increasing the efficiency of the NE neurotransmission may be a common pathway of all clinically effective antidepressant treatments.

Adult↗
PubMed1984

Active metabolites of antidepressants: pharmacodynamics and relevant pharmacokinetics.

This chapter offers a current assessment of the relevance of new findings on the pharmacodynamics and pharmacokinetics of active metabolites of the tricyclic antidepressants. The assessment of TCA actions that may be additive, synergistic, or antagonistic requires precise knowledge of pharmacodynamic potency and control of pharmacokinetic behavior. Simple assumptions about the behavior of ratios of active forms across the populations are inappropriate. Careful pharmacokinetic control is necessary, especially considering that such variables as age, race, illness and other drugs can subtly influence the overall effect by influencing a single active form. The hydroxy metabolites are most susceptible since both their formation and elimination utilize independent variable pathways. Nonetheless, it is now possible to quantitate all known active forms of TCAs. Clinical investigation of the relationship between these forms and specific biochemical effects should provide advances in our understanding of antidepressant mechanisms. On the basis of available data of this type, we conclude that an intensified effort to understand effects secondary to NE uptake inhibition alone would be especially valuable.

Adult↗
PubMed1984

Second-generation antidepressants.

The host of newly developed antidepressant drugs offer important clinical advantages to some patients, although their promises of improved therapeutic efficacy and reduced adverse effects compared with conventional treatments are not fully realized. Increased biochemical specificity and unique mechanistic or clinical profiles render these compounds valuable in research into the pathophysiology of affective disorders and mode of action of antidepressant agents.

Alprazolam↗