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Biomedical subjects

F Karoum

Publications and source records attributed to F Karoum.

At least 73 records · Page 4Linked to original sources
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

Biochemical effects of L-deprenyl in atypical depressives.

To examine the biochemical effects of 10-30 mg/day L-deprenyl, measurement of 24-hr urinary output of phenylethylamine (PEA), 3-methoxy 4-hydroxy phenylethyleneglycol (MHPG), and L-deprenyl's amphetamine metabolites were carried out before and during the treatment of atypical depressives. Platelet monoamine oxidase (MAO) activity was also assessed. With L-deprenyl 10-30 mg/day, the expected MAO B inhibition occurred, as indicated by significant increase in urinary PEA excretion and virtual disappearance of platelet MAO activity. Twenty-five to 33% of the daily dose of L-deprenyl was recovered as urinary methamphetamine or amphetamine. Excretion of MHPG was significantly decreased with L-deprenyl 10-20 mg/day. Overall, the results suggest that L-deprenyl's antidepressant effects are mediated by some mechanism other than, or in addition to, MAO B inhibition.

Adult↗
PubMed1985

Effect of chlordecone (Kepone) on the rat brain concentration of 3-methoxy-4-hydroxyphenylglycol: evidence for a possible involvement of the norepinephrine system in chlordecone-induced tremor.

3-Methoxy-4-hydroxyphenylglycol (MHPG) is the major metabolite of norepinephrine (NE) in the rat brain. A single injection of tremorigenic doses of chlordecone to adult male Fischer-344 rats resulted in significant increases in MHPG concentrations in hypothalamus, brain stem, cerebellum, and caudate nucleus. The increase in MHPG was accompanied by a decrease in NE in the hypothalamus, suggesting that chlordecone treatment caused an increase in the turnover of NE in the brain. There was a dose- and time-related correlation between the increases in the concentrations of MHPG in hypothalamus, brain stem, and cerebellum and tremor in rats. The increase in MHPG in hypothalamus and brain stem occurred as early as 1 hr postdosing; this preceded the earliest measurable sign of tremor and initial hypothermia. Whether the alterations in the brain NE system are involved in the expression of the tremor and the initial hypothermia induced by chlordecone or whether they are merely associated with these changes is not clear.

Animals↗
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

Postmortem central catecholamines and antemortem cognitive impairment in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy brain samples from 19 elderly schizophrenic patients and controls. Data from the hypothalamus and nucleus accumbens demonstrate altered catecholamine metabolism associated with cognitive impairment in these subjects. Both loci show decrements of norepinephrine concentrations, while the nucleus accumbens samples also show increased dopamine, dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylglycol concentrations associated with dementia in these subjects. The data argue for examination of catecholamine metabolism with respect to dementia in a broad range of elderly subjects.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Reduced metabolism and turnover rates of rat brain dopamine, norepinephrine and serotonin by chronic desipramine and zimelidine treatments.

As part of of an ongoing effort to compare changes in whole body turnover of catecholamines and serotonin in man with those induced by antidepressants in the rat brain, we have evaluated the chronic effects of desipramine (DMI) and zimelidine (ZMI) on brain catecholamines and serotonin in the rat. The amines and metabolites measured include norepinephrine (NE), dopamine (DA) and their metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Three brain areas were analysed; the hypothalamus, caudate nucleus and frontal cortex. Chronic DMI and ZMI reduced hypothalamic MHPG and caudate nucleus DA metabolites, in particular HVA. Both drugs reduced NE and DA turnover rates (estimated after alpha-methyl-p-tyrosine injection) and the rate of MHPG formation in the hypothalamus (estimated after pargyline treatment). They did not change NE turnover rate, but reduced DA turnover rate and rate of HVA formation in the caudate nucleus. Chronic DMI but not ZMI reduced DOPAC rate of formation in the caudate nucleus. Apparently changes in DA turnover and metabolism produced by these antidepressants are better related to changes in HVA than DOPAC concentrations. Similar to their influence on hypothalamic and caudate nucleus catecholamines, both chronic DMI and ZMI produced changes in serotonin concentration in the caudate nucleus and frontal cortex serotonin that suggest a reduction in its turnover rate and metabolism. The reduction in NE turnover in hypothalamus is consistent with the effects of chronic DMI and ZMI on whole body NE turnover observed in man.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Phenylethylamine excretion in depression.

Urinary phenylethylamine (PEA) excretion was evaluated in two populations of depressed hospitalized patients. Seven of 53 patients had PEA values exceeding three times the highest value found in 16 normal controls. The patients with high PEA excretion were all females. They were not, however, otherwise clinically distinguishable from depressed patients with low PEA. In a subsample of 31 patients and 10 controls, PEA excretion was not correlated with phenylacetic acid (PAA) excretion. These results suggest that depression is not associated with a generalized PEA deficit and that PAA reductions, previously reported in a depressed patient population, may not reflect a PEA abnormality.

Adolescent↗
PubMed1984

Seasonal variation in human central dopamine activity.

This report focuses on two studies of seasonal variation of central dopamine activity in patients with schizophrenia and normal controls. In the two investigations, data were grouped and analyzed by season (i.e., spring-summer vs. fall-winter). The first study concerned blink rate, a putative measure of central dopamine activity; the blink rate for patients with schizophrenia was significantly increased during the spring-summer period. In the second study concentrations of catecholamines and their metabolites were measured in the hypothalamus and nucleus accumbens of normal and schizophrenic subjects. Findings include a reduced concentration of hypothalamus dopamine in normal controls and a reduced concentration of homovanillic acid in the nucleus accumbens of patients with schizophrenia, both during the spring-summer period.

Adult↗
PubMed1984

The Genain Quadruplets 25 years later: a diagnostic and biochemical followup.

A biological and clinical followup of the Genain Quadruplets was initiated as a multilaboratory collaborative effort at the National Institute of Mental Health (NIMH). The quadruplets are 51-year-old monozygotic women previously studied with a battery of psychological and physiological tests 25 years ago at the NIMH. The present article (the first of a series of three) details the clinical history and course of the schizophrenic illness in each of the quadruplets and describes the biochemical measures determined. The findings of elevated urinary phenylethylamine excretion, decreased plasma dopamine-beta-hydroxylase activity, and increased alpha-adrenergic receptor concentrations in all quadruplets warrant further genetic studies.

3,4-Dihydroxyphenylacetic Acid↗
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

Low dose bromocriptine: a study of acute effects in chronic mediated schizophrenics.

An acute low oral dose (2 mg) of bromocriptine was administered in a randomized double blind fashion to 11 chronic symptomatic mediated schizophrenic patients. There was an overall improvement for the group on the Brief Psychiatric Rating Scale (BPRS) following bromocriptine. Plasma homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, and vanilloyl-mandelic acid concentrations were unchanged after bromocriptine. Bromocriptine concentrations in the plasma showed a large inter-individual variation. There was a significant inverse correlation between plasma bromocriptine concentration and total BPRS score at 60 minutes post-bromocriptine administration. These results suggest a need for further replication in a larger study population and a need for controlled studies with chronic administration of low dose bromocriptine in chronic medicated schizophrenic patients.

Adult↗
PubMed1984

Depression during methadone withdrawal: no role for beta-phenylethylamine.

An atypical depression, resembling beta-phenylethylamine (PEA) deficiency states, frequently complicates methadone withdrawal. We undertook a study of 24-h urinary free PEA excretion in steady-dosed and withdrawing methadone patients, hypothesizing that abstinent patients would excrete less PEA than controls and that methadone would show a dose-dependent effect on PEA turnover. As hepatic dysfunction, frequent in methadone patients, might affect PEA turnover, we also evaluated liver chemistries, [13C]aminopyrine excretion, 2-hydroxylation of estradiol, and 'blind', global severity ratings in each subject. PEA excretion did not significantly differ between eight fully detoxified methadone patients (median 4.76 micrograms/24 h) and seven normal controls (median 5.80 micrograms/24 h). Moreover, PEA excretion bore no relation to methadone dosage among 24 steady-dosed subjects. PEA excretion in seven withdrawing subjects each receiving 4-8 different doses of methadone similarly showed no relation to dose. Despite significant liver disease, several measures of impairment did not correlate with PEA excretion. These findings argue against a role for PEA deficiency in withdrawal depression.

2-Hydroxyphenethylamine↗
PubMed1984

Urinary phenethylamine response to d-amphetamine in 12 boys with attention deficit disorder.

Urinary phenethylamine (PEA), an endogenous amine similar to amphetamine in both molecular structure and pharmacological properties, was studied in 12 boys with attention deficit disorder with hyperactivity. d-Amphetamine and placebo were given for 14 days each in a counterbalanced crossover design; double-blind teacher behavior ratings and motor activity measurements were also obtained. Excretion of PEA, phenylacetic acid, creatinine, and d-amphetamine were measured. PEA was significantly increased and phenylacetic acid was unchanged after d-amphetamine administration, and change in PEA excretion correlated significantly with d-amphetamine excretion. There was no significant relationship between either clinical response to drug and change in PEA or phenylacetic acid excretion.

Attention Deficit Disorder with Hyperactivity↗
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

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↗