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Biomedical subjects

F Karoum

Publications and source records attributed to F Karoum.

At least 55 records · Page 3Linked to original sources
PubMed1988

High intercorrelations among urinary outputs of norepinephrine and its major metabolites. A replication in depressed patients and controls.

We examined the intercorrelations among urinary outputs of norepinephrine (NE) and its three major metabolites in unipolar depressed patients (n = 28) and normal controls (n = 24). Among the depressed patients, levels of NE correlated with normetanephrine (NM), 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid (VMA), and VMA correlated with NM and MHPG. In the total group of depressed and control subjects (n = 52), the sum of NE and its major metabolites correlated with urinary outputs of NE, NM, MHPG, and VMA. These highly significant correlations among urinary outputs of NE and its major metabolites replicate a previous report of strong correlations among these same four urinary substances in a smaller group of depressed patients.

Adult↗
PubMed1988

Norepinephrine and its metabolites in cerebrospinal fluid, plasma, and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression.

Among 140 depressed and control subjects, there were significant positive correlations between indexes of noradrenergic activity in cerebrospinal fluid (CSF), plasma, and urine. Among the depressed patients, CSF levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and urinary outputs of NE and its metabolites normetanephrine, MHPG, and vanillylmandelic acid correlated significantly with plasma cortisol levels in relation to dexamethasone administration. Also, CSF levels of MHPG were significantly higher among patients who were cortisol nonsuppressors than among either patients who were cortisol suppressors or controls. Urinary outputs of NE and normetanephrine were significantly higher among patients who were cortisol nonsuppressors than among controls. Patients who were cortisol suppressors had indexes of NE metabolism similar to those of controls. These results in the depressed patients extend recent observations suggesting that dysregulation of the noradrenergic system and hypothalamic-pituitary-adrenal axis occur together in a subgroup of depressed patients.

Adult↗
PubMed1988

Central and peripheral effects of iminodipropionitrile on catecholamine metabolism in rats.

Chronic treatment with iminodipropionitrile (IDPN) causes a behavioral syndrome characterized by lateral and vertical neck dyskinesias, hyperactivity, random circling, and increased startle response (the "ECC syndrome"). The effects of the neurotoxin on norepinephrine (NE), dopamine (DA), and their metabolites were evaluated in the hypothalamus and the striatum of IDPN-treated animals. Urinary excretion of the amines was also measured. There was no significant persistent change in central metabolism of dopamine. There was a transient increase in NE metabolism in the hypothalamus after the third injection of IDPN that lasted until the development of the syndrome at 7 days of drug treatment. Urinary excretion of NE and its metabolites was increased on the day that the syndrome developed. Urinary excretion of homovanillic acid was persistently decreased throughout and after cessation of drug treatment. There was no change in the excretion of either dopamine or dihydroxyphenyl acetic acid. The ratio of total NE/total DA excreted by IDPN-treated rats was the inverse of that of control animals. These results suggest that persistent dyskinesias may be associated with a relative increase in facilitatory NE-dependent mechanisms at the cortical, subcortical, or spinal cord level.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Urinary-free cortisol in depressed patients and controls: relationship to urinary indices of noradrenergic function.

We measured urinary outputs of urinary-free cortisol in 28 medication-free depressed patients and 32 normal controls. Depressed patients had significantly greater urinary outputs of urinary-free cortisol than controls. Also, there were significant correlations among depressed patients, but not among controls, between urinary-free cortisol and urinary outputs of norepinephrine and its metabolite vanillylmandelic acid (VMA). These urinary data extend recent findings suggesting that dysregulation of both the hypothalamic-pituitary-adrenal axis and noradrenergic system occur together in depression.

Adult↗
PubMed1988

Thyrotropin releasing hormone test in unipolar depressed patients and controls: relationship to clinical and biologic variables.

We compared unipolar depressed patients (n = 31) with controls (n = 38) for their responses to the thyrotropin releasing hormone (TRH) test. Depressed patients showed significantly smaller thyrotropin stimulating hormone (TSH) responses to TRH which correlated negatively with post-dexamethasone plasma cortisol levels. Depressed patients also showed significant negative correlations between delta max TSH and urinary outputs of norepinephrine and normetanephrine with similar trends with plasma levels of norepinephrine and 3-methoxy-4-hydroxyphenylglycol. Patients who showed a blunted TSH response, compared with those who did not, had significantly lower platelet serotonin uptake values. These results suggest that the blunted TSH response to TRH seen in depression may be associated with dysregulation of the cortisol, noradrenergic and serotonin systems.

Adult↗
PubMed1987

Preliminary evidence of reduced combined output of dopamine and its metabolites in chronic schizophrenia.

The mean combined total body excretion of dopamine (DA) and its metabolites, measured by summing the molar excretion of DA and its metabolites in 24-hour urine samples (Sum DA), was reduced in 20 patients with schizophrenia who had not been receiving medication for at least two weeks. These patients were relatively resistant to treatment, as they were unable to live independently outside institutional settings despite conventional neuroleptic therapy. In contrast, sum norepinephrine (Sum NE), measured by summing the molar excretion of NE and its metabolites, was not reduced. These results are highlighted by expressing the data in terms of the ratio of Sum DA/Sum NE. Patients with schizophrenia had a significantly lower ratio. Treatment with haloperidol normalized the low ratio. Urinary excretion of 5-hydroxyindoleacetic acid was normal in the schizophrenic patients. These results suggest that chronic schizophrenia is more likely to be associated with a low rather than a high state of DA activity.

Adult↗
PubMed1987

Central catecholamines, cognitive impairment, and affective state in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy samples from older schizophrenic and control subjects for both the hypothalamus and the nucleus accumbens. The results of these analyses and demographic variables were regressed on antemortem measures of cognitive function and mood state. In the hypothalamus, there are significant direct relationships of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) with depressed mood, as measured by an adaptation of the Hamilton Rating Scale for depression. In the nucleus accumbens, dopamine (DA) and MHPG had significant inverse relationships with antemortem cognitive function, as measured by an adaptation of the Mini Mental State Exam. Results in this sample indicate that after controlling for age, the catecholamine concentrations accounted for approximately 50% of the variance in the antemortem measures of mood or cognition, depending on the loci measured.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Plasma phenylethylamine and phenylalanine in chronic schizophrenic patients.

The hypothesis that phenylethylamine (PEA) is an endogenous psychotogen in schizophrenics, particularly those with the paranoid subtype, has been previously studied by measuring PEA levels in urine and cerebrospinal fluid (CSF) of schizophrenic patients. However, plasma PEA may more accurately reflect simultaneous alterations of PEA in many organ systems, as might occur in a genetic disorder of PEA metabolism. No study to date has examined phenylalanine (Phe), which is thought to be a precursor of PEA, in the same patients who had PEA measured. In this study, we measure both plasma PEA and Phe in 17 drug-free schizophrenic patients and 17 matched controls. Plasma PEA in normal controls was found to be lower by three orders of magnitude compared to normal controls from previous studies--a finding that has not previously been reported. PEA was significantly lower in those schizophrenic patients who had a Research Diagnostic Criteria diagnosis of paranoid schizophrenia. PEA did not differ between patients and controls, and the correlation between plasma Phe and PEA was not significant.

Adult↗
PubMed1987

N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl.

In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on the excretion of NA and dopamine metabolites. These changes are opposite to the in vitro effects of pargyline on 5-HT, dopamine and NA oxidative deamination. Inhibitions of the metabolism of all the amines studied were clearly observed during chronic MAOI treatments, but these effects were less evident five days after the end of treatment, suggesting an almost normal metabolism of biogenic amines. It is concluded that while MAO inhibitors may be the primary compound responsible for MAO inhibition, the effects of their metabolites in some cases may also play equally important roles in the regulation of monoamines both in the periphery and the brain. Thus, as demonstrated here, NPB was found to be as potent as pargyline and deprenyl with regard to its in vivo MAO type B inhibitory properties.

Animals↗
PubMed1987

Treatment of hyperactive children with D-phenylalanine.

Eleven hyperactive boys were treated for 2 weeks with D-phenylalanine (20 mg/kg per day) and for 2 weeks with placebo in a double-blind crossover study. Tests included parent and teacher behavior ratings, cognitive measures, and blood and urine measures of norepinephrine, amino acids, and trace amines. No significant improvement or deterioration in behavior and no side effects were noted, and only serum phenylalanine was increased by the active treatment phase. This provides reassurance about the toxicity of aspartame, a food additive that contains phenylalanine, but argues against precursor loading treatment of hyperactivity.

Aspartame↗
PubMed1986

The effects of desipramine, zimelidine, electroconvulsive treatment and lithium on rat brain biogenic amines: a comparison with peripheral changes.

The effects of 4 common treatments for affective disorders on total body norepinephrine (NE) and dopamine (DA) turnover and metabolism were evaluated in rats. The treatments were chronic desipramine (DMI), zimelidine (ZMI), electroconvulsion (ECT) and lithium (Li). The central effects of ECT and Li were also assessed in the brain. The results obtained were compared with the effects of these 4 treatments on total NE (Sum NE) and DA (Sum DA) turnover in depressed patients. We have also evaluated central and/or peripheral effects of these treatments on phenylethylamine, p-tyramine and serotonin metabolism. The urinary changes in Sum NE and DA observed after DMI, ZMI and Li in the rat were similar to those found in depressed patients; Sum NE was significantly reduced. In contrast to its effects on depressed patients, chronic ECT significantly increased Sum NE. Similar to depressed patients, ECT reduced the fraction of NE escaping re-uptake in the rat. Sum DA was not affected by DMI, ZMI or ECT, but was significantly reduced by chronic Li treatment. All 4 treatments significantly reduced serotonin metabolism as indicated by reduced 5-hydroxyindoleacetic acid excretion rates. DMI, ZMI and Li treatments significantly reduced phenylethylamine urinary but not p-tyramine urinary outputs. The opposite effect was observed after ECT. Consistent with their effects on Sum NE, Li reduced while ECT increased hypothalamic NE turnover as deduced from the changes in 3-methoxy-4-hydroxyphenylglycol's rate of formation. As for Sum DA, Li had no effect on 3,4-dihydroxyphenylacetic acid or homovanillic acid's rates of formation in the caudate nucleus. Chronic ECT produced a small, but significant increase in homovanillic acid's rate of formation in the caudate nucleus.

3,4-Dihydroxyphenylacetic Acid↗
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

Urinary monoamines and monoamine metabolites in subtypes of unipolar depressive disorder and normal controls.

An examination was made of urinary catecholamine and metabolite outputs in 28 unipolar depressed patients and 25 normal controls. The total group of depressed patients had significantly higher urinary outputs of norepinephrine (NE) and its metabolite normetanephrine (NM), and significantly lower urinary outputs of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), than controls. Patients who met DSM-III criteria for a major depressive episode with melancholia (N = 8) had significantly higher urinary outputs of normetanephrine than controls, whereas patients with a major depressive episode without melancholia (N = 7) and dysthymic disorder patients (N = 8) had levels comparable with controls. We postulate that the higher urinary outputs of norepinephrine and its metabolite, normetanephrine, reflect dysregulation of the sympathetic nervous system in depression.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Relative activity of metabolic pathways for norepinephrine in endogenous depression.

Thirteen patients with endogenous depression, compared to 25 normal controls, had a significantly greater ratio of the urinary excretion of norepinephrine plus its metabolite normetanephrine to either the sum of the two urinary norepinephrine metabolites 3-methoxy-4-hydroxyphenylglycol plus vanillylmandelic acid or to the sum of urinary norepinephrine and all of its metabolites. As urinary levels of norepinephrine and normetanephrine are derived from an extraneuronal metabolic pathway, while levels of 3-methoxy-4-hydroxyphenylglycol and vanillylmandelic acid are more representative of total norepinephrine metabolism, these results suggest that there is a shift in endogenous depression to extraneuronal metabolic pathways for norepinephrine and its metabolites.

Adult↗
PubMed1986

Pemoline and urinary excretion of catecholamines and indoleamines in children with attention deficit disorder.

To test the hypothesis that any change in urinary noradrenergic excretion accompanies drug-induced improvement in attention deficit disorder with hyperactivity, the authors gave pemoline (mean dose, 2.9 mg/kg of body weight) to 11 boys with this disorder in a 4-week open trial. Pemoline administration improved behavior but did not significantly change urinary catecholamine excretion. Serotonin excretion was unchanged, but phenylethylamine (PEA) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased. Clinical responders and nonresponders did not differ with respect to baseline urinary monoamine excretion or change in PEA and 5-HIAA excretion.

Attention Deficit Disorder with Hyperactivity↗
PubMed1985

Metabolism of carbidopa to alpha-methyldopamine and alpha-methylnorepinephrine in rats.

Recent observations on the central and peripheral actions of carbidopa (CD) combined with our own results with the compound led us to examine its metabolism and effects on brain catecholamines in rats. CD was found to undergo a two-stage N-deamination process in vivo giving rise to alpha-methyldopa (AMD) and alpha-methyldopamine respectively. Further, beta-hydroxylation yielded alpha-methylnorepinephrine. These metabolic products were demonstrated in rat brain with reductions in norepinephrine and 3-methoxy-4-hydroxyphenylglycol, and little effect on dopamine. These results are consistent with the alpha-2 agonist effects of alpha-methylnorepinephrine. The relative formation of alpha-methyldopamine from CD was about 26% of an equivalent dose of AMD. It is concluded that some of the central effects of CD may be mediated by its metabolism to AMD, which readily crosses the blood-brain barrier. Possible implications of the findings are discussed.

Administration, Oral↗
PubMed1985

Stimulants, urinary catecholamines, and indoleamines in hyperactivity. A comparison of methylphenidate and dextroamphetamine.

Children with attention deficit disorder with hyperactivity were given either methylphenidate hydrochloride or dextroamphetamine sulfate to compare the effects on urinary excretion of catecholamines, indoleamines, and phenylethylamine (PEA). Methylphenidate's effects were distinctly different from those of dextroamphetamine. After methylphenidate administration, both norepinephrine (NE) and normetanephrine (NMN) concentrations were significantly elevated, and there was a 22% increase in excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG). In contrast, after dextroamphetamine treatment, MHPG excretion was significantly reduced and NE and NMN values were unchanged. Excretion of dopamine and metabolites was unchanged by either drug. Urinary PEA excretion was not significantly changed after methylphenidate treatment, but increased 1,600% in response to dextroamphetamine. Methylphenidate treatment did not significantly alter serotonin or 5-hydroxyindoleacetic acid excretion. Effects of dextroamphetamine were not tested.

3,4-Dihydroxyphenylacetic Acid↗