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Biomedical subjects

F Karoum

Publications and source records attributed to F Karoum.

At least 91 records · Page 5Linked to original sources

Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man.

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.

Carbidopa↗

Catecholamine content of intracerebral adrenal medulla grafts.

The rotational behavior which is produced by substantia nigra lesions can be decreased by adrenal medulla grafts adjacent to the denervated striatum. Perhaps these grafts secrete dopamine that diffuses into the striatum. In the present study, we measured concentrations of catecholamines in adrenal medulla grafts as compared with the normal adrenal medulla. The grafts were found to have high but extremely variable concentrations of dopamine. In hosts with substantia nigra lesions, concentrations of dopamine in the adrenal medulla grafts were decreased. Substantia nigra lesions, however, tended to increase concentrations of epinephrine in the grafts, while norepinephrine and total catecholamine concentrations were not significantly affected. It is concluded that at least some adrenal medulla grafts contain concentrations of dopamine sufficient to account for their behavioral effects.

Adrenal Medulla↗

Presence, distribution and pharmacology of conjugated catecholamines in the rat spinal cord.

A method is described for the assay of conjugated catecholamines in the brain and spinal cord. Employing this method, the distribution of conjugated norepinephrine (NE) and dopamine (DA) was evaluated in the 5 main regions of the rat spinal cord and compared with those in the hypothalamus. In the spinal cord 26-35% of total catecholamines are conjugated. The percent of NE conjugated in the hypothalamus NE is about 17%, while that of DA is around 12%. Acute treatments with amphetamine, desmethylimipramine and haloperidol failed to change the concentrations of both total and conjugated NE and DA in the cervical spinal cord. Only amphetamine increased hypothalamic conjugated NE. It is concluded that evaluation of central conjugated catecholamines may provide an additional dimension to our ability to critically assess the mechanisms of action of drugs on central catecholamines.

Animals↗

Effects of antidepressant treatments on dopamine turnover in depressed patients.

Effects of five antidepressant treatments--clorgyline, desipramine hydrochloride, electroconvulsive treatment, lithium carbonate, and zimelidine hydrochloride--on urinary outputs of dopamine, dihydroxyphenylacetic acid, and homovanillic acid (HVA) were investigated in unipolar and bipolar depressed patients. Clorgyline and lithium carbonate, which stabilized mood in bipolar patients, reduced the urinary output of HVA and whole-body dopamine turnover. Electroconvulsive treatment and zimelidine were without major effects, whereas desipramine had variable effects on these indexes of dopamine metabolism. Three patients, two receiving desipramine and one receiving clorgyline, who had increased HVA output during the drug treatments, became severely agitated and delusional.

3,4-Dihydroxyphenylacetic Acid↗

Electroconvulsive treatment and lithium carbonate. Their effects on norepinephrine metabolism in patients with primary, major depressions.

Effects of electroconvulsive treatment (ECT) and lithium carbonate on norepinephrine metabolism were investigated in eight patients with primary, major depressions. A series of 12 ECTs reduced urinary norepinephrine and normetanephrine output significantly, and showed a tendency to reduce urinary vanillylmandelic acid output as well as whole-body norepinephrine turnover. Treatment with lithium carbonate significantly reduced urinary norepinephrine, normetanephrine, 3-methoxy-4-hydroxyphenylglycol, and vanillylmandelic acid output as well as whole-body norepinephrine turnover. These findings point to a common effect of antidepressant treatments since they are similar to results produced by administration of three other types of antidepressant drugs: clorgiline, a specific monoamine oxidase A inhibitor; desipramine, a relatively specific norepinephrine reuptake Inhibitor; and zimelidine, a relatively specific serotonin reuptake Inhibitor. These drugs reduce total production of norepinephrine and/or its major metabolites in depressed patients. Thus, five antidepressant treatments with different mechanisms of action have a common overall effect on the system.

Brompheniramine↗

Plasma and cerebrospinal fluid concentration of phenylacetic acid in humans and monkeys.

A rapid and reliable mass-fragmentographic method for assay of plasma and cerebrospinal fluid (CSF) concentrations of free and conjugated phenylacetic acid (PAA) is described. The method is used to compare plasma and CSF concentrations of PAA in humans and monkeys. Both packed and capillary columns are used. In humans approximately 45% of total plasma PAA is conjugated in contrast to approximately 60% in monkeys. Both free and conjugated PAA concentrations tend to be higher in monkeys than in humans. Plasma mean concentration of total PAA in humans and monkeys are, respectively, 459.1 and 838 ng/ml. Approximately 55 and 25% of total PAA in the CSF are conjugated in humans and monkeys, respectively. Total PAA mean concentrations in human and monkey CSF are 41.6 and 84.2 ng/ml. Because over 90% of total urine PAA in humans is conjugated, it is concluded that over 50% of urine phenylacetylglutamine may be derived from kidney conjugation of free plasma PAA and/or from the kidney's preferential filtration of conjugated PAA as contrasted with free PAA.

Animals↗

Effect of theophylline on neurotransmitters in preterm infants with apnea.

Urinary excretion of various catecholamine metabolites (4-hydroxy-3-methoxymandelic acid, homovanillic acid, 3-methoxy-4-hydroxphenylglycol) was studied in preterm infants with idiopathic apnea treated with theophylline. Relief of apnea in these infants was not associated with significant increase in the urinary excretion of various metabolites. We suggest that theophylline does not seem to relieve apnea of prematurity by the stimulation of peripheral catecholamine systems.

Apnea↗

Biochemical and pharmacological characteristics of conjugated catecholamines in the rat brain.

Mass-fragmentographic methods are described that enable the simultaneous measurement of total, free, and conjugated catecholamines in brain tissues. These methods were used to assess the distribution, kinetics, and pharmacological characteristics of total, free, and conjugated catecholamines in the hypothalamus, caudate nucleus, hippocampus, and septum. Conjugated norepinephrine (NE) represents approximately 20% of total NE in the hypothalamus, septum, and hippocampus, whereas the percentage is approximately 50% in the caudate nucleus. The percentages of conjugated dopamine (DA) in these brain areas are consistently less than those of NE (approximately 13%). Although in the hypothalamus the steady-state concentrations of total, free, and conjugated NE are over four times higher than those of the corresponding total, free, and conjugated DA, the turnover rates of this DA are comparable with those of the corresponding NE. Further, the ratios of conjugated NE or DA turnover rates to those of the total amines are higher than the corresponding ratios of their steady-state concentrations. Treatments with pargyline (75 mg/kg, i.p.; rats killed 30 and 60 min later) failed to change the contents of conjugated catecholamines in the hypothalamus and the caudate nucleus significantly. Pharmacological manipulation with a number of prototypic drugs revealed that although the assay of conjugated catecholamines might shed additional light on the effects of drugs on central catecholamines, the assessment of total or free amines are on the whole equally informative. In conclusion, a detailed assessment of brain conjugated catecholamines is reported. The information provided, fills a gap in our knowledge that has up to now not been adequately addressed.

Animals↗

Cerebrospinal fluid concentration of biogenic amine metabolites in idiopathic apnea of prematurity.

The concentration of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major metabolites of dopamine and norepinephrine, respectively, were studied in the cerebrospinal fluid (CSF) of 34 newborn infants. No significant difference was found in the levels of MHPG and homovanillic acid between preterm and term infants. Apneic preterm infants had significantly higher levels of MHPG than nonapneic prematures. Theophylline did not change the levels of these metabolites in CSF. There was a progressive rise of MHPG levels in CSF in preterm infants as their postnatal age increased. We suggest that idiopathic apnea of prematurity is not associated with depletion of catecholamine stores in the central nervous system. Theophylline does not seem to relieve apnea by stimulation of the central adrenergic system.

Apnea↗

Reliability of urinary monoamine and metabolite output measurements in depressed patients.

The authors measured urinary monoamines and their metabolite outputs in 12 unmedicated depressed patients. Output of 3-methoxy-4-hydroxy-phenylglycol and vanillylmandelic acid proved to be relatively stable from one sample to another. An average of at least two measures provided data with a meaningful reliability for normetanephrine, serotonin, and homovanillic acid output. Output of dopamine, norepinephrine, 5-hydroxyindoleacetic acid, and phenylethylamine was highly variable over time.

Depressive Disorder↗

Dopamine-containing small intensely fluorescent cells and sympathetic ganglion function.

This article reviews some of the neuropharmacology of the dopamine (DA)-containing small intensely fluorescent cells of sympathetic ganglia. The major metabolite of DA found in the ganglia is 3,4-dihydroxyphenylacetic acid (DOPAC). DOPAC content appears to be a direct reflection of DA synthesis. DA synthesis can be enhanced by muscarinic agonists and diminished by muscarinic antagonists. Neuroleptic drugs stimulate DA synthesis in the ganglion, which suggests that a local negative neuronal feedback loop might operate within the ganglion. There may be a correlation between deficient DA synthesis in spontaneous hypertensive rats and the development of hypertension. It is possible that some of the peripheral side effects of drugs that act on dopaminergic neurons in the brain might originate from the drugs' action on peripheral dopaminergic neuronal systems such as the sympathetic ganglion.

3,4-Dihydroxyphenylacetic Acid↗

Platelet monoamine oxidase activity and plasma levels of non-catecholic phenylethylamines in insulin-dependent diabetic subjects.

The activity of blood platelets monoamine oxidase (MAO) was significantly reduced in a group of insulin-dependent diabetics when compared to sex- and age-matched controls. This enzymatic change was accompanied by a dramatic increase in the plasma levels of phenylethylamine, whereas no significant changes were observed for the concentration of either p-tyramine or phenylethanolamine. Levels of the o- and m-isomers of tyramine were below detectable limits (less than 0.050 ng/ml). A possible role of the MAO/monoamine system in the pathophysiology of diabetes is discussed.

Blood Platelets↗

Different effects of behaviorally equipotent doses of amphetamine and methamphetamine on brain biogenic amines: specific increase of phenylethylamine by amphetamine.

The effects of acute semichronic (twice daily for three days) treatments with the same doses of amphetamine (AMPH) and methamphetamine (M-AMPH) on rat brain phenylethylamine (PEA) and catecholamines were evaluated. These treatments produced similar behavioral responses and hence are assumed to be generally equipotent. Both drugs entered the brain rapidly but at different rates. While AMPH and M-AMPH produced comparable changes in the contents of catecholamines and their metabolites in the hypothalamus and caudate nucleus, only AMPH significantly elevated PEA. The elevated brain PEA produced by AMPH was not due to alpha-demethylation of AMPH. It is concluded that brain PEA may mediate some of AMPH behavioral effects but not those of M-AMPH. The catecholamines appear to be involved in the effects of both drugs.

Amphetamine↗