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Biomedical subjects

F Karoum

Publications and source records attributed to F Karoum.

152 records · Page 9Linked to original sources
PubMed1969

m-Hydroxyphenylacetic acid formation from L-dopa in man: suppression by neomycin.

The increased excretion of m-hydroxyphenylacetic acid in the urine of patients with parkinsonism being treated with L-dopa was reduced by gut sterilization with neomycin. The p-de-hydroxylation step is thus brought about solely by the action of gut flora; the pathway is unlikely to be involved in the events within the brain leading to the therapeutic benefit effected by L-dopa.

Dihydroxyphenylalanine↗
PubMed1969

The metabolism of orally administered L-Dopa in Parkinsonism.

1. Gas-liquid chromatographic methods were used to measure urinary acidic and alcoholic metabolites of L-DOPA, which had been administered in high oral dosage to patients with postencephalitic and idiopathic Parkinsonism.2. The output of these compounds was normal before treatment. During drug therapy, large quantities of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were excreted but traces only of 4-hydroxy-3-methoxyphenylethanol. Noradrenaline metabolites showed little change in output other than a small increase in 4-hydroxy-3-methoxymandelic acid.3. Information was obtained about a number of minor routes of degradation which might be implicated in the therapeutic action of L-DOPA. A raised output of m-hydroxyphenylacetic acid pointed to p-dehydroxylation of dihydroxyphenylacetic acid by gut flora. Evidence of transamination as a minor metabolic pathway was obtained by finding appreciable urinary levels of 4-hydroxy-3-methoxyphenyllactic acid. A keto-acid precursor of this compound may act as competitive inhibitor of an enzyme active in the normal degradation route of tyrosine, p-hydroxyphenylpyruvic acid oxidase, for increased amounts of p-hydroxyphenyllactic acid, the major metabolic derivative of p-hydroxyphenylpyruvic acid, accumulated in the urine during DOPA treatment.

Chromatography, Gas↗
PubMedDate not supplied

Alterations in dopamine metabolism by intraperitoneal ethanol in rats selected for high and low ethanol preference: a 3-methoxytyramine study.

Effects of an ethanol dose (1 g/kg, IP) on the metabolism of dopamine (DA) in the nucleus accumbens, striatum and hypothalamus of ethanol-naive alcohol-preferring (AA) and alcohol-avoiding (ANA) rats were studied. Rats were sacrificed by focused-beam microwave irradiation of the brain 20 minutes after ethanol administration, and the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), assumed to reflect DA metabolism, and of 3-methoxytyramine (3-MT), assumed to reflect DA release, were measured using gas chromatography-mass spectrometry. Basal striatal DOPAC and HVA concentrations were higher in the AA rats in comparison with ANA rats. Ethanol increased HVA, but not DOPAC, concentration in the nucleus accumbens and striatum, but not in the hypothalamus. There was a significant rat line x ethanol treatment interaction with respect to HVA concentration in the nucleus accumbens. The increase in HVA was higher in the AA than ANA rats. Basal 3-MT concentration was not changed by ethanol, except in the nucleus accumbens, where a significant rat line x ethanol treatment interaction was found. A decrease in 3-MT concentration was only detected in the ANA rats. After inhibition of monoamine oxidase with pargyline hydrochloride (75 mg/kg, IP, 10 min before sacrifice), 3-MT accumulation was decreased by ethanol, especially in the nucleus accumbens of both AA and ANA rat lines as well as in that of nonselected Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Effects of the administration of amphetamine, either alone or in combination with reserpine or cocaine, on regional brain beta-phenylethylamine and dopamine release.

The effect of amphetamine sulfate (AMPH) on beta-phenylethylamine (PEA) and 3-methoxytyramine (3MT) levels in the rat frontal and cingulate cortices, the nucleus accumbens, and the striatum were evaluated after the administration of either cocaine or reserpine alone and in combination with AMPH. The purpose of this study was to evaluate the neuromodulator properties of PEA on dopamine (DA) release as reflected by 3MT steady-state concentrations. The highest concentration of PEA was found in the nucleus accumbens, followed by the cingulate and frontal cortices, and then the striatum. Time-course effects of the intraperitoneal administration of 5 mg/kg AMPH on PEA and 3MT concentrations were similar but not identical. AMPH at a dosage of 1 mg/kg significantly increased PEA concentration only in the striatum. A dosage of 2.5 mg/kg reserpine, which markedly depressed 3MT levels in all brain regions studied except the striatum, significantly reduced PEA concentrations only in the nucleus accumbens. This dosage of reserpine reduced DA concentrations by more than 80% in all regions examined, but its effects on norepinephrine were less marked. Pretreatment with cocaine (10 mg/kg) or reserpine (2.5 mg/kg) potentiated the effects of 1 mg/kg AMPH on PEA and 3MT levels in the frontal cortex and of 3MT in the striatum. Pretreatment with either 1 mg/kg reserpine (specifically used to partially mobilize DA storage) or cocaine (10 mg/kg) produced quantitative changes in the effects of 5 mg/kg AMPH on PEA and 3MT levels that were region-specific. For example, in contrast to the cortical regions and the nucleus accumbens, the AMPH-induced increase in 3MT was potentiated in the striatum. On the other hand, the increase in brain PEA produced by AMPH (5 mg/kg) was not influenced by either increased cytoplasmic DA (as deduced from the effects of 1 mg/kg reserpine pretreatment) or DA uptake inhibition (as deduced from the effect of cocaine pretreatment) in the frontal cortex or the nucleus accumbens. Furthermore, the increase in PEA produced by AMPH (5 mg/kg) in the cingulate cortex and the striatum were abolished and potentiated, respectively, by these drug pretreatments. Our results suggest that although DA release and PEA formation are stimulated by AMPH, these effects appear to involve mechanisms that are not directly related and hence suggest a dissociation between 3MT and PEA formation in the brain. Our work also suggests that PEA is most likely not to be co-released with DA following the administration of AMPH. Therefore, it is concluded that whatever physiological role PEA may play in central synaptic transmission, its effects do not appear to be dependent on DA release.

Amphetamine↗