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Biomedical subjects

G Dordain

Publications and source records attributed to G Dordain.

At least 19 recordsLinked to original sources
PubMed1994

Apomorphine and diphasic dyskinesia.

We report on three observations of parkinsonian patients with levo-dopa-induced diphasic dyskinesias, who received subcutaneous apomorphine to reduce the duration of abnormal movements. Apomorphine was effective in reducing the duration of diphasic dyskinesias at doses higher than the threshold doses necessary to induce an "on" phase (mean increase: 43%). However, after a few months of treatment, apomorphine was ineffective in stopping abnormal movements, even when doses were increased. In two patients, apomorphine remained effective in the morning, but increased the intensity of the dyskinesias in the afternoon. Acute diurnal variations of the pharmacodynamic striatal response are suggested explanation for these clinical observations.

Aged↗
PubMed1993

[Demyelinating involvement in Borrelian neuropathies].

Five patients (4 men, 1 woman, aged 51-67), were hospitalized for peripheral painful neuropathies. The serological survey and the dramatic responses to penicillin confirmed the responsibility of Borrelia burgdorferi in all 5 cases. Electromyographical studies showed evidence of demyelination: prolonged distal latency, slowing down of nerve conduction velocity. In 3 patients this pattern was related to axonal degeneration as shown by fibrillation potentials and reduced voluntary motor unit potentials recorded on needle examination. The other two showed no axonal degeneration. One also had motor conduction blocks. Such a demyelination could be due to vasculitis of the vasa nervorum described in tick-bone meningoradiculitis.

Aged↗
PubMed1993

Dopamine-derived tetrahydroisoquinolines and Parkinson's disease.

The daily urinary excretion of salsolinol, 1,2-dehydrosalsolinol, and norsalsolinol, as free, glucuronide, and sulfate, has been measured in parkinsonian patients and age-matched controls in an attempt to examine whether the determination of dopamine-derived alkaloids in urine may be used as a marker of the decrease in brain dopamine levels associated with the disease. In contrast with a preliminary study where the daily urinary excretion of total salsolinol was significantly higher in young controls than in parkinsonians, in the present study no difference was found between parkinsonian patients and controls concerning salsolinol and norsalsolinol excretion. However, the urinary excretion of total 1,2-dehydrosalsolinol was significantly higher in the control group, owing to a statistically significant increase in its excretion as sulfate in this group. Further studies appear to be necessary to establish whether 1,2-dehydrosalsolinol, salsolinol, and/or any other dopamine-derived alkaloid may serve for the detection of subjects with dysfunctions of the dopaminergic system.

Aged↗
PubMed1992

Antinociceptive activity of metapramine in mice. Relationship with its pharmacokinetic properties.

The antinociceptive effect of acutely and chronically (every brain elimination half-life time) administered metapramine, a tricyclic antidepressant without anticholinergic or cardiotoxic effects, was studied in three different pain tests. In the hot plate test, its action was more potent when jumping was used as a pain parameter (acute ED50 = 19 +/- 3 mg/kg, i.p.) than when pain was assessed by licking of forepaws (only 20 mg/kg, i.p. was weakly active). Five chronic doses of 15 mg/kg were as active in the tail-flick test as an acute dose of 20 mg/kg (only active dose). Metapramine was more effective in the PBQ-induced writhing test after acute (ED50 = 9.9 +/- 0.1 mg/kg, i.p.) and chronic administration. A significant linear correlation was found between the effect in this test and plasma and overall brain levels of metapramine. No correlation was observed with levels of its three desmethylated metabolites. The usefullness of using a well-defined pattern of administration based on pharmacokinetic parameters and the involvement of monoaminergic mechanisms and of some metabolites of metapramine are discussed.

Animals↗
PubMed1991

Urinary elimination of salsolinol enantiomers in alcoholics.

The analysis of the urine from 6 chronic alcoholics showed that (R)- and (S)-salsolinol were detectable in 4 subjects, the R enantiomer was only found in one and that both enantiomers were under the limit of detection in another one. 1,2-Dehydrosalsolinol was present in the urine of all of them. There was no correlation between the presence of alcohol in blood upon admission to the hospital and that of either salsolinol enantiomer in urine In a previous study (Strolin Benedetti et al., 1989 b), both salsolinol enantiomers were found in the urine of 3 out of 6 healthy subjects, possibly in relation with regular intake of alcoholic beverages. The content in (R)- and (S)-salsolinol was determined in the same 3 subjects after deprivation of alcohol for 24 h. Under these conditions, only (R)-salsolinol was detected in urine and this also after ingestion of 50 g of alcohol (500 ml Chianti). The possible involvement of the non-physiological enantiomer of salsolinol in alcohol addiction deserves further study.

Adult↗
PubMed1990

[The elderly and psychotropic drugs].

The incidence of adverse reactions to drugs is two or three times greater in elderly people than in adults. Elderly people are great consumers of psychotropic drugs which are most often responsible for these reactions, the chief culprits being anticholinergics and neuroleptics. These drugs must be avoided at that age, but neuroleptics may be justified in some circumstances, such as uncontrollable excitement or delusions. The dysautonomia associated with ageing induces functional disorders that are similar to those induced by psychotropic drugs, so that the responsibility of these drugs is frequently under-evaluated. In those rare cases where psychotropic agents are mandatory, only one of them must be prescribed in low doses and, whenever possible, for a limited period.

Aged↗
PubMed1990

Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects.

The R enantiomer of salsolinol was detected in the urine of two out of six healthy subjects, whereas 1,2-dehydrosalsolinol was present in the urine of all the subjects. (S)-salsolinol was never detected. Administration of Madopar for 7 days resulted in the presence of large amounts of (R)- and (S)-salsolinol in the urine of five out of the six subjects, the urinary excretion of 1,2-dehydrosalsolinol being generally not markedly increased. The presence of 1,2-dehydrosalsolinol in urine suggests that the biosynthesis of salsolinol in healthy volunteers should occur by condensation of dopamine with pyruvic acid, in keeping with Hahn's hypothesis. The absence of salsolinol in the urine of one subject after Madopar administration seems to indicate that the biological system(s) involved in the reduction of the C = N bond in 1,2-dehydrosalsolinol can be missing or not, or poorly, functional in some individuals, and suggests that there is no alternative pathway for the formation of salsolinol in healthy volunteers.

Adult↗
PubMed1989

Enantiomeric composition of urinary salsolinol in parkinsonian patients after Madopar.

Urinary salsolinol output had been shown to be lower in Parkinsonian patients than in controls and to increase largely after L-dopa therapy. It had also been established that the R enantiomer of salsolinol is either the predominant or the sole enantiomer present in the urine of healthy subjects. When Madopar was administered to Parkinsonians, the enantiomeric composition of urinary salsolinol showed an S/R ratio around 1. Considering brain and plasma concentrations in dopamine, acetaldehyde and pyruvate, it is suggested that, under physiological conditions, urinary salsolinol should have a central origin in humans. Conversely, urinary salsolinol in Madopar-treated Parkinsonian patients might be predominantly formed at the periphery.

Aged↗
PubMed1989

Antinociceptive activity of salsolinol (racemate, R(+)-, S(-)-enantiomers): evidence of a peripheral mechanism.

The existence and the characteristics of the antinociceptive action of salsolinol (racemate) and its two R(+)- and S(-)-enantiomers were studied using different pain tests in mice. None of these drugs possessed a significant activity on the tests sensitive to central acting analgesics (hot-plate and tail-flick tests), either after systemic (i.p.) or central (i.c.v.) injections. However, injected i.p., they reduced the number of writhes induced by phenylbenzoquinone; the ED50 was 79 +/- 2, 73 +/- 2 and 61 +/- 2 mg/kg for racemate, R(+)- and S(-)-enantiomer respectively. This activity was not antagonized by naloxone. Moreover, racemate and S(-) reduced, only for the highest used active dose on the PBQ test (128 mg/kg, i.p.), the edema induced by an intraplantar injection of carrageenin. These results provide evidence of an analgesic activity independent of the endogenous opiate systems and involving a peripheral mechanism.

Analgesia↗
PubMed1989

Pharmacokinetics of metapramine and its demethylated metabolites in plasma and brain of mice.

Previous studies on pharmacokinetic parameters of tricyclic antidepressants (TCAs) in rodents have shown different results from those obtained for the same drugs in man. The kinetics of metapramine (META) and its major demethylated metabolites (METs) were studied in the SWISS CD 1 mouse after acute administration in order to establish the pharmacokinetic parameters in plasma and brain. The plasma half-life (T1/2) was very short (87 min) compared with the half-life (7 h) in man. The metabolism of META was intensive as was the transfer of META and its metabolites into the brain. The kinetic profiles of the substances were quite similar both in plasma and in brain, namely a bicompartment open model. META was rapidly absorbed (Tmax = 10 min) into and quickly eliminated (T 1/2 = 40 min) from the brain. These parameters were used to schedule sampling (blood and brain) at the appropriate time after acute administration of increased doses. The administered doses were significantly correlated to firstly the plasma or brain levels of META, secondly the plasma levels of the main monodemethylated metabolite (MET I), and thirdly the plasma or brain levels of META + METs. Finally, the evolution of plasma and brain levels of the substances was studied after repeated injections (i.e. every 40 min) and confirmed the high affinity of META and its metabolites for the brain regions.

Animals↗
PubMed1989

Walk headache: an unusual manifestation of ischemic heart disease.

A 71 year old man sought neurological advice because for two years he had suffered from headache every time he made an effort. A treadmill stress test showed a relation between effort, headache and depression of ST segments on E.C.G. With isosorbide dinitrate and diltiazem, the manifestations improved. This suggests a referred head pain due to myocardial ischemia.

Aged↗
PubMed1988

Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases.

Tetrahydroisoquinoline (TIQ) alkaloids and 1-carboxy TIQ derivatives have been found in human fluids and/or tissues. The possible biosynthetic pathways of salsolinol (Sal), taken as an example of TIQs, are discussed, and the possibility that biosynthesis occurs through a stereospecific enzymatic reaction is considered. In this respect, it is reported that the R enantiomer of Sal predominates in urines of healthy volunteers, whereas the S enantiomer predominates in port wine and possibly in other beverages and foods, suggesting that Sal present in humans could have, at least partially, and endogenous enzymatic origin. TIQs and other dopamine-derived alkaloids are weak MAO inhibitors, the R enantiomer of Sal and salsolidine being more potent than the S form. The changes in monoamine oxidase activity and the nigrostriatal concentrations of dopamine and homovanillic acid in Parkinson's and Huntington's diseases and in alcoholism are reviewed. In these pathological situations, changes in the levels of dopamine-derived alkaloid levels may occur. The possibility that the modifications found might cause or contribute to changes in mental and/or neurophysiological states in these pathological situations is considered.

Alcoholism↗