Search PubMed⌕ Search

Biomedical subjects

G Dordain

Publications and source records attributed to G Dordain.

At least 37 records · Page 2Linked to original sources

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

Benzodiazepine withdrawal seizures: analysis of 48 case reports.

Various reactions to benzodiazepine withdrawal have been widely described. Among these, seizures have occasionally occurred on abrupt withdrawal. Our own experience of 48 cases of seizures suspected to have been caused by benzodiazepine withdrawal and reported to the Adverse Drug Reaction (ADR) Monitoring Center (1979-1985) showed that a great variety of benzodiazepines with different half-lives were involved, those most frequently implicated being the most widely prescribed. The occurrence of seizures was not always related to the interruption of long-term treatment (from a few days to greater than 7 years) nor to high-dose treatment, the range of dosages being usually close to that recommended. However, in some cases, several benzodiazepines had been taken simultaneously. The time between the last intake of the drug(s) and the occurrence of the seizures was shorter when a short-life benzodiazepine had been used. Additional factors were frequently involved; these factors were present in 29 cases and were multiple in nine of them. The incidence of withdrawal seizures was related more to the presence of these additional factors than to either the pharmacokinetics of the drugs or the pattern of treatment.

Adult↗

[Neurologic manifestations of basal cell nevomatosis. A case].

The naevoid basal cell syndrome, also called Gorlin's syndrome, is a dysembryoplasia akin to the phakomatoses and which may affect the skin, the bones, the nervous system, the eyes, the endocrine glands and the genitalia. A case with numerous tumours and malformations is presented, together with a review of the literature.

Aged↗

[Methodology for a controlled trial in Alzheimer's disease].

The various evaluation scales available to study the clinical courses of Alzheimer-like dementias are controverted, and the practical aspects of a controlled trial are being considered. A tentative protocol has been designed, in which multiple individual assessments are combined with several validated scales and tests. This protocol would lend itself to a multicentre study, as it only includes evaluation tools that are easy to handle and do not require too much time. It should make it possible to select a relatively homogeneous group of patients and provide an opportunity to quantify the course of Alzheimer's disease over one year. In the discussion, emphasis is laid upon the foreseeable difficulty to evaluate a therapeutic benefit in our present imperfect knowledge of the natural history and prognostic factors of the disease.

Aged↗

Psychopharmacological profile of salsolinol.

SAL is a tetraisoquinolein (T.I.Q.), resulting from the condensation of acetaldehyde and dopamine. SAL, injected intraperitoneally, is active in tests commonly used to screen potential antidepressants. This effect is especially studied by using antagonism of apomorphine, reserpine, oxotremorine-induced hypothermia. The noradrenergic system seems to be involved in the mechanism of action.

Animals↗