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N Moore

Publications and source records attributed to N Moore.

At least 127 records · Page 7Linked to original sources

Application of an analytical method to calcium acetylhomotaurinate determination in urine.

After urine purification, plasma and urine concentrations of calcium acetylhomotaurinate (Acamprosate, CaAOTA) were determined with a high-performance liquid chromatography method following i.v. administration of the drug in two dogs. Results obtained in serum were in good agreement with those found previously. The CaAOTA urine determination is a promising method to be used in healthy volunteers.

Acamprosate↗

[Interactions of antitubercular drugs].

Antituberculous drugs are never used alone but are often given concomitantly with drugs prescribed for other diseases. We have therefore reviewed the potential interactions of antituberculous drugs between themselves and with other drugs. Rifampicin being a potent enzyme inducer will decrease the plasma levels of a wide range of drugs. This in turn will decrease the effectiveness of these drugs if they are unmetabolized and active, or increase drug toxicity if the metabolites are toxic. Within the first category are the oral contraceptives, steroids, oral antidiabetics, oral anticoagulants and digitalis. Within the second category is thought to be isoniazid on account of its hepatotoxicity. In contrast, isoniazid (INH) is an enzyme inhibitor. Drugs with hepatic metabolism will tend to accumulate, although this seems clinically relevant only with antiepileptic drugs, diazepam, triazolam and oral anticoagulants (with high INH doses). Many other cases of drug interaction have been described, but they seem to be rare and may not be clinically relevant. INH and rifampicin do not seem to modify each other's metabolism consistently, but it may be wise to check the serum INH levels during coadministration. As said above, rifampicin does increase the hepatotoxicity of INH. INH also inhibits monoamine oxidase and will interact with other MAOI, as well as with fish, cheese or wine with high histamine or tyramine contents. The only interaction found with ethambutol is with diazepam: it increases its clearance and free fraction. Obviously, streptomycin potentiates the ototoxicity of other amino-glycosides, such as capreomycin, kanamycin or viomycin, so that combining them is strictly contra-indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗

Physicochemical, pharmacological and pharmacokinetic study of a new GABAergic compound, calcium acetylhomotaurinate.

It has been shown that calcium acetylhomotaurinate (Ca AOTA; Meram Patent, France) decreased voluntary ethanol intake in rats (1); this was antagonized by bicuculline. Homotaurine did not have this effect. We thought this was due to a different blood-brain barrier crossing ability for the two drugs. The present study was, therefore, planned to confirm blood-barrier crossing by Ca AOTA and to study the drug's physicochemical and pharmacokinetic characteristics. Both in vitro and in vivo (i.p.) administration of Ca AOTA increased the accumulation of [3H] GABA in rat striatal synaptosomal preparations. The chemical study confirmed Ca AOTA's great stability in biological and hydrophilic media, excluding a "homotaurine-dispensing" effect. The molecule was totally dissociated in such media, but the absence of any detectable acid form at any pH indicates that ion pairs are formed to cross barriers, and/or that a carrier system is used. The pharmacokinetic study showed short half-lives (5 and 30 min for the distribution and elimination phases) and small distribution volumes. However, the elimination phase distribution volume was dose-dependent, a further argument for a carrier transport system. From the present study it appears that Ca AOTA is an extremely stable drug, totally dissociated in hydrophilic media, which acts centrally as a GABA agonist after crossing the blood-brain barrier. It is not a precursor of homotaurine and presumably crosses barriers with the help of a transporter.

Acamprosate↗

Circling behaviour in rats with unilateral lesions of the nigrostriatum induced by 6-hydroxydopamine: changes induced by oral administration of cytidine-5'-diphosphocholine.

A unilateral administration of 6-hydroxydopamine into the nigrostriatal system of the rat was responsible for ipsiversive circling behaviour in response to administration and, in time, of contraversive circling behaviour in response to L-DOPA and apomorphine. This contraversive circling behaviour appears to be mediated by the development, on the lesioned side, of supersensitivity of postsynaptic dopamine receptors. Subchronic treatment with cytidine-5'-diphosphocholine (p.o.) by itself was devoid of behavioural effects. The CDP-choline did not modify the apomorphine-induced stimulant effect but potentiated the circling behaviour produced by L-DOPA and amphetamine. The data show that the effects of CDP-choline were mediated by a presynaptic mechanism: the potentiation of the effects of L-DOPA cannot be explained by an activation of tyrosine hydroxylase, but seems to be related to an improvement of release of newly synthesized dopamine from exogenous L-DOPA.

Administration, Oral↗

A controlled clinical trial of tiaspirone in schizophrenia.

The antipsychotic efficacy of tiaspirone, a new atypical antipsychotic agent, was compared to standard neuroleptics, in a single-blind cross-over study. Nine actively psychotic schizophrenic patients entered the study and 6 completed it. Significant overall improvement, on BPRS and CGI ratings, occurred by week 4, on both--tiaspirone and standard neuroleptics. There were no significant differences between tiaspirone and standard neuroleptics, in their antipsychotic efficacy. In keeping with the preclinical profile of tiaspirone, no extrapyramidal symptoms (EPS) were observed with tiaspirone. Two patients showed EPS on standard neuroleptics. Five of the 6 patients showed mild transient elevation of liver enzymes while on tiaspirone. Liver enzymes returned to normal within 3 weeks of discontinuation of tiaspirone. Tiaspirone appears to be a promising new antipsychotic agent that may be clinically effective without causing extrapyramidal syndromes.

Adult↗

Peripheral neuropathies during hypoxaemic chronic obstructive airways disease.

Peripheral nervous system alterations during chronic obstructive airways disease (COAD) with respiratory insufficiency seem more frequent than usual neurological practice would suggest. Almost a third of COAD patients have clinical evidence of peripheral neuropathy and two thirds have electrophysiological abnormalities. The presentation consists of a polyneuropathy often subclinical or with predominantly sensory signs, which has the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke (which contains at least three neurotoxic constituents) alcoholism, malnutrition and adverse effects of certain drugs. Hypoxia probably plays the leading part, either by direct action on nerves fibres or by enhancing the effects of other neurotoxic factors or deficiencies.

Alcohol Drinking↗

Evolution of peripheral nerve function in hypoxaemic COPD patients taking almitrine bismesylate: a prospective long-term study.

Almitrine bismesylate has been thought to provoke peripheral neuropathies in patients with chronic obstructive pulmonary disease (COPD). However, there seems to exist alterations of peripheral nerve function in patients with COPD, who have not taken almitrine. We have therefore examined 22 patients with COPD and no other cause of peripheral neuropathy (PN), before and after 6 and 12 months of treatment with almitrine (50 mg bd). Seventy-eight similar patients, who did not take almitrine, were also studied (controls). Sixty-four per cent of controls, and 55% of almitrine patients initially had at least one neurophysiological abnormality. There was no change in the studied parameters after 6 months and one year's treatment with almitrine.

Aged↗

Noradrenaline and GABA brain receptors are co-involved in the voluntary intake of ethanol by rats.

Stimulation of GABA brain receptors by calcium bis acetyl-homotaurine (a new GABAergic agent) or of noradrenergic brain receptors by metapramine reduces the voluntary intake of ethanol by rats. Bicuculline antagonizes the effects of both drugs. It is suggested that both GABA and noradrenaline are implicated in ethanol intake, and that there is a common final pathway of the two systems to modulate ethanol intake.

Acamprosate↗

Platelet affinity for serotonin is increased in alcoholics and former alcoholics: a biological marker for dependence?

The kinetics of 3H serotonin platelet uptake were studied in alcoholics and former alcoholics to see whether differences found between alcohol-preferring and non-preferring rats could be reproduced in man. Three groups of patients were studied: 10 dependent alcoholics on admission for treatment; 10 dependent alcoholics after 20 days of treatment; 8 former dependent alcoholics, abstinent for 1-11 years. Controls were non-alcoholics, matched for age and sex. The Km for 3H serotonin uptake in platelets was lower in patients from all three groups compared to 15 controls. This phenomenon could be congenital or induced by the previous excessive intake of alcohol. We believe that this increased platelet affinity for serotonin, in the absence of cirrhosis of the liver and/or depression could be a marker for alcohol dependence, enabling the therapeutic effort to be focussed on these patients.

Adult↗

Circling behavior in normoxic or hypoxic rats with unilateral 6-OHDA nigrostriatal lesion. Part 1. Effects of apomorphine and L-dopa.

Unilateral administration of 6-hydroxydopamine (6-OHDA) into the rat nigrostriatal system provokes circling behavior in response to apomorphine and L-dopa. This behavior appears to be mediated by the development in the lesioned side of a postsynaptic dopamine receptors supersensitivity. Acute hypobaric hypoxia does not modify the apomorphine-induced stimulant effects, but does oppose the L-dopa-induced circling behavior. Our data suggest that effects of hypoxia are mediated by a presynaptic mechanism. The antagonism of the effects of L-dopa cannot be explained by the inhibition of activity of the oxygen-dependent enzyme tyrosine hydroxylase, but seems to be related to an impairment of the release of newly synthesized dopamine from exogenous L-dopa.

Animals↗

Circling in normoxic or hypoxic rats with unilateral 6-OHDA nigrostriatal lesion. Part 2. Effects of d-amphetamine.

Unilateral administration of 6-hydroxydopamine into the rat nigrostriatal system induces a unilateral damage of the dopamine (DA) containing neurons. In such lesioned animals, d-amphetamine (AMPH) induces circling behavior (ipsiversive circling) in relation to its DA releasing property in the non-lesioned side. A preexposition to hypoxia potentiates the behavioral effect of AMPH: this can be related to an increase in the amount of substrate available for release, dopamine. Hypoxia occurring just after the administration of AMPH does not initially modify the AMPH induced circling behavior. This suggests that tyrosine hydroxylase inhibition by hypoxia is not a limiting factor of the releasing effect of AMPH. After 20 min of hypoxia, circling decreases. This impairment could be mediated by a decrease of the amount of available DA and/or by a decrease of release.

Animals↗

[Pharmacokinetics and pharmacodynamic effects of digoxin in dilated cardiomyopathies. Influence of nicardipine].

Numerous studies have been devoted to the effect of slow calcium channel inhibitors on plasma digoxin concentrations. The principal drugs tested, verapamil and nifedipine, were found to increase significantly plasma digoxin levels mainly by reducing digoxin total clearance. Very few studies on the nicardipine-digoxin interaction have been reported. The dual purpose of the present study was to evaluate the influence of orally administered nicardipine on plasma digoxin concentrations over 24 hours and to measure possible variations in the pharmacodynamic effects of digoxin in 9 patients with chronic congestive heart failure. The pharmacodynamic assessment involved simple and cross-sectional echocardiography, systolic time interval measurements and cardiac catheterization. In these patients under chronic digoxin treatment, oral nicardipine had little effect on plasma digoxin concentrations which increased but not significantly; no sign of digitalis toxicity was observed. Nicardipine improved left ventricular function and myocardial contractility by reducing after-load, the nicardipine-induced peripheral vasodilatation tending to counteract the digoxin-induced vasoconstriction.

Aged↗

[Diffusion of vancomycin in the cerebrospinal fluid, in the dog, in the absence of meningeal inflammation].

The diffusion of vancomycin into the cerebro-spinal fluid was studied in 5 healthy dogs. Its appears that vancomycin does diffuse across the blood-brain barrier. Though the concentrations reached in the CSF are low, they are of the same order of magnitude as the minimal inhibitory concentrations of this antibiotic towards the germs usually treated. The usual pharmacokinetic parameters were determined.

Animals↗