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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 235 records · Page 13Linked to original sources
PubMed1982

Caffeine disposition after oral doses.

Caffeine (TMX) disposition was studied in mean after 1, 5, and 10 mg/kg in water, as mocha coffee (1.54 mg/kg) and as a soft drink (0.22 mg/kg). TMX and its metabolites were analyzed in plasma and urine by high-pressure liquid chromatography. The design permitted confirmation of most of the partial results in various experimental settings and contributed new data on the metabolic disposition of TMX, with specific reference to main dimethylxanthine metabolite found in plasma, paraxanthine (1,7-dimethylxanthine). Different analysis methods were compared for the calculated parameters (absorption and elimination rate constants and renal clearance)to assess the consistency of results. The kinetics of TMX and of its dimethylated metabolites in plasma were described with a model that used an analogdigital hybrid computing system. In addition to providing a comprehensive profile of TMS disposition in the healthy adult, the results indicate tha TMX exhibits dose-independent kinetics at the levels at which man normally takes TMX.

Administration, Oral↗
PubMed1982

Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system.

Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25-30% was produced at the dose of 20 mg kg-1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.

Acetylcholine↗
PubMed1982

Walker carcinoma 256: a model for studies on tumor-induced anorexia and cachexia.

Data on anorexia and cachexia induced by Walker carcinoma 256 in Sprague-Dawley rats were analyzed in order to standardize an experimental model using a statistical (nondeterministical) procedure for assessing the efficacy of potential orexigenic agents. This model was characterized by a mean survival time of 14 +/- 1 days and by food intake and body weight loss starting from day 6 after tumor implantation. The complex course of cachexia was characterized by reduction in the weight of gastrocnemius muscle and epididymal adipose tissue, taken as representative sites of loss of proteins and lipids.

Adipose Tissue↗
PubMed1982

Notes on buspirone's mechanisms of action.

Buspirone is a novel psychotropic drug with clear anxiolytic activity in man. There are a number of neurochemical differences between buspirone and both neuroleptics and benzodiazepines. Moreover, buspirone is extensively metabolized, and several metabolites are present in the brain together with the parent compound. One of these, 1-PP, is present in the brain at higher concentrations than the parent drug, particularly when the drug is given orally. On the basis of the reported experimental data, it can be postulated that buspirone's anticonflict activity in rats may be mediated, at least partially, through 1-PP, without involving any effect on the dopaminergic system. The possibility that buspirone and 1-PP may mimic the action of benzodiazepine on some sites in the complex benzodiazepine-GABA receptors is discussed.

Acetylcholine↗
PubMed1982

D-L-tetrahydropalmatine as monoamine depletor.

D-L-Tetrahydropalmatine (THP), an alkaloid found in the plants of the Carydalis species, has been used as a non-narcotic analgesic and immediate or short-acting hypnotic. The drug's biochemical effects on the rat monoaminergic neuronal system were studied and the findings are presented here. THP's effects on concentrations of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were determined. In all cases the drug caused a depletion of these transmitters. DA was most markedly affected by treatment (-70%), followed by NA (-50%) and 5-HT (-30%). In parallel with the reduced concentrations of the transmitters there was an increase in their acid and neutral metabolites: HVA and DOPAC for DA, 5HIAA for 5-HT and MHPG-SO4 for NA, indicating that THP increases the release of the monoamines. The concentration of 3-methoxytyramine, an extraneuronal metabolite of DA, was, however, reduced suggesting that the observed increase in metabolism is only an intraneuronal phenomenon and that the release of the neutotransmitter is actually impaired. The effect of THP on the peripheral adrenergic system was also determined. NA stores in heart sympathetic nerves were depleted, but the drug had no effect on the adrenaline content of adrenal glands. The biochemical action of THP seems, therefore, to be similar to that of reserpine-like drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Activity of 1-p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt in M 5076/73A ovarian reticular cell sarcoma of the mouse.

1-p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt (DM-COOK) was tested on M 5076/73A (M5) mouse sarcoma at a dose of 40 or 50 mg/kg/day (Days 6--14) after im transplant of 7 x 10(5) cells, with or without surgical removal of the primary tumor on Day 14. Treatment at either dose level resulted in reduction of the primary tumor weight to around 50% of that in the controls, and striking antimetastatic effects were observed. When a dose of 40 or 50 mg/kg of DM-COOK was followed by surgery, there were 14% and 40% long-term survivors, respectively, but the higher dose caused about 30% toxic deaths. After iv injection of 10(3) or 10(5) M5 tumor cells, no artificial metastases appeared in DM-COOK-treated mice, whereas all control animals had metastatic involvement in the liver, spleen, ovaries, and kidneys.

Animals↗
PubMed1982

Hexamethylmelamine distribution in patients with ovarian and other pelvic cancers.

The distribution of hexamethylmelamine (HMM) was investigated in surgical biopsies from 12 patients with pelvic cancer who were given an oral dose of 200 mg at 2-24 hours before the operation. The highest concentrations of HMM were found in tissues, such as omentum and subcutaneous tissue, that have a predominant lipidic component. HMM concentrations in the primary tumor were lower than in other tissues and were similar to those in plasma. HMM concentrations in metastases appeared to be higher than in the primary tumor, and in metastases with a diameter less than 3 mm, drug levels were two to ten times those in larger ones. Plotting the HMM concentrations versus time, utilizing the data from different patients, the elimination half-lives were found to be 9.05, 8.82, and 8.53 in plasma, tumor, and subcutaneous tissue, respectively.

Adipose Tissue↗
PubMed1982

Species differences in the kinetics and metabolism of fenfluramine isomers.

After single oral doses of racemic fenfluramine to man and animals (male CD-COBS Sprague-Dawley rat, male CD1-COBS mice and male beagle dogs) plasma and/or brain concentrations of the d- and l-isomers and their deethylated metabolite were measured by gas-liquid chromatography. In rat and mouse d-fenfluramine had a longer half-life (T 1/2) and gave a larger area under the curve (AUC) than the l-isomer. These differences were consistent with stereoselective N-deethylation of l-fenfluramine. Thus, in both species the plasma and brain AUC of the l-metabolite were double that of the d-form. In man and dog slight or no differences were seen between te kinetic and metabolic profiles of the isomers. Comparison of the plasma concentrations time curve of fenfluramine showed slower elimination in man than in the other species. The T 1/2 of the d-isomer was 2.6 hr in rat, 2.5 +/- 0.2 hr in the dog. 4.3 hr in the mouse and 17.8 +/- 0.9 hr in man. The deethylated metabolite norfenfluramine was present in plasma or brain, or both, of all the species examined as a major metabolite of the drug. At the oral doses of racemic fenfluramine tested the ration of the AUC for d-norfenfluramine to d-fenfluramine was 4.4, 2.0, 0.8, 0.3, and the dog, rat man and mouse respectively. The T 1/2 of the metabolite was longer than that of the parent drug in all these species. Similar studies with d-fenfluramine indicated that its kinetic profile was identical to that of d-fenfluramine administered in the racemic form. The l-isomer therefore does not change the absorption, distribution and metabolism of the d-isomer which should be considered as the active form.

Adult↗
PubMed1981

Differential adriamycin distribution to blood components.

The differential distribution of doxorubicin (Adriamycin = AM) and daunorubicin (Daunomycin = DM) within the blood components, after an i.v. injection of 10 or 15 mg/kg of body weight, was investigated from its metabolites and quantified by means of the TLC scanning fluorescence technique. AM accumulated in the following order (of decreasing percentages): plasma and red cells (RBC), white cells (WBC), and platelets (PT), but the absolute amount of drug that reached each cell type was related to its relative volume. In the presence of higher blood concentrations (after injection of 15 mg/kg of body weight) the RBCs accumulated much more AM than the plasma, WBC, and PT; suggesting that the RBC fraction has a greater capacity to concentrate the drug. However, if the concentration of AM is expressed per unit volume of each component, a markedly higher value was observed for PT, and this was confirmed by in vitro results obtained by incubating blood in the presence of AM. DM seemed to be distributed on a percent basis to a greater extent than AM in the RBC fraction. Both compounds were taken up by blood cells, particularly platelets, to levels in excess of the extracellular concentration.

Animals↗
PubMed1981

Kinetics of fenfluramine isomers in the rat.

The kinetics of fenfluramine isomers were studied in the rat following oral doses of racemic fenfluramine. The data, analyzed using an analogue computer, indicate that the d-fenfluramine is metabolised and excreted at a slower rate than the 1-isomer, resulting in higher plasma and brain concentrations. The kinetic parameters of both isomers were dose-dependent. The rates of disappearance decreased as the dose was raised. The increase in brain area under the curves (AUC) was much greater than the increase of the dose. These findings suggested the rat has a limited capacity for disposition of fenfluramine.

Animals↗