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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 361 records · Page 20Linked to original sources
PubMed1976

The effect of steroid contraceptives on the concentrations of brain monoamines in rats and mice.

The effect of three estrogen-progestin combinations on biogenic amines in discrete brain areas of rats and mice has been investigated. With the exception of a significant decrease of brain 5-hydroxyindolacetic acid in the rats treated for 30 days with the combination norethynodrel + mestranol, no significant changes in the levels of serotonin, noradrenaline or dopamine in the rat brain were found following the administration of the compounds under study. On the other hand, in mice moderate but significant changes in the levels of serotonin, dopamine, noradrenaline and 5-hydroxyindolacetic acid were found in various brain areas depending on the estrogen-progestin combination used. The potential importance of these effects for the contraceptive as well as for some central actions of these compounds is discussed.

Amines↗
PubMed1975

Pharmacokinetics of nomifensine in man.

Nomifensine pharmacokinetics were determined in healthy volunteers after the oral administration of 50 mg of the drug. Peak plasma levels of 95-177 ng/ml were attained within 1 to 4 hrs, and the apparent plasma half-lives ranged from 3.3 to 4.9 hrs. Assuming 100% bioavailability the drug has a relatively large apparent volume of distribution. From these findings it appears that the pharmacokinetics profile of nomifensine is considerably different from those of other known antidepressants. Implications for dosages schedules are discussed.

Administration, Oral↗
PubMed1975

Epoxides metabolically produced from some known carcinogens and from some clinically used drugs. I. Differences in mutagenicity.

The epoxide metabolites of two clinically used drugs and an experimental psychotropic agent, carbamazepine 10,11-oxide, cyproheptadine 10,11-oxide and cyclobenzaprine 10,11-oxide, were fully devoid of any mutagenic activity under conditions where K-region-epoxide metabolites of some known carcinogens, such as benzo(a)pyrene, proved to be potent frameshift mutational agents for Salmonella typhimurium TA 1537 and TA 1538. All epoxides tested were non-mutagenic for TA 1535, designed to detect substitution mutations. The 10,11-epoxides of the three drugs, carbamazepine, cyproheptadine and cyclobenzaprine, were not cytotoxic to any of the bacterial tester strains used, precluding that mutagenicity might have been overshadowed by cytotoxicity. When the mutagen, precursor, benzo(a)pyrene, was incubated together with TA 1537 and a mammalian microsomal preparation in the presence of a system generating the co-factor necessary for mono-oxygenase activity, activation to mutagenic species was observed which was dramatically increased in the presence of a potent epoxide hydratase inhibitor, 1,1,1-trichloropropene 2,3-oxide, suggesting epoxide(s) as the (or one of the) mutagenically active species metabolically produced in situ. None of these effects was observed with the three medical drugs. Moreover, the observation that the alkene oxide 4-phenylstyrene 7,8-oxide is mutagenic to the two strains TA 1537 and TA 1538 but the K-region arene oxide derived from 7,12-dimethylbenz(a)anthracene is inactive for the latter strain indicates that epoxidation of an aromatic double bond of a polycyclic hydrocarbon is neither a necessary nor a satisfying condition for frameshift mutagenesis to occur.

Benzopyrenes↗
PubMed1975

Gas chromatographic-mass spectrometric determination of intact C3-hydroxylated benzodiazepine glucoronides in urine.

A method is described for the determination C3-hydroxylated benzodiazepine glucuronides in biological samples. Oxazepam and lorazepam glucuronides are measured as methyl esters and trimethylsilyl derivates by a gas chromatographic procedure. The applicability of the method has been tested on the urine of rats, guinea pigs, rabbits and man, receiving oxazepam orally. Oxazepam glucuronide was not found in rat urine but it was present in the urine of rabbits (5.7% of the administered dose), guinea pigs (9.5%) and man (13.4-26.9%).

Administration, Oral↗
PubMed1975

Effect of amphetamine and fenfluramine on brain noradrenaline and MOPEG-SO4.

I.p. administration of d-amphetamine sulphate and fenfluramine-HCl at various doses induced significant modifications of brain noradrenaline (NA) and MOPEG-SO4 (3-methoxy-4-hydroxyphenylethyleneglycol) in the rat. Both drugs induced a decrease in brain noradrenaline but the two compounes seem to interact with the central noradrenergic system through a different mechanism. The decreased levels of noradrenaline after 1-fenfluramine administration were paralleled by increased MOPEG-SO4 levels. The d-isomer of fenfluramine was less active than the l-isomer. Amphetamine was considerably more effective than l-fenfluramine in reducing NA concentration. However, in spite of the long lasting effect on noradrenaline levels the i.p. administration of amphetamine did not lead to an increased MOPEG-SO4 concentration suggesting a more complex interaction with the noradrenergic system.

Animals↗
PubMed1975

The effect of selective lesioning of brain catecholamine-containing neurons on the activity of various anorectics in thr rat.

An intraventricular injection of 6-hydroxydopamine to rats pretreated with pargyline, a procedure which produces a marked decrease of brain catecholamines without significant changes in the serotonin levels, significantly antagonizes the anorectic effect of amphetamine, phentermine, mazindol and diethylpropion, while the reduction of food intake induced by other drugs such as fenfluramine, p-chloroamphetamine, SE 780 and SKF 1-39728 is not significantly affected. The data suggest an involvement of brain catecholamines in the anorectic effect of amphetamine, phentermine, mazindol and diethylpropion whereas other mechanisms appear to be involved in the activity of the other anorectics studied.

Animals↗
PubMed1975

The effect of nomifensine on the depletion of brain serotonin and catecholamines induced respectively by fenfluramine and 6-hydroxydopamine in rats.

Nomifensine, at a dose of 10 mg/kg i.p., completely antagonized the decrease of brain dopamine induced by an intraventricular injection of 6-hydroxydopamine. The decrease of brain noradrenaline was also significantly antagonized by nomifensine. Desipramine antagonized the effect of 6-hydroxydopamine on noradrenaline but not on dopamine. The decrease of brain serotonin induced by fenfluramine was antagonized by chlorimipramine but not by nomifensine. The findings indicate that nomifensine specifically blocks the uptake mechanism for catecholamines in the brain without significant effects on serotonin.

Animals↗
PubMed1975

Effect of fenfluramine on 5-hydroxytryptamine uptake and release by rat blood platelets.

1. (+)-Flenfluramine reduces the central stores of 5-hydroxytryptamine (5-HT) by a poorly understood mechanism. 2. Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings. 3. (+)-Fenfluramine shows a dual effect: it inhibits the uptake of (14C)-5-HT by platelets and it releases newly absorbed (14C)-5-HT from platelets. 4. The inhibition of (14C)-5-HT uptake induced by (+)-fenfluramine appears very rapidly, is concentration-dependent and seems not to be competitive. (+)-Fenfluramine is ten times less effective than chloroimipramine but tem times more effective than (+)-amphetamine; (+)-fenfluramine is more active than its (-)isomer or its metabolite norfenfluramine ((+)- or (-)-form). 5. The release of (14C)-5-HT from platelets induced by (+)-fenfluramine is concentration-dependent but increases wtih increased incubation time. Both chloroimipramine and (+)-amphetamine are in comparison very poor release inducers; (+)-fenfluramine is more active than its (-)-isomer or its metabolites. 6. The effect on (14C)-5-HT uptake exerted by (+)-fenfluramine and chloroimipramine in vitro could not be observed in vivo. 7. The observed effect on fenfluramine on the uptake and release of 5-HT may explain the lowering action of fenfluramine on the brain 5-HT level, an effect considered of importance for the anoretic effect on this drug.

Animals↗
PubMed1975

Effect of selective lesioning of brain serotonin or catecholamine-containing neurons on the activity of oral steroid contraceptives in rats.

The effect of different dosage combinations of lynoestrenol and mestranol were studied in rats that have been subjected to selective lesioning of brain serotonin or catecholamine-containing neurons. Lesions of the midbrain raphe, which cause a marked decrease of serotonin in the forebrain, were without any effect on the estrus cycle, fertility and activity of the steroids under study. An intraventricular injection of 6-hydroxydopamine, which causes a selective decrease of noradrenaline and dopamine in the forebrain, produced a transient effect only on the estrus cycle but did not significantly change the fertility or the activity of the substances investigated. The data indicate that the integrity of monoaminergic neurons in the brain is not an essential condition for the aspects investigated in the present study.

Animals↗
PubMed1975

Levels of piribedil and its active metabolite (S-584) in the rat striatum.

1. A gas chromatographic-mass fragmentographic method has been developed to determine piribedil and its metabolite S-584, using diazepam as internal standard. The metabolite was derivatized as a trimethylsilyl ether for gas chromatographic analysis. The minimum detectable amount of piribedil and the metabolite was 10 ng/g tissue. 2. Levels of piribedil and its metabolite in the striatum were determined by mass fragmentography.

Animals↗