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Biomedical subjects

S Garattini

Publications and source records attributed to S Garattini.

At least 397 records · Page 22Linked to original sources
PubMed1973

Correlation between desipramine levels and (-)-noradrenaline uptake and chronotropic effect in isolated atria of rats.

1. The uptake of unlabelled and [(14)C]-desipramine was studied in rat isolated atria incubated in a medium containing concentrations of desipramine ranging from 200 pg/ml to 2 mug/ml. The uptake was found to be dose- and time-dependent. Equilibrium was not reached after 2-3 h of incubation unless concentrations of desipramine higher than 1 mug/ml were used.2. The washout curves of atria previously loaded with desipramine showed that the drug is slowly released and that this release is not influenced by its initial tissue concentration.3. The binding appeared to be at non-specific sites and not at sites where noradrenaline is stored since atria taken from rats treated with 6-hydroxydopamine accumulated the drug at the same rate as control atria.4. The inhibition of (-)-noradrenaline uptake and the potentiation of the chronotropic response to (-)-noradrenaline is correlated with the concentration of desipramine in atria for tissue levels of the drug ranging from 0.01 to 1 mug/g. Higher tissue levels show less potentiation of the effect of (-)-noradrenaline or even inhibition of the maximal response to (-)-noradrenaline. These concentrations of desipramine (> 7 mug/g) markedly depressed the atrial rate.5. The results show that despite the accumulation of desipramine by unspecific sites, concentrations of desipramine in the tissue are correlated with the pharmacological response. Furthermore a gradual shift from potentiation to inhibition of noradrenaline response can be obtained with the same bath concentrations of desipramine by increasing the time of incubation.

Animals↗
PubMed1973

Interaction of (+)-amphetamine with cerebral dopaminergic neurones in two strains of mice, that show different temperature responses to this drug.

1. (+)-Amphetamine sulphate elicits a dose-dependent hyperthermia in NMRI mice but it does not significantly increase the body temperature of C(3)H mice.2. When low doses of (+)-amphetamine are given, the body temperature of C(3)H mice decreases.3. (+)-Amphetamine decreases the noradrenaline concentration in the brain-stem and increases the homovanillic acid concentration (HVA) in the striatum of NMRI mice, but only slightly reduces the noradrenaline concentration and does not change the HVA concentration in the brains of C(3)H mice.4. The two strains appear to show a difference in the metabolism of dopamine in the striatum. The rates at which dopamine disappears from the tissue after blocking catecholamine synthesis with alpha-methyltyrosine and the rates at which HVA accumulates after blocking the active transport of this metabolite out of the brain with probenecid suggest that the turnover of dopamine is lower in C(3)H mice than in NMRI mice.

Animals↗