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Biomedical subjects

S Caccia

Publications and source records attributed to S Caccia.

At least 145 records · Page 8Linked to original sources
PubMed1980

Further studies on the mechanism of serotonin-dependent anorexia in rats.

4-(3-Indolyl-2-ethyl) piperidine (LM 5008), 2-(1-piperazinyl) quinoline (quipazine), and metachlorophenylpiperazine (mCPP) were studied for their ability to affect serotonergic mechanisms in vitro. Their relative potency in inhibiting serotonin (5-HT) uptake in vivo and reducing food intake in rats was also examined. mCPP was very potent in displacing 3H-5-HT bound to brain membranes (IC50, 6.2 X 10(-7) M), followed by quipazine, which showed an IC50 of 3.8 X 10(-6) M. LM 5008 was the least effective with an IC50 of 3.6 X 10(-5) M. mCPP and quipazine were less potent than d-fenfluramine in releasing 14C-5-HT from brain synaptosomes, while LM 5008 caused no significant effects at a concentration of 10(-5) M. Conversely, both in vitro and in vivo studies on 5-HT uptake showed that LM 5008 was the most potent compound in inhibiting 5-HT uptake and mCPP the least potent. Since a 50% reduction of food intake was not reached even with a dose of LM 5008 27-times higher than the ED50 for inhibiting 5-HT uptake in vivo, it is suggested that even marked inhibition of 5-HT uptake at central synapses is not sufficient per se to trigger serotonin-dependent anorexia in the rat. Increased release and/or direct stimulation of post-synaptic receptors may be necessary to obtain this effect. This could be of interest for developing new agents which can cause anorexia by interacting with brain serotonin.

Animals↗
PubMed1980

Effects of chronic treatment with di-(2-ethylhexyl) phthalate on rat liver microsomal activities.

The effects of chronic di-(2-ethylhexyl)phthalate (DEHP) on liver microsomal activity were studied in rats. Daily doses of 50 and 500 mg/kg for 4 weeks did not affect O-demethylation, aromatic hydroxylation, N-demethylation, C3-hydroxylation, styrene monooxygenase, glutamic-oxalacetic and glutamic-pyruvic transaminases (GOT, GPT). Inhibition of glutathione-S-transferase A and C and induction of epoxide hydrase, glutathione-S-transferase B and nitroreductase activity were instead observed. Protein, cytochrome P-450 and reduced glutathione levels in liver did not appear to be affected by DEHP pretreatment.

Animals↗
PubMed1980

Species differences in clobazam metabolism and antileptazol effect.

The antileptazol effect of clobazam lasts longer in the mouse than in the rat. After intraperitoneal injection of clobazam (10 mg kg-1) plasma and brain concentrations of the drug and its rate of disappearance were similar in both species, whereas the metabolite N-demethylclobazam was present at higher concentrations and for longer in the mouse than in the rat. Although the exact contribution of the N-desmethylclobazam to the anticonvulsant effect of clobazam cannot be assessed, the longer duration in mice than in rats seems to be associated with different brain accumulations of the metabolite.

Animals↗
PubMed1980

Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels.

Brain distribution and various pharmacological effects of clobazam and diazepam were studied in rats. When given at 10 mg/kg i.p. the compounds reached peak brain levels 15 min after injection, and showed similar half lives. At peak time brain levels were proportional to the dose administered. Very little of the N-desmethylmetabolite of each compound was found in the brain. Clobazam was less effective than diazepam in protecting rats from pentetrazol convulsions. Disrupting rota-rod performance and increasing punished responses in a "conflict" test, the relative potencies ranging from 4 to 8 in the various tests. The results are discussed in relation to the importance of animal species selection for predicting favourable therapeutic effects in humans.

Animals↗
PubMed1979

Pharmacokinetics of fenfluramine enantiomers in man.

The pharmacokinetics of fenfluramine enantiomers were studied in normal volunteers following the administration of single of multiple doses of racemic fenfluramine hydrochloride. Plasma concentrations and half-lives were similar for both enantiomers after single 40 mg of 60 mg doses. However following chronic administration (2 x 40 mg for 10 days), significant differences were observed between the kinetic parameters of the two enantiomers, the l-form of fenfluramine and norfenfluramine accumulating in plasms more than the d-forms.

Adult↗
PubMed1978

Distribution and localization of p-hydroxy-d-amphetamine in rat brain.

p-Hydroxy-d-amphetamine (p-OHdA) penetrates the blood--brain barrier poorly, when given acutely or by repeated systemic treatments, or when formed by biotransformation from administered d-amphetamine. However its distribution is relatively selective as it accumulates in the striatum more than in the brainstem. The rate of disappearance also differs in the two areas, being slower in the striatum than in the brainstem. These findings suggest that p-OHdA might be stored in different compartments. To check whether p-OHdA specificially accumulated in nerve terminals, catecholaminergic nerve endings were destroyed with 6-hydroxydopamine (6-OHDA). It has been shown that p-HOdA accumulates much less in the striatum of 6-OHDA-treated rats than of controls. This effect was not present in the brainstem. Accumulation of p-OHdA was similar after repeated d-amphetamine administration. The results are interpreted as showing that p-OHdA tends to accumulate in dopaminergic structures.

Amphetamines↗
PubMed1978

Stereoselective disposition of fenfluramine enantiomers in the rat.

1. Rats were treated with d-, l-or dl-fenfluramine. The two optical isomers and their metabolites were determined in plasma, red blood cells and brain areas such as striatum and brainstem. 2. In all cases, the levels of d-fenfluramine were higher than those of the l-enantiomer, while levels of the metabolite norfenfluramine were lower for the d- than the l-form. 3. When metabolism of fenfluramine was inhibited by pre-treatment with SKF 525-A, the concentrations of the enantiomers no longer differed.

Animals↗
PubMed1978

Differences in the availability of d- and l-enantiomers after administration of racemic amphetamine to rats.

1. Rats were treated with racemic amphetamine or separately with the single enantiomers. The two optical isomers were determined in several brain areas, in plasma and urine. 2. The concentration of d-enantiomer significantly exceeds that of the l-enantiomer in brain and plasma but not in urine, following administration of racemic amphetamine. In contrast, when the two isomers are given separately, their brain concentrations are similar. 3. Such a difference does not appear in the brain of mice treated with racemic amphetamine or in the brain of rats pre-treated with SKF 525-A, an inhibitor of amphetamine hydroxylation. 4. The possibility that the l-isomer can interfere with hydroxylation of d-amphetamine is discussed.

Amphetamine↗
PubMed1977

Possible storage of (+)-amphetamine in catecholaminergic terminals of the striatum and brainstem.

6-Hydroxydopamine, given intraventricularly, did not affect the high concentrations of (+)-amphetamine present in the rat striatum and brainstem 1 h after its administration but considerably reduced the small amounts of (+)-amphetamine remaining after 5 h. In contrast, 5,6-dihydroxytryptamine did not modify the (+)-amphetamine concentrations at the times tested. These findings suggest that (+)-amphetamine might be stored in the catecholaminergic but not in the serotonergic central terminals.

5,6-Dihydroxytryptamine↗