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Biomedical subjects

L Zecca

Publications and source records attributed to L Zecca.

At least 91 records · Page 5Linked to original sources
PubMed1987

Modification of GABA turnover in the striatum and hippocampus of the rat after zopiclone.

The effects of zopiclone, a non-benzodiazepine compound that interacts with benzodiazepine receptors, on GABA turnover rate and GABA content in the rat striatum and hippocampus have been studied. Intraperitoneal administration of zopiclone reduced the GABA turnover rates in both the striatum and hippocampus, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA). The effect of zopiclone on AOAA-induced accumulation of GABA in the hippocampus and striatum was blocked by the intraperitoneal injection of the benzodiazepine receptor antagonist Ro 15-3505. Furthermore, zopiclone slightly but significantly decreased GABA content in the hippocampus, the decrease being blocked by coadministration of the benzodiazepine receptor antagonist Ro 15-1788. Our results confirm that the GABAergic system plays a role in the mechanism of action of zopiclone.

Aminooxyacetic Acid↗
PubMed1987

Zopiclone potentiates the antinociceptive effect of morphine in rats.

The antinociceptive effect of morphine, as determined by the tail-flick test, was dose-dependently increased by the intraperitoneal injection of zopiclone. The benzodiazepine antagonists Ro 15-1788 (flumazepil) and Ro 15-3505, when intraperitoneally injected, significantly antagonized the effect of intraperitoneal injection of zopiclone on morphine antinociception. Intrathecal injection of zopiclone potentiated morphine antinociception, while the intracerebroventricular injection of zopiclone failed to enhance morphine antinociception and the intracerebroventricular injection of flumazepil to antagonize the intraperitoneal-zopiclone-induced increase in morphine antinociception. These results suggest that benzodiazepine sites are specifically involved in the potentiating effect of zopiclone on morphine antinociception. The anatomical locations of the receptors involved seem to be at the spinal level.

Animals↗
PubMed1987

Effects of lincomycin on the immune system.

The effects of lincomycin on the immune system were studied on patients suffering from chronic bronchitis by means of phagocytosis, chemotaxis and natural-killer tests. The tests were performed before and 2, 4, 8, 12 and 24 h after administration of 600 mg lincomycin i.m. in a single dose. The results indicate that lincomycin stimulates phagocytosis, expressed as enhanced superoxide production (O2-), chemotaxis and the activity of natural killer cells, measured on the basis of their ability to perform a lysis on the K562 tumoral target labelled with 51Cr. The stimulating effects on chemotaxis appear already 2 h after the administration of the drug, while the same effect on phagocytosis and natural-killer activity occurs after 4 h. The maximal stimulating activity on all three parameters can be shown at 8 h and disappears at 24 h.

Adult↗
PubMed1987

Development of nonreducible technetium-99m(III) cations as myocardial perfusion imaging agents: initial experience in humans.

A series of 15 nonreducible technetium-99m(III) complexes of formula tr-[99mTcL(Y)2]+ has been prepared by a general synthetic route based on reductive addition of Y to the technetium-99m (99mTc) intermediate [99mTcL(O)]+. In these complexes, selected for potential use as myocardial imaging agents, L represents one of the two tetradentate Schiff base ligands N,N'-ethylenebis(acetylacetone iminato), (en), or N,N'-propylene-1,2-bis(acetylacetone iminato), (pn), while Y represents a monodentate phosphine, phosphite or isonitrile ligand as exemplified by P(CH3)3, P(OCH3)3 and CN-C(CH3)3. Of these 15 complexes, several with octanol/saline partition coefficients in the range 0.04-20 exhibit significant myocardial uptake in rats and dogs. Of these, none exhibit detectable myocardial washout, providing strong support for the hypothesis that myocardial washout occurs only for those 99mTc(III) cations that undergo in vivo reduction to the neutral 99mTc(II) form. Evaluation of the prototypical complex tr-[99mTc(en)(P(CH3)3)2]+ in seven normal volunteers and patients establishes that it is only a mediocre myocardial imaging agent in man.

Animals↗
PubMed1986

Effects of 2-chloroadenosine on hippocampal GABA content and turnover.

The effects of 2-Chloroadenosine (CADO), a stable analog of adenosine, on GABA turnover rate and GABA content in the rat hippocampus in vivo have been studied. The intracerebroventricular injection of CADO reduced the GABA turnover rate in the hippocampus, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase (GABA-T) by aminooxyacetic acid (AOAA). The effect of CADO on AOAA-induced accumulation of GABA in the hippocampus was blocked by the intraperitoneal injection of the adenosine receptor antagonist caffeine. Furthermore, CADO at the dose of 5 micrograms per ventricle produced a significant decrease in GABA content in the hippocampus. Our results support the hypothesis that adenosine exerts inhibitory effects on GABAergic circuits in the hippocampus.

2-Chloroadenosine↗
PubMed1986

Age-related multiple-dose pharmacokinetics and anxiolytic effects of delorazepam (chlordesmethyldiazepam).

The kinetics of delorazepam (chlordesmethyldiazepam; CDDZ), and its major metabolite, lorazepam (LRZ) during multiple-dose therapy have been evaluated in two groups of patients with primary or secondary anxiety. The 12 patients in group 1 were 46.8 +/- less than 13.2 years while the eight in group 2 were significantly older (69.7 +/- 7.8 years). All patients were given 0.5 mg twice daily of CDDZ for 30 days. Concentrations of CDDZ and LRZ in multiple blood samples collected during the study were determined by electron-capture gas-liquid chromatography. The degree of anxiety was evaluated from the Hamilton rating scale for anxiety (HRSA). CDDZ and LRZ accumulated in plasma but the rate of accumulation of CDDZ was slower than expected from studies in young volunteers and the half-life values were significantly related to age. Steady-state levels of glucuronated LRZ were also lower in elderly patients. Data indicate that CDDZ is more slowly eliminated and less metabolized as age increases. While pre-treatment scores of HRSA were similar in the two groups, older patients improved significantly less than those of group 1 and had also an higher incidence of side-effects. CDDZ levels positively correlated with improvement in group 1 but not in group 2.

Adult↗
PubMed1986

No-carrier-added fluorine-18-labeled N-methylspiroperidol: synthesis and biodistribution in mice.

No-carrier-added fluorine-18- (18F) labeled N-methylspiroperidol (4) was synthesized from four different substrates: p-nitrobenzonitrile (1), cyclopropyl p-nitrophenyl ketone (2A), p-cyclopropanoyl-N,N,N-trimethylanilinium iodide (2B) and p-cyclopropanoyl-N,N,N-trimethylanilinium perchlorate (2C) using the nucleophilic aromatic substitution reaction. Radiochemical yield, synthesis time, experimental simplicity, and specific activity were compared. In addition, factors which influence the yield of the nucleophilic aromatic substitution were studied. Based on these studies, the synthesis of 4 from 2A maximizes product specific activity and experimental simplicity and provides 4 in 10-15% radiochemical yield [based on [18F-] with a mass of less than 2 nmol and a specific activity of greater than 10 Ci/mumol (EOB)]. The synthesis of 4 from 8-[4-(4-nitrophenyl)-4-oxobutyl]-3-methyl-1-phenyl-1,3,8-triazaspiro+ ++ [4.5]decan-4-one (5) and Cs[18F] using the nucleophilic aromatic substitution reaction gave unacceptably low and erratic yields. The biodistribution of 4 in mice showed a maximum brain uptake of 1.1% of the administered dose at 5 min and declined to approximately 0.6% at 120 min.

Animals↗
PubMed1986

Evaluation in dogs and humans of three potential technetium-99m myocardial perfusion agents.

The biodistribution of the three cationic 99mTc complexes [99mTc(TMP)6]+, [99mTc(POM-POM)3]+, and [99mTc(TBIN)6]+--where TMP represents trimethylphosphite, POM-POM represents 1,2-bis(dimethyoxyphosphino)ethane, and TBIN represents t-butylisonitrile--have been evaluated in humans and dogs. Each agent was studied in three normal volunteers at rest, while [99mTc(POM-POM)3]+ and [99mTc(TBIN)6]+ were each studied in one normal volunteer at exercise. Even though all three agents yield good myocardial images in dogs, none appear suitable for clinical use as myocardial perfusion imaging radiopharmaceuticals. In humans, [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ clear very slowly from the blood and provide myocardial images only several hours after injection. [99mTc(TBIN)6]+ clears rapidly from the blood, but accumulation in the lung obscures the myocardial image for the first hour after injection; at later times, activity in the liver and spleen masks the apical wall. These results correlate with the blood-binding properties of the three complexes. [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ bind tightly to the plasma of human blood, but not to the plasma of dog blood; [99mTc(TBIN)6]+ does not bind tightly to the plasma of either dog or human blood. Among the Tc(I) complexes studied to date in humans, [99mTc(TBIN)6]+ appears to be unique in biodistribution pattern, blood-binding properties, and the fact that exercise improves the ultimate myocardial image. All the Tc(I) complexes appear to undergo myocardial accumulation by a mechanism different from that utilized by Tc(III) complexes. Animal studies alone are not adequate to evaluate the potential utility of 99mTc cationic complexes for myocardial perfusion studies.

Animals↗
PubMed1985

Relative bioavailability in humans for oral tablets and solutions of lormetazepam.

A study was carried out to estimate the relative bioavailability of 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1-methyl-1, 3-dihydro-1H-1,4-benzodiazepine-2-one (lormetazepam, Minias) in humans after administration of oral tablets and solutions. Plasma concentration of the drug was measured by gaschromatography with electron capture detector. Six healthy males were each given both formulations. With the oral solution higher plasma peak concentration and a shorter peak time were observed than with tablets. Also the elimination half-life was shorter with the oral solution, while no difference was found with the AUC.

Administration, Oral↗
PubMed1984

Purine involvement in morphine antinociception.

The effects of a series of adenosine derivatives on morphine antinoceptive effect were investigated in rats by the 'tail-flick' method. 2-Chloroadenosine (CADO) and L-N6-phenylisopropyladenosine (L-PIA), given intraperitoneally, caused decreased morphine antinociception. Intracerebroventricular injections of CADO, L-PIA and 5'-N-ethylcarboxamide adenosine (NECA), but not of 2'-deoxyadenosine, antagonized morphine antinociception. The effects of both central and peripheral injections of CADO and L-PIA on morphine antinociception were partially reversed by caffeine. Intracerebroventricular injection of dibutyryl-cyclic 3', 5' adenosine monophosphate (db cyclic AMP) had no effect on morphine antinociception. These data indicate that adenosine plays a role in morphine-induced antinociception. The results are discussed in terms of postulated effects of adenosine derivatives on adenylate cyclase.

2-Chloroadenosine↗
PubMed1983

Failure of inhibition by TRH of L-Dopa stimulated GH secretion in patients with alcoholic cirrhosis of the liver.

We have investigated the effects of a single oral dose of L-Dopa (500 mg) or of an i.v. infusion of TRH (1 mg dissolved in 400 ml of saline solution) or both administered together, on GH release in men with alcoholic cirrhosis of the liver, and compared them with responses in normal subjects. The results obtained in normal subjects confirm that TRH does not modify plasma GH levels, L-Dopa elevates GH concentrations, while the administration of these two drugs together significantly inhibits GH release induced by oral L-Dopa. In contrast, in patients with alcoholic cirrhosis of the liver, the following results were obtained: 1 TRH infusion significantly increased plasma GH levels which were steadily elevated throughout the experiment; 2 oral administration of L-Dopa provoked a significant rise in blood GH over the basal values similar to that observed in normal subjects; 3 when TRH and L-Dopa are administered at the same time a GH increase like that observed after L-Dopa alone was obtained. These results clearly demonstrate that in patients with alcoholic cirrhosis of the liver the normal inhibitory effect of TRH on L-Dopa induced GH release is completely lost.

Adult↗