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Biomedical subjects

A Lucacchini

Publications and source records attributed to A Lucacchini.

At least 163 records · Page 9Linked to original sources
PubMed1987

A 3H-flunitrazepam binding inhibitor is present in psychiatric patients' sera.

We investigated the possible existence of endogenous compounds acting on benzodiazepine central receptors in the serum of patients with panic attacks or depression. Our results show the presence of a substance which inhibits the 3H-flunitrazepam binding specifically in the samples taken from the patients' groups, and which is not present in normal controls, in the range of concentrations used. This compound has a molecular weight below 1,000 daltons, is heat-stable, and resistant to proteolytic degradation. The demonstration of this inhibitor opens new perspectives in the study of the biochemistry of anxiety.

Adolescent↗
PubMed1987

Evidence for the existence of a specific binding site for indomethacin on bovine vesicular gland microsomes.

Using bovine vesicular gland microsomes and [14C]indomethacin we demonstrated the presence of a specific binding site for nonsteroidal anti-inflammatory drugs. Specific binding of [14C]indomethacin to microsomes was rapid, with most of the ligand bound by 2 min at 4 degrees C. In routine binding assays the incubation temperature was maintained at 4 degrees C, because the maximal specific binding was obtained. Specific [14C]indomethacin binding appeared to increase linearly with increasing protein concentration over the range of 0.1-1.0 mg of microsomal protein. Specific binding was saturable and Scatchard analysis of binding data showed a single class of binding sites with a dissociation constant (Kd) of 3.8 microM and a maximal number of binding sites (Bmax) of about 1272 pmol/mg of protein. When these binding data were plotted according to the Hill equation, a straight line was obtained with a Hill coefficient of 1.0. Structural specificity of the nonsteroidal anti-inflammatory drug site was studied with diclofenac, arylpropionic acids (ketoprofen and indoprofen), and aspirin. Diclofenac and arylpropionic derivatives were able to compete with [14C]indomethacin for binding to microsomes, while aspirin was a weak inhibitor.

Animals↗
PubMed1986

4-Benzoyl- and 4-benzyl-1,2,3-triazol-N-acetic acids, in vitro inhibitors of the prostaglandin synthesis.

Several 4-benzoyl- and 4-benzyl-1,2,3-triazol-N-acetic derivatives were synthesized and tested. The compounds were prepared by nucleophilic substitution, 1,3-dipolar cycloaddition and usual functional group conversion reactions. Numerous derivatives were evaluated in vitro for their ability to inhibit the prostaglandin synthesis and to displace labelled [14C]indomethacin from bovine vesicular gland microsomes. Some compounds showed biological activity.

Animals↗
PubMed1986

Pyrazolo[4,5-c]quinolines. 3. Synthesis, receptor binding, and 13C NMR study.

Some 1-aryl-3-methylpyrazolo[4,5-c]quinolin-4-ones, were prepared and tested for their ability to displace specific [3H]flunitrazepam binding from bovine brain membranes. The 1-meta-aryl derivatives were the compounds that bound with the highest affinity within this class. Our 13C NMR study suggested a correlation between the binding affinity and the chemical shift value of a carbon atom of the tricyclic system.

Animals↗
PubMed1986

Pyrazolo[4,5-c]quinolines. 2. Synthesis and specific inhibition of benzodiazepine receptor binding.

A series of 1-aryl-3,5-dimethyl-4,5-dihydro-1H-pyrazolo[4,5-c]quinolin-4-ones (2a-e) and 1-aryl-3-methyl-1H-pyrazolo[4,5-c]quinolines (3-7a-e) bearing different substituents at position 4 were prepared and tested for their ability to displace specific [3H]flunitrazepam binding from bovine brain membranes. The 5-N-methyl derivatives 2a-c,e were the compounds that bound with the highest affinity within this class. The replacement of the carbonyl group with other substituents and the resulting aromatization of the pyridine moiety greatly decreased the binding affinity. From a Lineweaver-Burk analysis on the most active compound 2b, it appears that the inhibition is a competitive one.

Animals↗
PubMed1986

Synthesis of new 6H-indolo[2,3-b] [1,8]naphthyridines and their specific inhibition of benzodiazepine receptor.

Some 3-amino- and 3-hydroxy-8-halosubstituted 6H-indolo[2,3-b] [1,8]naphthyridines were synthesized and tested for their affinity for the benzodiazepine receptor in bovine cortical membranes. All prepared compounds were more active than the corresponding 8-unsubstituted derivatives. Moreover, among these compounds the 8-chloroindolonaphthyridines were clearly the most potent.

Animals↗
PubMed1986

N-benzyl-4-phenyl-1,2,3-triazole derivatives as in vitro inhibitors of the prostaglandin synthesis.

Numerous N-benzyl-4-phenyl-1,2,3-triazole derivatives were synthesized and tested. The compounds were prepared by nucleophilic substitution, 1,3-dipolar cycloaddition and usual functional group conversion reactions. Several derivatives were evaluated in vitro for their ability to inhibit prostaglandin synthesis and to displace labelled [14C] indomethacin from bovine vesicular gland microsomes. Some compounds showed biological activity.

Animals↗
PubMed1985

4-(4-Phenylsubstituted)-1,2,3-triazolacetic acid derivatives in vitro inhibitors of prostaglandin synthesis.

New 4-(4-phenylsubstituted)-1,2,3-triazolacetic acid derivatives of general formula (I) were prepared by nucleophilic substitution, 1,3-dipolar cycloaddition and functional group interconversion reactions. These compounds were evaluated as in vitro prostaglandin synthesis inhibitors. Only the isomeric compounds (II c) and (III e), with a 4-aminophenyl substituent on the triazole ring, inhibit arachidonic acid-induced malondialdehyde formation in human platelets; (II c) and (III e) are as effective as aspirin.

Anti-Inflammatory Agents↗
PubMed1985

Specific inhibition of benzodiazepine receptor binding by some N-(indol-3-ylglyoxylyl)amino acid derivatives.

Several N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for their affinity for the benzodiazepine receptor in bovine cortical membranes. From these compounds, the N-[(5-chloro-, 5-bromo-, or 5-nitroindol-3-yl)glyoxylyl]glycine or -alanine esters were clearly the most potent, while the 5-methoxy analogues were considerably less active. Moreover, esters were more active than the corresponding acids. It is concluded that the affinity of these derivatives for the benzodiazepine receptor is profoundly dependent on amino acid molecular size, as well as the hydrophobic and electronic properties of the compounds.

Alanine↗
PubMed1985

Effects of unilateral lesion of the inferior olive on L-[3H] aspartate receptors binding in synaptic membranes of cat cerebellar cortex.

In adult cats, local injection of kainic acid (KA) in the inferior olive (IO) of one side, from which the crossed olivocerebellar projection originates, produced asymmetric postural and motor deficits, attributed to selective damage of the olivary neurons. Since aspartate is one of the putative transmitters of the olivocerebellar fibers, experiments were performed to find out whether 6-8 days after injection of KA within the IO of one side produced changes in aspartate receptors binding in different zones of the cerebellar cortex. In particular, binding in the contralateral zones of the cerebellar cortex was referred to proteins contained in membrane suspensions and compared with the control values obtained in the same experiments from the ipsilateral zones. Binding of L-[3H] aspartate decreased on the average to 53.4% of the control value in the medial zone and to 86.1% of the control value in the intermediate and lateral zones of the cerebellar cortex. This reduction varied in different experiments according to the side of the injection, in agreement with the well known pattern of regional distribution of the olivocerebellar projection within the cerebellar cortex. These findings favour aspartate as the putative neurotransmitter of the climbing fibers. The demonstration that binding of aspartate decreased in the cerebellar cortex of one side, 6-8 days after injection of KA in the corresponding IO, indicates that plastic events occur at this level following destruction of the olivocerebellar pathway. In particular, the reduced binding can be attributed either to a decrease in number of the postsynaptic receptor sites for aspartate or to a decreased affinity of this amino acid for the corresponding receptors. These findings, however, do not exclude that an hypersensitivity by denervation may occur at the level of individual Purkinje cells when they are deprived of the climbing fibers input. In order to answer this question further experiments are required to find out how the binding for aspartate is modified at increasing time intervals after the olivary lesion.

Animals↗
PubMed1983

Solubilization of rat kidney benzodiazepine binding sites.

The high-affinity binding site for [3H]Ro 5-4864 has been solubilized from rat kidney using 1% Triton X-100. After lowering the concentration of detergent and using a poly(ethylene glycol) gamma-globulin assay, it has been possible to demonstrate solubilization of about 90% of the binding sites. A single soluble class of binding sites with a Kd of 1.8 nM is found. The order of potency of benzodiazepines is identical for the solubilized receptor and the membrane-bound form. Gel filtration revealed a major peak of binding activity with apparent molecular weight of 215000 and a Stokes' radius of 5.03 nm.

Amphetamines↗
PubMed1983

[3H]muscimol binding site on purified benzodiazepine receptor.

The presence of a [3H]muscimol binding site on the purified benzodiazepine receptor was demonstrated. The purified protein was apparently homogeneous as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (stained with silver), with a molecular weight of 60,000 +/- 3000. The benzodiazepine binding sites were characterized as being of the central type and the [3H]flunitrazepam binding was enhanced by GABA. This activation was antagonized by bicuculline. [3H]Muscimol specifically binds to the benzodiazepine receptor. The Scatchard plot indicates a Kd of 23 nM and the ratio [3H]flunitrazepam/[3H]muscimol is approximately unity.

Animals↗
PubMed1983

1,2,3-Triazole derivatives of salicylic acid.

This paper describes the preparation of 1,2,3-triazole derivatives of salicylic acid from the methyl 4-azidosalicylate, by 1,3-dipolar cycloaddition reactions to beta-ketoesters, beta-ketoamides, beta-diketones and to symmetrical or asymmetrical alkynes. Other derivatives were obtained by hydrolysis and decarboxylation reactions. Some compounds were evaluated for antiinflammatory activity by an in vitro test based upon the inhibition of the cyclooxygenase enzyme, but they generally showed a weak activity.

Blood Platelets↗
PubMed1982

Inactivation of benzodiazepine binding sites by N-ethylmaleimide.

The benzodiazepine receptors of bovine brain membranes have been identified by the specific binding of radiolabeled [3H]diazepam. Pretreatment of membranes with N-ethylmaleimide causes a dose- and time-dependent decrease of 45 to 60% in the number of binding sites. No decrease occurs when membranes are pretreated with N-ethylmaleimide before administration, or in the presence, of diazepam. Binding of [3H]diazepam to the remaining sites occurs with the same characteristics as binding to the untreated receptor population.

Animals↗
PubMed1982

Isolation of putative benzodiazepine receptors from rat brain membranes by affinity chromatography.

The benzodiazepine receptor from rat brain was solubilised and purified 5200-fold by affinity chromatography. The affinity column contained an immobilized benzodiazepine (delorazepam) and biospecific elution with 6 mM-chlorazepate was achieved. The purified receptor is apparently homogeneous in SDS-polyacrylamide gel electrophoresis. The native protein had a molecular weight of 240,000, and the subunit one of 60,000. The dissociation constant (KD) is 8 nM for [3H]diazepam. A correlation exists between the value of affinity obtained for benzodiazepine derivatives and their known pharmacological effectiveness.

Animals↗