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Biomedical subjects

T Mennini

Publications and source records attributed to T Mennini.

At least 163 records · Page 9Linked to original sources
PubMed1984

Receptor binding profile of tibalosine, a new antihypertensive.

The ability of 1-(2,3-dihydro-5-benzo[b]thienyl]-2-(4-phenylbutylamino)-1- propanol-(erythro) (tibalosine, CP 804 S), a new antihypertensive agent, to interact with 11 different receptors has been studied by binding assays. Tibalosine interacts specifically with alpha- and beta-adrenergic receptors and calcium channel binding sites. Ki values (nmol/l) for inhibition of specific binding are 26, 1000, 1000 and 770 respectively for the alpha 1-adrenergic, beta 1- and beta 2-adrenergic receptors and calcium channel binding sites. The interaction with adrenergic receptors is stereoselective since CP 804 S/T, the threo derivative of tibalosine, exhibits Ki values 8 to 10 times higher than those of tibalosine. The selectivity ratio between alpha 1- and alpha 2-adrenergic receptors is about 400. Tibalosine and CP 804 S/T interact with the low affinity binding sites labelled by 3H-WB 4101 in rat brain membranes. These binding sites for putative Ca2+ channel inhibitors are present in rat heart membranes and have the same characteristics as those in rat brain membranes. These results are discussed in relation with the mechanism of tibalosine antihypertensive effect.

Animals↗
PubMed1983

Modifications in recognition sites for neurotransmitters in rat hippocampus by kainic acid lesion.

The specific binding of the tritiated radioligands of dexetimide, serotonin, clonidine, prazosin, WB-4101 and dihydroalprenolol to hippocampal membranes was determined two weeks after producing a virtual complete degeneration of perikarya by the local application of 0.5 micrograms of kainic acid in the dorsal and ventral parts of the hippocampus. Afferent terminals were unaffected by the neurotoxin since the contents of noradrenaline, serotonin and acetylcholine, as well as the activity of choline acetyltransferase, were not modified. Scatchard analysis revealed that the kainic acid lesion produced a 60% decrease in the density of both cholinergic muscarinic binding sites and serotonin binding sites. A significant portion of alpha 1- and alpha 2-adrenoceptor binding sites are also associated with intrinsic neurons of the hippocampus, as shown by the approximately 30% reduction in the densities of tritiated WB-4101, prazosin and clonidine produced by the action of kainic acid. By contrast, the affinity and density of beta-adrenoceptor binding sites were unaffected by the lesion. It is suggested that the recognition sites of the different receptor populations surviving the lesion most likely reside on homologous and/or heterologous nerve terminals.

Animals↗
PubMed1983

Differences between d-fenfluramine and d-norfenfluramine in serotonin presynaptic mechanisms.

The abilities of d-fenfluramine (d-F) and that of d-norfenfluramine (d-NF) to inhibit [3H]serotonin ([3H]5-HT) accumulation in normal and reserpinized synaptosomes were compared to establish to what extent the serotonin-releasing activity of the two drugs might contribute to reduced accumulation of [3H]5-HT. The results indicate that the inhibitory action of (d-NF) on [3H]5-HT accumulation is due principally to its ability to release [3H]5-HT. In contrast, the interference of release in accumulation studies does not seem to play an important role for d-F, suggesting that release from the granular pool and true uptake inhibition are two different mechanisms by which d-F affects serotonin neurons in vitro.

Animals↗
PubMed1982

Selective changes of receptor binding in brain regions of aged rats.

Binding to several receptors was compared in brain regions of 3 and 21-23 month-old rats. In crude membrane preparations of aged rats the number of dopamine antagonist receptors in striatum was much reduced (-53%). beta-Noradrenergic receptors (cortex) and benzodiazepine receptors (hippocampus and cerebellum) were less but significantly reduced and serotonergic receptors, alpha 1 noradrenergic receptors (both in cortex) and dopamine agonist receptors (striatum) were unchanged. For each receptor binding the KD values were the same in young and old animals. GABA receptor binding (hippocampus and cerebellum) evaluated at only one 3H-GABA concentration (8 nM) was similar in both groups when expressed per protein content but significantly reduced in aged rats when expressed per tissue wet weight because of the partial purification of the synaptic membranes used for 3H-GABA binding. In our experimental conditions age-related changes of specific binding sites in the central nervous system were selective for some receptors studied and did not seem to be due to general non-specific modification of brain tissue composition.

Adrenergic alpha-Antagonists↗
PubMed1982

Selective reduction of one class of dopamine receptor binding sites in the corpus striatum of aged rats.

In aged rats (21-23 vs 3 month) the neuroleptic receptor number was reduced in the striatum (--53%), in the limbic area (--36%), and not changed in the cortex. The in vitro pharmacological profile of the remaining [3H]spiroperidol receptors in each area was not modified in aged animals. The binding of [3H]ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene) in the striatum and of [3H]serotonin ([3H]-5 HT) in the cortex was also the same in both age groups.

Aging↗
PubMed1982

Brain levels of tofizopam in the rat and relationship with benzodiazepine receptors.

The effect of tofizopam on 3H-flunitrazepam binding was studied in rat hippocampus and cerebellum. Tofizopam (at a concentration of 10(-7) M) increased 3H-Flu binding through a 30% rise in the Bmax with no modification of Kd in either brain area. Similar results were obtained when the binding was measured in tofizopam (50 mg/kg p.o.) pretreated rats. Even though tofizopam has no anticonvulsive action against pentetrazol-induced convulsions, it significantly potentiated the action of diazepam but with no modification of brain diazepam levels and metabolism. The brain levels of tofizopam are reported and compared to plasma levels after oral administration of 5 and 50 mg/kg to rats.

Animals↗
PubMed1982

Notes on buspirone's mechanisms of action.

Buspirone is a novel psychotropic drug with clear anxiolytic activity in man. There are a number of neurochemical differences between buspirone and both neuroleptics and benzodiazepines. Moreover, buspirone is extensively metabolized, and several metabolites are present in the brain together with the parent compound. One of these, 1-PP, is present in the brain at higher concentrations than the parent drug, particularly when the drug is given orally. On the basis of the reported experimental data, it can be postulated that buspirone's anticonflict activity in rats may be mediated, at least partially, through 1-PP, without involving any effect on the dopaminergic system. The possibility that buspirone and 1-PP may mimic the action of benzodiazepine on some sites in the complex benzodiazepine-GABA receptors is discussed.

Acetylcholine↗
PubMed1982

d-Amphetamine-induced anorexia and motor behavior after chronic treatment in rats: relationship with changes in the number of catecholamine receptor sites in the brain.

No tolerance to the anorectic activity of d-amphetamine was found in rats given two daily injections of 1.25 mg/kg for 28 days. Such rats also presented no changes in the number of binding sites for serotonin and catecholamines in various brain areas. A 28-day treatment with 10 mg/kg d-amphetamine twice daily caused a significant reduction in the number of binding sites for 3H-dihydroalprenolol (beta adrenergic receptor ligand) in hippocampus, and 3H-spiroperidol (dopamine receptor ligand) in striatum and nucleus accumbens. This treatment did not modify the anorectic effect of 1.25 mg/kg of amphetamine but it markedly reduced the motor hyperactivity induced by this treatment and completely blocked the stereotyped licking and biting induced by apomorphine. Amphetamine stereotypy was not significantly reduced but disappeared faster in chronically treated rats. The possible reasons for the different results (tolerance or sensitization) reported by various authors on changes in amphetamine's effects on motor behaviour during chronic treatment are discussed.

Animals↗
PubMed1980

Hyper- and hyposensitivity of central serotonin receptors:[3H]serotonin binding and functional studies in the rat.

The effect of repeated treatment with D-fenfluramine, a serotonin releaser, or methergoline, a serotonin antagonist, on [3H]5-HT binding was studied in various rat brain areas. In animals with the same pretreatments, the anorectic activity of m-chlorophenylpiperazine, a serotonin agonist, was investigated. A 14-day treatment with D-fenfluramine caused a significant decrease in the number of [3H]5-HT binding sites (Bmax) in the diencephalon. A reduction of binding sites was found in the cortex too when D-fenfluramine was administered for 28 days. Methergoline caused no changes of [3H)5-HT binding in any brain area examined when given for 14 days but 28-day treatment led to a significant increase in the striatum, hippocampus and cortex. D-Fenfluramine and methergoline caused, respectively, a decrease and increase in the effect of m-chlorophenylpiperazine on food intake. The data show that central 5-HT receptor numbers and sensitivity may change after repeated treatments with drugs acting on brain serotonin.

Animals↗