Ilario Mereghetti

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Recently we reported the pharmacological characterization of the 9,10-dihydropyrrolo[1,3]benzothiazepine derivative (S)-(+)-8 as a novel atypical antipsychotic agent. This compound had an optimum pK(i) 5-HT(2A)/D(2) ratio of 1.21 (pK(i) 5-HT(2A) = 8.83; pK(i) D(2) = 7.79). The lower D(2) receptor affinity of (S)-(+)-8 compared to its enantiomer was(More)
A series of new compounds containing a benzimidazole, benzothiazole, or benzoxazole nucleus linked to an arylpiperazine by different thioalkyl chains was prepared. They were tested in radioligand binding experiments to evaluate their affinity for 5-HT 1A and 5-HT 2A serotonergic, alpha 1 adrenergic, D1, and D2 dopaminergic receptors. Many of tested(More)
Using rational drug design to develop atypical antipsychotic drug candidates, we generated novel and metabolically stable pyrrolobenzazepines with an optimized pK(i) 5-HT(2A)/D(2) ratio. 5a, obtained by a new palladium-catalyzed three-step synthesis, was selected for further pharmacological and biochemical investigations and showed atypical antipsychotic(More)
The affinities of the enantiomers of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine, 5) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine, 6) were evaluated in receptor binding assays. Compound (+)-(S)-5, the(More)
The wobbler mouse is a model of selective motor neuron degeneration in the cervical spinal cord. Comparing cervical and lumbar tracts of control and diseased mice at the early stage of pathology by proteomic analysis, we identified 31 proteins by peptide mass fingerprint after tryptic digestion and MALDI-TOF analysis, that were differently represented among(More)
In the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl-methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds were tested in binding assays to evaluate their(More)
The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the endothelin peptide family, which includes ET-2, and ET-3. These peptides display a variety of physiological activities including vasoconstriction and the stimulation of cell proliferation in tissues both within and outside of the cardiovascular system. They exert their actions(More)
Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs(More)
With the aim to develop new potent and selective ligands of 5-HT(3)-type serotonin receptors and to acquire more information on their structure-affinity relationships, new thieno[2,3-d]pyrimidine derivatives 32-39 were synthesized and their binding to 5-HT(3) versus 5-HT(4 )receptors was studied. Some of these new compounds exhibit good affinity for(More)
We have tested by [(35)S]-GTPgammaS binding the intrinsic activity of three full agonists (serotonin, 5-methoxytryptamine and 5-methoxy-2-methyl-N,N-dimethyltryptamine) on rat 5-HT(6) receptors cloned in HEK-293 cells, using the scintillation proximity assay. Serotonin and 5-methoxytryptamine are soluble in water, while the agonist(More)