The Experts below are selected from a list of 8391 Experts worldwide ranked by ideXlab platform
Antonio Lucacchini - One of the best experts on this subject based on the ideXlab platform.
-
peripheral type Benzodiazepine Receptor binding sites in platelets of patients with panic disorder associated to separation anxiety symptoms
Psychopharmacology, 2005Co-Authors: Stefano Pini, Claudia Martini, Antonio Lucacchini, Marianna Abelli, Matteo Muti, Camilla Gesi, Marina Montali, B Chelli, Giovanni B CassanoAbstract:Rationale Although it is still a matter of debate whether panic disorder (PD) and separation anxiety (SA) are associated or causally linked disorders, some investigators have suggested that SA may be a specific subtype of panic-agoraphobic spectrum. Several psychiatric disorders, including PD, are associated with lower levels of peripheral-type Benzodiazepine Receptor (PBR).
-
Benzodiazepine Receptor ligands iii synthesis and biological evaluation of 2 and or 3 substituted pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides
Farmaco, 1999Co-Authors: Gabriella Guerrini, Silvia Selleri, Paola Gratteri, A Costanzo, G Ciciani, Barbara Costa, Claudia Martini, F Bruni, Antonio LucacchiniAbstract:A new series of 2- and/or 3-substituted pyrazolo [5,1-c][benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their Benzodiazepine Receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/Receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed.
-
studies on annulated 1 4 benzothiazines and 1 5 benzothiazepines ix imidazo 2 1 d 1 5 benzothiazepines synthesis and in vitro Benzodiazepine Receptor affinity
European Journal of Medicinal Chemistry, 1995Co-Authors: Valeria Ambrogi, Antonio Lucacchini, Giuliano Grandolini, Luana Perioli, Laura Giusti, Claudia MartiniAbstract:Summary The synthesis of three series of 1- and 2-substituted imidazo[2,1-d][1,5]benzothiazepines is accomplished starting from 1,5-benzothiazepin-4-ones. All the synthesized compounds were evaluated for their affinity for the Benzodiazepine Receptor, testing their ability to displace [3H]Flunitrazepam from bovine brain membrane protein. A few of the tested compounds showed good affinity, in particular compound 9a (Ki = 43.00 nM). The GABA-ratio of the active compounds suggests an antagonist or partial agonist activity. The data obtained allow us to draw some comments on the structure-activity relationships.
Martini C - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis and Benzodiazepine Receptor affinity of derivatives of new tricyclic heteroaromatic system pirido[3',2'-5,6]thiopyrano[4,3-c]pyridazin-3(2H,5H)-one
'Wiley', 2005Co-Authors: Primofioe G, Da Settimo F, Marini A.m, Simorini F, La Motta C, Taliani S, S. Laneri, Trincavelli L, Martini CAbstract:Abstract: Derivatives 7-13 of a new tricyclic heteroaromatic system, pyrido[3',2':5,6]thiopyrano[4,3-c]pyridazin-3(2H,5H)-one, were prepared as potential ligands at the Benzodiazepine Receptor, in view of their structural analogy with potent ligands such as the pyrazoloquinolines of the CGS series II, and especially with the benzothiopyrano[4,3-c]pyridazinones VI. They were obtained starting from the versatile ketones 2,3-dihydrothiopyrano[2,3-b]pyridin-4(4H)-one 1 and the corresponding 7-methyl derivative 2, via condensation with glyoxylic acid, and reaction of the intermediate acid mixtures with hydrazine or substituted phenylhydrazines. When evaluated for their binding affinity at the Benzodiazepine Receptor in bovine cortical membranes, the target compounds 8-13 displayed an affinity in the micromolar/submicromolar order. A hypothesis is presented to rationalize these results
-
Benzodiazepine Receptor ligands - III. Synthesis and biological evaluation of 2-and/or 3-substituted pyrazolo[5,1-c][l,2,4]benzotriazine 5-oxides
'Elsevier BV', 1999Co-Authors: Guerrini G, Costanzo A, Bruni F, Ciciani G, Selleri S, Gratteri P, Costa B, Martini C, Lucacchini AAbstract:A new series of 2- and/or 3-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their Benzodiazepine Receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine-5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/Receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed. (C) 1999 Elsevier Science S.A. All rights reserved
-
Benzodiazepine Receptor (BZR) ligands. 5. New 3-alkyloxycarbonyl-, 3-cyclo-alkyloxycarbonyl-, 3-aryloxy-carbonyl derivatives of pyrazolo [5,1-c][1,2,4]benzotriazine 5-oxides: A study on the 3-ester function modification
1999Co-Authors: Costanzo A, Guerrini G, Bruni F, Ciciani G, Selleri S, Costa B, Martini C, Lucacchini A, Ipponi AAbstract:The synthesis of new 3-alkyloxycarbonyl-, 3-cyclo-alkyloxycarbonyl-, 3-aryloxycarbonyl derivatives of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides and their binding affinities at the central Benzodiazepine Receptor (BZR) are reported. The 3-propynyl ester 10 and the 3-benzyl ester 16, having the best affinity values, were chosen for in, vivo testing
-
Benzodiazepine Receptor ligands-Part II. Synthesis and biological evaluation of pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxide
'Elsevier BV', 1998Co-Authors: Costanzo A, Guerrini G, Bruni F, Ciciani G, Selleri S, Costa B, Martini C, Cappelletti S., Lucacchini AAbstract:A new series of 3-, 8-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxides 3 were synthesized and their Benzodiazepine Receptor (BZR) affinities were evaluated in vitro in comparison with their 5-oxide isomers 2. The 4-oxide compounds 3c,m,n,o showed a better Receptor affinity than their corresponding 5-oxide isomers, with an efficacy trend of antagonist/partial inverse agonist. From a structure-affinity relationship point of view some insight in the role played by N-4 and Id-oxide is gained. (C) Elsevier, Paris
-
Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines .10. Synthesis and inhibition of Benzodiazepine Receptor binding of new 1,4-thiazine and 1,5-thiazepine polycondensed heterocycles with steroidal structure
1996Co-Authors: Grandolini G, Lucacchini A, Perioli L, Giannaccini G, Martini CAbstract:Some naphthol [1,2,-b]-s-triazolo[4,3-d]-1,4-thiazine and 1,5-thiazepine and s-triazolo[4',3'-4,5]-1, ,4-thiazino[3,2-c]quinoline derivatives have been synthesized and tested for their ability to displace [H-3]RO 15-1788 binding from bovine brain membranes. Several compounds showed moderate binding affinity for the Benzodiazepine Receptor
Claudia Martini - One of the best experts on this subject based on the ideXlab platform.
-
peripheral type Benzodiazepine Receptor binding sites in platelets of patients with panic disorder associated to separation anxiety symptoms
Psychopharmacology, 2005Co-Authors: Stefano Pini, Claudia Martini, Antonio Lucacchini, Marianna Abelli, Matteo Muti, Camilla Gesi, Marina Montali, B Chelli, Giovanni B CassanoAbstract:Rationale Although it is still a matter of debate whether panic disorder (PD) and separation anxiety (SA) are associated or causally linked disorders, some investigators have suggested that SA may be a specific subtype of panic-agoraphobic spectrum. Several psychiatric disorders, including PD, are associated with lower levels of peripheral-type Benzodiazepine Receptor (PBR).
-
Benzodiazepine Receptor ligands iii synthesis and biological evaluation of 2 and or 3 substituted pyrazolo 5 1 c 1 2 4 benzotriazine 5 oxides
Farmaco, 1999Co-Authors: Gabriella Guerrini, Silvia Selleri, Paola Gratteri, A Costanzo, G Ciciani, Barbara Costa, Claudia Martini, F Bruni, Antonio LucacchiniAbstract:A new series of 2- and/or 3-substituted pyrazolo [5,1-c][benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their Benzodiazepine Receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/Receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed.
-
studies on annulated 1 4 benzothiazines and 1 5 benzothiazepines ix imidazo 2 1 d 1 5 benzothiazepines synthesis and in vitro Benzodiazepine Receptor affinity
European Journal of Medicinal Chemistry, 1995Co-Authors: Valeria Ambrogi, Antonio Lucacchini, Giuliano Grandolini, Luana Perioli, Laura Giusti, Claudia MartiniAbstract:Summary The synthesis of three series of 1- and 2-substituted imidazo[2,1-d][1,5]benzothiazepines is accomplished starting from 1,5-benzothiazepin-4-ones. All the synthesized compounds were evaluated for their affinity for the Benzodiazepine Receptor, testing their ability to displace [3H]Flunitrazepam from bovine brain membrane protein. A few of the tested compounds showed good affinity, in particular compound 9a (Ki = 43.00 nM). The GABA-ratio of the active compounds suggests an antagonist or partial agonist activity. The data obtained allow us to draw some comments on the structure-activity relationships.
Lucacchini A - One of the best experts on this subject based on the ideXlab platform.
-
Benzodiazepine Receptor ligands - III. Synthesis and biological evaluation of 2-and/or 3-substituted pyrazolo[5,1-c][l,2,4]benzotriazine 5-oxides
'Elsevier BV', 1999Co-Authors: Guerrini G, Costanzo A, Bruni F, Ciciani G, Selleri S, Gratteri P, Costa B, Martini C, Lucacchini AAbstract:A new series of 2- and/or 3-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their Benzodiazepine Receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine-5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/Receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed. (C) 1999 Elsevier Science S.A. All rights reserved
-
Benzodiazepine Receptor (BZR) ligands. 5. New 3-alkyloxycarbonyl-, 3-cyclo-alkyloxycarbonyl-, 3-aryloxy-carbonyl derivatives of pyrazolo [5,1-c][1,2,4]benzotriazine 5-oxides: A study on the 3-ester function modification
1999Co-Authors: Costanzo A, Guerrini G, Bruni F, Ciciani G, Selleri S, Costa B, Martini C, Lucacchini A, Ipponi AAbstract:The synthesis of new 3-alkyloxycarbonyl-, 3-cyclo-alkyloxycarbonyl-, 3-aryloxycarbonyl derivatives of pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides and their binding affinities at the central Benzodiazepine Receptor (BZR) are reported. The 3-propynyl ester 10 and the 3-benzyl ester 16, having the best affinity values, were chosen for in, vivo testing
-
Benzodiazepine Receptor ligands-Part II. Synthesis and biological evaluation of pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxide
'Elsevier BV', 1998Co-Authors: Costanzo A, Guerrini G, Bruni F, Ciciani G, Selleri S, Costa B, Martini C, Cappelletti S., Lucacchini AAbstract:A new series of 3-, 8-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 4-oxides 3 were synthesized and their Benzodiazepine Receptor (BZR) affinities were evaluated in vitro in comparison with their 5-oxide isomers 2. The 4-oxide compounds 3c,m,n,o showed a better Receptor affinity than their corresponding 5-oxide isomers, with an efficacy trend of antagonist/partial inverse agonist. From a structure-affinity relationship point of view some insight in the role played by N-4 and Id-oxide is gained. (C) Elsevier, Paris
-
Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines .10. Synthesis and inhibition of Benzodiazepine Receptor binding of new 1,4-thiazine and 1,5-thiazepine polycondensed heterocycles with steroidal structure
1996Co-Authors: Grandolini G, Lucacchini A, Perioli L, Giannaccini G, Martini CAbstract:Some naphthol [1,2,-b]-s-triazolo[4,3-d]-1,4-thiazine and 1,5-thiazepine and s-triazolo[4',3'-4,5]-1, ,4-thiazino[3,2-c]quinoline derivatives have been synthesized and tested for their ability to displace [H-3]RO 15-1788 binding from bovine brain membranes. Several compounds showed moderate binding affinity for the Benzodiazepine Receptor
-
Synthesis and Benzodiazepine Receptor activity of some 4,5-dihydro-1H-pyrazolo[4,3-c][1,8]naphthyridine derivatives.
1994Co-Authors: Da Settimo A, Martini C, Simorini F, Primofiore G, Da Settimo Passetti F, Barili P L, Senatore G, Lucacchini AAbstract:The preparation of 5-substituted 1-aryl-4,5-dihydro-1H-pyrazolo[4,3- c][1,8] naphthyridines by reaction of 5-substituted 3-hydroxymethylene-2,3-dihydro-1,8-naphthyridin-4(1H)-ones with various phenylhydrazines is described. The Benzodiazepine binding activity of these compounds was evaluated in vitro. Only the 5-methyl substituted derivatives showed affinity for the Benzodiazepine Receptor, with K1 values ranging from 2.9 to 0.195 microM for the para-phenyl substituted compounds. A hypothesis of interaction of these ligands with the Receptor site is reported
Robert J. Walker - One of the best experts on this subject based on the ideXlab platform.
-
dual action of the Benzodiazepine Receptor inverse agonist ru34347 on responses to exogenously applied gaba in the rat cerebellar slice
General Pharmacology-the Vascular System, 1999Co-Authors: Ashley K Pringle, C R Gardner, Robert J. WalkerAbstract:The Benzodiazepine Receptor inverse agonist has been shown to produce agonist-like effects at low concentrations. RU34347 has both inverse agonist (attenuation of GABA-responses) and agonist-like (reduction of spontaneous Purkinje cell firing rate) in the cerebellar slice preparation. The Benzodiazepine antagonist flumazenil prevented the inverse agonist actions, but only partially reduced the agonist-like effects. Further, brief application of RU34347 to slices mimicked the response to GABA, and pharmacological investigation determined that this action was mediated through increased GABA through action at a site proximal to the parallel fiber-basket cell synapse, at an as yet undetermined Receptor.
-
Biphasic actions of the Benzodiazepine Receptor inverse agonist ru34347 in the rat cerebellar slice
Brain Research, 1996Co-Authors: Ashley K Pringle, C R Gardner, Robert J. WalkerAbstract:Abstract We have characterised the biphasic response of the Benzodiazepine Receptor inverse agonist RU34347 in the rat cerebellar slice preparation using extracellular electrophysiological recordings from Purkinje cells. RU34347 (10 fM–10 nM) produced an increase in GABAA-mediated inhibition at between 10 fM and 10 nM, a response normally associated with Benzodiazepine agonists. This response was biphasic, being dose dependent between 10 fM and the peak effect at 10 pM, and inversely related to concentration between 100 pM and 10 nM. Associated with this increase in inhibition was a decrease in firing rate, also showing a biphasic concentration-response relationship. The agonist-like response was composed of two elements, an initial increase occurring after 5 min followed by a slow decline over the next 20 min. This second, declining, phase was more evident at higher concentrations of RU34347. The peak effect seen at 10 pM was fully antagonised by 1 μM flumazenil, a Benzodiazepine Receptor antagonist. This concentration of flumazenil also antagonised the decrease in firing rate induced by 10 pM RU34347. The response to 10 nM RU34347 was further characterised since the largest second phase decline was demonstrated at this concentration. 10 nM flumazenil fully antagonised the second, declining, phase of the response, but not the magnitude of the initial increase. A partial antagonism of the peak effect was seen with 1 μM flumazenil, and a full antagonism at 10 μM flumazenil. This effect was similar to that observed with Ro15-4513 in a previous study. Therefore, we investigated the binding of RU34347 to diazepam-insensitive Benzodiazepine Receptors. [ 3 H]Ro 15-4513 was displaced by Ro15-4513, flumazenil and Ro19-4603, but not by RU34347. Therefore, although the electrophysiological data correlate well with that previously reported for Ro15-4513, RU34347 does not displace Ro15-4513 binding at the diazepam-insensitive Benzodiazepine Receptor. Therefore, either both ligands bind to complimentary sites on the same Receptor complex, or both induce a similar physiological response through an action on different Receptors.