The Experts below are selected from a list of 8826 Experts worldwide ranked by ideXlab platform
Philip G Strange - One of the best experts on this subject based on the ideXlab platform.
-
Binding affinities of several inverse agonists/antagonists are affected by the presence of sodium ions.
2016Co-Authors: Claire L. Newton, Martyn D. Wood, Philip G StrangeAbstract:Competition analyses of the inhibition of [3H]Spiperone binding to membranes prepared from Sf9 cells expressing dopamine D2 (filled symbols) or dopamine D3 receptors (open symbols), by (A) Spiperone, (B) L,741,626, (C) GR 103691 and (D) clozapine, were performed in the absence of monovalent cations (●/○), in the presence of 100 mM NaCl (■/□) or 100 mM NMDG (▲/Δ). Data are mean ± SEM of at least 3 independent experiments.
-
characterization of recombinant human serotonin 5ht1a receptors expressed in chinese hamster ovary cells 3h Spiperone discriminates between the g protein coupled and uncoupled forms
Biochemical Pharmacology, 1993Co-Authors: Hardy Sundaram, Adrian Newmantancredi, Philip G StrangeAbstract:Abstract 5HT 1A serotonin (5-hydroxytryptamine) receptors have been characterized by ligand binding in a recombinant Chinese Hamster Ovary cell line expressing the human receptor gene. The agonist ligand [ 3 H]2-( N , N -dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene ([ 3 H]8-OH-DPAT) and the antagonist [ 3 H]Spiperone were used. For both radioligands the binding sites labelled have the properties of 5HT 1A receptors and most antagonists show roughly equal affinities for the receptors labelled by either [ 3 H]8-OH-DPAT or [ 3 H]Spiperone. Agonists, however, show higher affinities for the sites labelled by [ 3 H]8-OH-DPAT and the antagonist Spiperone conversely shows a higher affinity for the sites labelled by [ 3 H]Spiperone. Whereas [ 3 H]8-OH-DPAT binding is inhibited by guanosine triphosphate (GTP) the binding of [ 3 H]Spiperone is increased by GTP. A model is proposed for the results whereby [ 3 H]8-OH-DPAT labels a form of the receptor coupled to a G-protein and [ 3 H]Spiperone labels a form of the receptor uncoupled from G-proteins (or possibly coupled to a different G-protein).
William B. Guggino - One of the best experts on this subject based on the ideXlab platform.
-
Spiperone elicited currents in CHO cells transfected with wt-CFTR-GFP.
2013Co-Authors: Lihua Liang, Owen M. Woodward, Zhaohui Chen, Robert Cotter, William B. GugginoAbstract:(A): Representative currents attained before adding Spiperone; (B): after adding Spiperone; (C): in the presence of Spiperone, adding CFTR-172 reduced the currents; (D): The summary data of Spiperone effect in stimulating chloride current in CHO cells. Black trace represents before adding Spiperone. Red trace represents after adding Spiperone and blue trace indicates after adding CFTR-172 (n = 5).
-
Spiperone stimulated chloride current by whole cell voltage clamp recording in IB3-1 cells transfected with wt-CFTR-GFP.
2013Co-Authors: Lihua Liang, Owen M. Woodward, Zhaohui Chen, Robert Cotter, William B. GugginoAbstract:(A): Representative currents elicited by 15 mV steps from -100 mV to 125 mV. (B): Currents after addition of Spiperone; (C): Currents after addition of CFTR172; (D): Currents after addition of 4,4-Diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) (E): A representative instantaneous I-V curve. Black trace represents before adding Spiperone, red trace indicates after adding Spiperone, blue trace indicates after adding CFTR inhibitor CFTR172, and green trace indicates after adding DIDS. (F): The summary data of Spiperone stimulated chloride current in IB3-1 cells transfected with wt-CFTR (n = 6). Black trace indicates before adding Spiperone and red trace indicates after adding Spiperone.
-
Tyrosine phosphorylated proteins detected by anti-phosphotyrosine antibodies in IB3-1 cells.
2013Co-Authors: Lihua Liang, Owen M. Woodward, Zhaohui Chen, Robert Cotter, William B. GugginoAbstract:A: Cells were treated with DMSO and Spiperone for 2, 5 and 10 mins. A band at molecular weight around 120 kd was detected by the anti-phosphotyrosine antibody and was enhanced in the Spiperone treated group at 2 and 5 mins. GAPDH is the loading control. B: Statistical analysis of the protein expression enhancement measured by the densitometry analysis. 2 and 5 min treatment with Spiperone significantly increased the protein phosphorylation (n = 3, *P
S D Varfolomeev - One of the best experts on this subject based on the ideXlab platform.
-
A study of the kinetics of the interaction of Spiperone with binding sites on human mononuclear cells : existence of a heterogeneous population of Spiperone binding sites
Journal of Neuroimmunology, 1992Co-Authors: Sergei Zaitsev, A A Koshkin, I I Izumrudova, S D VarfolomeevAbstract:Abstract The kinetics and equilibrium of the interaction of [ 3 H]Spiperone with binding sites on human mononuclear cells were studied using a competitive displacement of Spiperone by ketanserin, sulpirid, haloperidol, (+)- and (−)-butaclamol. [ 3 H]Spiperone binding sites on human mononuclear cells were shown to be not of the D 2 , but most probably of the 5-HT 2 type. The process of [ 3 H]Spiperone binding to these sites conforms to the model of ligand interaction with two independent binding sites (the high-affinity site K d 1 = 3 nM and the low-affinity site, K d 2 = 20 nM), thus suggesting heterogeneity of Spiperone sites on mononuclear cells. We found that in contrast to high-affinity binding sites, low-affinity sites show an essentially lower stability during storage of mononuclear cells.
-
A study of the kinetics of the interaction of Spiperone with binding sites on human mononuclear cells: existence of a heterogeneous population of Spiperone binding sites.
Journal of Neuroimmunology, 1992Co-Authors: S V Zaitsev, A A Koshkin, I I Izumrudova, S D VarfolomeevAbstract:The kinetics and equilibrium of the interaction of [3H]Spiperone with binding sites on human mononuclear cells were studied using a competitive displacement of Spiperone by ketanserin, sulpiride, haloperidol, (+)- and (-)-butaclamol. [3H]Spiperone binding sites on human mononuclear cells were shown to be not of the D2, but most probably of the 5-HT2 type. The process of [3H]Spiperone binding to these sites conforms to the model of ligand interaction with two independent binding sites (the high-affinity site, Kd1 = 3 nM and the low-affinity site, Kd2 = 20 nM), thus suggesting heterogeneity of Spiperone sites on mononuclear cells. We found that in contrast to high-affinity binding sites, low-affinity sites show an essentially lower stability during storage of mononuclear cells.
Lihua Liang - One of the best experts on this subject based on the ideXlab platform.
-
Spiperone elicited currents in CHO cells transfected with wt-CFTR-GFP.
2013Co-Authors: Lihua Liang, Owen M. Woodward, Zhaohui Chen, Robert Cotter, William B. GugginoAbstract:(A): Representative currents attained before adding Spiperone; (B): after adding Spiperone; (C): in the presence of Spiperone, adding CFTR-172 reduced the currents; (D): The summary data of Spiperone effect in stimulating chloride current in CHO cells. Black trace represents before adding Spiperone. Red trace represents after adding Spiperone and blue trace indicates after adding CFTR-172 (n = 5).
-
Spiperone stimulated chloride current by whole cell voltage clamp recording in IB3-1 cells transfected with wt-CFTR-GFP.
2013Co-Authors: Lihua Liang, Owen M. Woodward, Zhaohui Chen, Robert Cotter, William B. GugginoAbstract:(A): Representative currents elicited by 15 mV steps from -100 mV to 125 mV. (B): Currents after addition of Spiperone; (C): Currents after addition of CFTR172; (D): Currents after addition of 4,4-Diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) (E): A representative instantaneous I-V curve. Black trace represents before adding Spiperone, red trace indicates after adding Spiperone, blue trace indicates after adding CFTR inhibitor CFTR172, and green trace indicates after adding DIDS. (F): The summary data of Spiperone stimulated chloride current in IB3-1 cells transfected with wt-CFTR (n = 6). Black trace indicates before adding Spiperone and red trace indicates after adding Spiperone.
-
Tyrosine phosphorylated proteins detected by anti-phosphotyrosine antibodies in IB3-1 cells.
2013Co-Authors: Lihua Liang, Owen M. Woodward, Zhaohui Chen, Robert Cotter, William B. GugginoAbstract:A: Cells were treated with DMSO and Spiperone for 2, 5 and 10 mins. A band at molecular weight around 120 kd was detected by the anti-phosphotyrosine antibody and was enhanced in the Spiperone treated group at 2 and 5 mins. GAPDH is the loading control. B: Statistical analysis of the protein expression enhancement measured by the densitometry analysis. 2 and 5 min treatment with Spiperone significantly increased the protein phosphorylation (n = 3, *P
Richard A. Glennon - One of the best experts on this subject based on the ideXlab platform.
-
Ketanserin and Spiperone as Templates for Novel Serotonin 5-HT2A Antagonists
Current Topics in Medicinal Chemistry, 2002Co-Authors: Richard A. Glennon, Kamel Metwally, Malgorzata Dukat, Abd M. Ismaiel, Joseph De. Los Angeles, Jeffery Herndon, Milt Teitler, Nantaka KhoranaAbstract:The structures of ketanserin (1) and Spiperone (2) were examined in detail to determine the role of various substituent groups on 5-HT2A receptor affinity and selectivity. It was found that the presence of the quinazoline ring of ketanserin detracts from selectivity and that various ring-opened analogs displayed ketanserin-like affinity and up to 30-fold enhanced selectivity. The triazaspirodecanone portion of Spiperone is a major determinant of its 5-HT2A affinity and selectivity. The conformational rigidity imposed by the ring, as well as the nature of the N1-substituent, are important factors in controlling binding at 5-HT2A, 5-HT2C, 5-HT1A, and dopamine D2 receptors. Replacement of the N1-phenyl ring of Spiperone with a methyl group (KML-010 48) resulted in a compound that binds at 5-HT2A receptors with slightly lower affinity than Spiperone, but that lacked affinity (Ki > 10,000 nM) for 5-HT2C and 5-HT1A receptors and binds with 400-fold reduced affinity at D2 receptors.
-
Spiperone: influence of spiro ring substituents on 5-HT2A serotonin receptor binding.
Journal of Medicinal Chemistry, 1998Co-Authors: Kamel Metwally, Malgorzata Dukat, Milt Teitler, Christina T. Egan, Carol Smith, Ann Dupre, Colleen B. Gauthier, Katharine Herrick-davis, Richard A. GlennonAbstract:Spiperone (1) is a widely used pharmacological tool that acts as a potent dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2A antagonist. Although Spiperone also binds at 5-HT2C receptors, it is one of the very few agents that display some (ca. 1000-fold) binding selectivity for 5-HT2A versus 5-HT2C receptors and, hence, might serve as a useful template for the development of novel 5-HT2A antagonists if the impact of its various substituent groups on binding was known. In the present investigation we focused on the 1,3,8-triazaspiro[4.5]decanone portion of Spiperone and found that replacement of the N1-phenyl group with a methyl group only slightly decreased affinity for cloned rat 5-HT2A receptors. However, N1-methyl derivatives displayed significantly reduced affinity for 5-HT1A, 5-HT2C, and dopamine D2 receptors. Several representative examples were shown to behave as 5-HT2 antagonists. As such, N1-alkyl analogues of Spiperone may afford entry into a novel series of 5-HT2A-selective antagonists.
