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• W2079552625 endingPage "36" @default.
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• W2079552625 abstract "1 RP 62203 (2-[3-(4-(4-fluorophenyl)-piperazinyl)propyl]naphto[1,8-cd]isothiazole-1,1-dioxide) is a novel naphtosultam derivative which shows very high affinity for 5-HT2 receptors in the rat cerebral cortex (Ki = 50.0 pm). 2 RP 62203 is relatively selective for this sub-type of 5-hydroxytryptamine (5-HT) receptor, having lower affinity for the 5-HT1A receptor and very low affinity for the 5-HT3 receptor. RP 62203 displayed low to moderate affinity for α1-adrenoceptors, dopamine D2 receptors and histamine H1 receptors. 3 In vivo binding experiments demonstrated that oral administration of low doses of RP 62203 led to a long-lasting (> 6 h) occupation of cortical 5-HT2 receptors (ID50 = 0.39 mg kg−1). 4 In cortical slices from the neonatal rat, RP 62203 potently inhibited inositol phosphate formation evoked by 5-HT, with an IC50 of 7.76 nm. 5 The activity of neurones in the raphé and their responses to microiontophoretically applied 5-HT were studied with extracellular recording electrodes in the anaesthetized rat. RP 62203 potently and dose-dependently blocked excitations evoked by 5-HT when administered at doses of 0.5–4.0 mg kg−1, i.p. In contrast, neither 5-HT-evoked depressions nor glutamate-evoked excitations of raphé neuronal firing were blocked by RP 62203 at doses as high as 8.0 mg kg−1 i.p. 6 Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) could be abolished by low doses of RP 62203 in mice (ED50 = 0.44 mg kg−1, p.o.) and in rats (ED50 = 1.54 p.o.). Similar results were obtained with mescaline and 5-hydroxytryptophan (5-HTP). 7 The potency of RP 62203 was compared with that of three other 5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ICI 170,809. In all models, RP 62203 showed similar activity to ritanserin, whilst either ICI 169,369 or ICI 170,809 was several fold less active. 8 It is concluded that RP 62203 is a potent and selective antagonist at 5-HT2 receptors in the rodent central nervous system." @default.
• W2079552625 created "2016-06-24" @default.
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• W2079552625 date "1992-01-01" @default.
• W2079552625 modified "2023-10-18" @default.
• W2079552625 title "Pharmacological characterization of RP 62203, a novel 5-hydroxytryptamine 5-HT2 receptor antagonist" @default.
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• W2079552625 doi "https://doi.org/10.1111/j.1476-5381.1992.tb14206.x" @default.
• W2079552625 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1908636" @default.
• W2079552625 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1596688" @default.
• W2079552625 hasPublicationYear "1992" @default.
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