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• W2000436131 abstract "The pharmacokinetic-pharmacodynamic relationship of S 15535 (1-(benzodioxan-5-yl) 4-(indan-2-yl)piperazine) and its active 5-hydroxy metabolite S 32784 (1-(benzodioxan-5-yl) 4-(5-hydroxyindan-2-yl)piperazine), and buspirone as a reference, were studied in male Wistar rats using a behavioural model of anxiety by determining the reduction in the number of fear-induced ultrasonic vocalisations. S 15535 and buspirone were administered p.o. and i.v. S 32784, present in man but not in rat, was administered i.v. The pharmacokinetics and pharmacokinetic-pharmacodynamic relationships were described using non-linear mixed effects modelling. The no-drug effect was constant and all compounds were active in the model, reducing ultrasonic vocalisations immediately after administration. The sigmoid E(max) model was used to describe the pharmacokinetic-pharmacodynamic relationships, with E(max) values of a 90% decrease in baseline ultrasonic vocalisations. Corrected for plasma protein binding, all compounds showed similar potency. The study shows that ultrasonic vocalisations can be considered a suitable endpoint for the anxiolytic effect when used in conjunction with non-linear mixed effects modelling to overcome the limited sampling and effect measurements." @default.
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• W2000436131 date "2001-03-01" @default.
• W2000436131 modified "2023-09-26" @default.
• W2000436131 title "Population pharmacokinetic–pharmacodynamic modelling of S 15535, a 5-HT1A receptor agonist, using a behavioural model in rats" @default.
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• W2000436131 doi "https://doi.org/10.1016/s0014-2999(01)00801-9" @default.
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