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Fraction unbound in plasma (fu,p) of drugs is an significant factor for drug delivery and other biological incidences related to the pharmacokinetic behaviours of drugs. Exploration of different molecular fragments for fu,p of different small molecules/agents can facilitate in identification of suitable candidates in the preliminary stage of drug discovery. Different researchers have implemented strategies to build several prediction models for fu,p of different drugs. However, these studies did not focus on the identification of responsible molecular fragments to determine the fraction unbound in plasma. In the current work, we tried to focus on the development of robust classification-based QSAR models and evaluated these models with multiple statistical metrics to identify essential molecular fragments/structural attributes for fractions unbound in plasma. The study unequivocally suggests various N-containing aromatic rings and aliphatic groups have positive influences and sulphur-containing thiadiazole rings have negative influences for the fu,p values. The molecular fragments may help for the assessment of the fu,p values of different small molecules/drugs in a speedy way in comparison to experiment-based in vivo and in vitro studies. [ABSTRACT FROM AUTHOR]

P2X receptor function in the CNS is poorly understood, and currently available data are partly inconsistent. In the presented study, we investigated P2X 3 receptors stably expressed in HEK293 cells. Non-stationary noise analysis of whole cell currents and rapid ATP application through flash photolysis allowed for assessing the single channel conductance (6.6  pS) and the fast activation kinetics of the receptor (20  ms). The characteristics of channel desensitization and pharmacological properties matched previous findings. The properties of wild type receptors were compared with P2X 3 constructs carrying a fluorescent tag (ECFP or DsRed 2 ) at the C-terminus. These fluorescently labeled subunits formed functional receptors, with neither the affinity of the ligand binding site nor channel properties (ion selectivity, gating kinetics, single channel conductance) differing from wild type. We conclude that both fusion proteins tested here are suitable for generating transgenic mice, which can be expected to promote understanding of the physiological role of P2X 3 receptors in CNS signaling. [ABSTRACT FROM AUTHOR]