caa a22 4500 477126766 CHVBK 20180405111652.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012119527214 doi (NATIONALLICENCE)springer-10.1023/A:1012119527214 Chromatographic Indexes on Immobilized Artificial Membranes for Local Anesthetics: Relationships with Activity Data on Closed Sodium Channels [Elektronische Daten] [Francesco Barbato, Maria La Rotonda, Fabiana Quaglia] Purpose. To elucidate the effectiveness of the different parameters for the prediction of biological activity, the n-octanol/buffer partition coefficients and theoretical calculated lipophilicity parameters of thirteen local anesthetic drugs (LAs), including two β-blockers, were compared to the affinity values for phospholipids, calculated by a recent technique. Methods. Interactions with phospholipids were measured by high performance liquid chromatography on a stationary phase made up of phospholipids, the so-called 'Immobilized Artificial Membrane' (IAM). Reference lipophilicity parameters were measured by shake-flask method between n-octanol and buffer phases. Results. Interactions with phospholipids were predicted from log P for all compounds except tocainide, which also showed additive polar extra-interactions. Moreover, when the retention on Immobilized Artificial Membrane (IAM) phase was mainly lipophilicity-based, a unique scale included the correlation between log kw IAM and log P values, for both LAs (bases) and the structurally unrelated (nonionizable and acidic) compounds previously studied. IAM interaction values for LAs were predictive of the partition measures on liposome membranes already reported in literature. The half-blocking doses for closed sodium channel, corrected for ionization at pH 7.4, were successfully correlated with the respective IAM values for eleven compounds while procaine and tetracaine, which are ester-linked compounds and have a p-amino group as well, gave more potent results than predicted by phospholipid interactions. Conclusions. The IAM chromatographic parameters were much more effective than reference lipophilicity values in describing partition on model membranes and in predicting pharmacological potency on closed sodium channels. Plenum Publishing Corporation, 1997 local anesthetics nationallicence HPLC nationallicence immobilized artificial membrane (IAM) nationallicence sodium channels nationallicence Barbato Francesco Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltá di Farmacia, Universitá degli Studi di Napoli 'Federico II'—, Via Domenico Montesano, 49 80131, Naples, Italy aut La Rotonda Maria Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltá di Farmacia, Universitá degli Studi di Napoli 'Federico II'—, Via Domenico Montesano, 49 80131, Naples, Italy aut Quaglia Fabiana Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltá di Farmacia, Universitá degli Studi di Napoli 'Federico II'—, Via Domenico Montesano, 49 80131, Naples, Italy aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1699-1705 0724-8741 14:12<1699 1997 14 11095 https://doi.org/10.1023/A:1012119527214 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012119527214 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Barbato Francesco Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltá di Farmacia, Universitá degli Studi di Napoli 'Federico II'—, Via Domenico Montesano, 49 80131, Naples, Italy aut NATIONALLICENCE 700 1- La Rotonda Maria Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltá di Farmacia, Universitá degli Studi di Napoli 'Federico II'—, Via Domenico Montesano, 49 80131, Naples, Italy aut NATIONALLICENCE 700 1- Quaglia Fabiana Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltá di Farmacia, Universitá degli Studi di Napoli 'Federico II'—, Via Domenico Montesano, 49 80131, Naples, Italy aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1699-1705 0724-8741 14:12<1699 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer