Pharmacological and microbiological evaluations of potential new long-acting local anaesthetics.
The results of the preliminary pharmacological and microbiological evaluations of certain new derivatives of dialkylaminoethyl-phenyl-ether hydrochloride, as potential long-acting local anaesthetics, are reported. The guinea pig intradermal wheal test was used for determining the activity and duration of local anaesthesia (WT). These were assayed at concentrations of 0.5% w/v. Lidocaine hydrochloride, 1.0% w/v, was employed as the standard and normal saline, 0.9% w/v, as the control. The compounds showed outstanding activity profiles and duration of action with no apparent signs of both local and systemic side effects. In addition, the results of inhibition of the ciliated protozoan Tetrahymena pyriformis mobility by the aforementioned compounds are presented. A general relationship between the minimum inhibitory concentration (MIC) of these compounds to inhibit mobility of the whole T. pyriformis cells and the duration of anaesthesia was observed. Moreover, derivatives with tertiary or secondary butyl substituents in the benzene ring, irrespective of position or number, were superior to others and showed prolonged duration of anaesthesia and lower MIC. The dependence of both WT and MIC on partition coefficient (log P) of these compounds indicates that in both biological systems the anaesthetics interact strongly with hydrophobic structures of the T. pyriformis cells membrane resulting in fluidisation and loss of ciliary function.
al-Saadi
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Department of Pharmacy, School of Pharmacy and Pharmacology, University of Strathclyde, Glasgow, UK.
Sneader
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D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D004048:Diethylamines / Q000494:pharmacology*; D004123:Dimethylamines / Q000494:pharmacology*; D006168:Guinea Pigs; D008826:Microbial Sensitivity Tests; D010147:Pain Measurement; D012867:Skin / Q000187:drug effects; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000648:ultrastructure
D000779:Anesthetics, Local; D004048:Diethylamines; D004123:Dimethylamines