Materials and methods.The experiments were performed in the dorsal skin of 6 male guinea-pigs (Charles River) 250-350 g of weight according to the methods of Bülbring & Wada (1953) and Henn (1960). In short, dorsal skin was shaved with an electric shaver 24 hours before experiments. Depiled skin was divided in 3 areas and a small surface in each area was ink-labelled. 0.1 ml of test solutions (mepivacaine 1%, IQB-9302 1% or saline) were intradermically injected.Five minutes after administration, marked surfaces were stimulated for six consecutive times with a hypodermic needle, and stimulus were repeated at 5 minutes intervals for one hour. Positive responses, evidenced by contraction of dorsal muscles with lateral displacement of the skin, such denoting the absence of anesthesia, were recorded and percentage of anesthesia was calculated. In a second series of experiments made one week apart, 4 male guinea-pigs were injected with mepivacaine 1%, IQB-9302 0.5% and IQB-9302 0.1% RESULTSFigure 3 shown the results of the first set of experiments and figure 4 the results of the second series.Mepivacaine exhibited its maximum effect 5 minutes after intradermal injection and no response to stimulus were observed up to 10 minutes. Afterwards, anesthetic effects slowly decreased and disappeared 55 minutes after dosing. IQB-9302 1% exhibited 100% anesthesia up to 50 min and, being higher than 90% at the end of experiments. Moreover, when IQB-9302 was injected at 0.5% and 0.1% concentrations, complete and long lasting anaesthetic effects were shown for the whole duration of the experiments (90% anaesthesia at 60 minutes after IQB-9302 0.1% injection). From these series of experiments it can be concluded that IQB-9302 is more than 10 times more potent than mepivacaine in the infiltration anesthesia tests. |
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