Kirkpatrick A F, Lavallee-Grey M, Haynes D H
Department of Anesthesiology, University of South Florida College Medicine, Tampa 33612-4799.
Reg Anesth. 1991 May-Jun;16(3):164-72.
Lecithin-coated microdroplets of methoxyflurane (MOF) are shown to produce local anesthesia of three- to six-day duration in the skin with a single intradermal injection in rats. Anesthesia was quantitated by elevation of the threshold (milliampere) for shock vocalization with intradermal electrodes. Intradermal injection of 0.1 ml 0.5% MOF gave moderate (2.1 mA) anesthesia of approximately three-day duration for a 10-12-mm diameter area, with no damage to the tissue. Higher concentrations gave six-day duration anesthesia at very high level (7 to 12 mA) anesthesia of three- to five-day duration with some damage to the tissue. At 4.4% MOF, ulcers formed in the center of the injection site with maximal dimensions of 1.3 mm (11-13% of the site diameter). Phenol, a widely used neurolytic agent, was tested as a control in the same concentration range. Phenol at 4.4% gave very high level (8 mA) anesthesia for longer than seven-day duration and caused formation of ulcers with maximal dimensions of 3.8 mm (31-38% of the site diameter). Analysis showed that MOF produced less damage than phenol for any given degree of anesthesia. Systemic toxicity and pharmacokinetic data are also presented. Phenol produced a hypothermic reaction and behavioral changes, whereas MOF was without systemic effect. The plasma concentrations of phenol were four to five times greater than those of MOF. These results suggest that MOF may have clinical advantages over phenol.
在大鼠中，通过单次皮内注射，甲氟醚（MOF）的卵磷脂包被微滴可在皮肤中产生持续三到六天的局部麻醉。通过皮内电极提高电击发声阈值（毫安）来定量麻醉效果。皮内注射0.1 ml 0.5%的MOF可在直径10 - 12毫米的区域产生约三天持续时间的中度（2.1毫安）麻醉，且对组织无损伤。更高浓度可产生六天持续时间的麻醉，在三到五天持续时间内达到非常高的水平（7至12毫安），对组织有一些损伤。在4.4%的MOF浓度下，注射部位中心形成溃疡，最大尺寸为1.3毫米（占部位直径的11 - 13%）。苯酚是一种广泛使用的神经溶解剂，在相同浓度范围内作为对照进行测试。4.4%的苯酚可产生超过七天持续时间的非常高的水平（8毫安）麻醉，并导致形成最大尺寸为3.8毫米（占部位直径的31 - 38%）的溃疡。分析表明，在任何给定的麻醉程度下，MOF对组织的损伤都比苯酚小。还给出了全身毒性和药代动力学数据。苯酚会产生体温过低反应和行为变化，而MOF无全身作用。苯酚的血浆浓度比MOF高四到五倍。这些结果表明，与苯酚相比，MOF可能具有临床优势。
