Déciga-Campos Myrna, Navarrete-Vázquez Gabriel, López-Muñoz Francisco Javier, Librowski Tadeusz, Sánchez-Recillas Amanda, Yañez-Pérez Victor, Ortiz-Andrade Rolffy
Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México.
Facultad de Farmacia de la Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
Life Sci. 2016 Jun 15;155:48-55. doi: 10.1016/j.lfs.2016.05.015. Epub 2016 May 12.
N-(2,6-Dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide (LIA), a lidocaine analogue, has potential applications in treating neuropathic pain. The aim of this work was to characterize the pharmacological activity of LIA related with central nervous system and cardiovascular activity.
Anesthetic effect was tested in guinea pigs and mice. Ambulatory activity, anti-anxiety effect, sodium pentobarbital (PB)-induced hypnosis and pentylenetetrazol (PTZ)-induced seizures test were evaluated in mice to determine the possible central nervous system activity. The cardiovascular activities in vivo and ex vivo were analyzed in rats.
LIA (2%) presents, similar to lidocaine (2%), anesthetic activity on the corneal reflex, infiltration anesthesia and tail immersion test. LIA (1-100mg/kg, i.p.), similar to lidocaine (1-100mg/kg, i.p.), presents a dose-dependent sedative-hypnotic effect in mice. Both compounds did not produce anti-anxiety activity in mice. LIA did not prevent PTZ-induced seizures. However, LIA itself did not produce seizures at high doses in mice, as lidocaine does. LIA is a vasorelaxant compound for smooth muscle cells and presents hypotensive effect in vivo without increments to the heart rate significantly.
High doses of lidocaine produce seizures and vasoconstriction. In this study, we found that LIA shares a similar pharmacological profile as lidocaine's but without the primary adverse effects of seizures and vasoconstriction.
N-(2,6-二氯苯基)-2-(4-甲基-1-哌啶基)乙酰胺（LIA），一种利多卡因类似物，在治疗神经性疼痛方面具有潜在应用。本研究的目的是表征LIA与中枢神经系统和心血管活性相关的药理活性。
在豚鼠和小鼠中测试麻醉效果。在小鼠中评估自主活动、抗焦虑作用、戊巴比妥钠（PB）诱导的催眠和戊四氮（PTZ）诱导的惊厥试验，以确定可能的中枢神经系统活性。在大鼠中分析体内和体外的心血管活性。
LIA（2%）与利多卡因（2%）类似，对角膜反射、浸润麻醉和尾浸试验具有麻醉活性。LIA（1-100mg/kg，腹腔注射）与利多卡因（1-100mg/kg，腹腔注射）类似，在小鼠中呈现剂量依赖性的镇静催眠作用。两种化合物在小鼠中均未产生抗焦虑活性。LIA不能预防PTZ诱导的惊厥。然而，与利多卡因不同，LIA本身在高剂量时不会在小鼠中引发惊厥。LIA是一种平滑肌细胞血管舒张化合物，在体内具有降压作用，且心率无明显增加。
高剂量利多卡因会引发惊厥和血管收缩。在本研究中，我们发现LIA与利多卡因具有相似的药理特征，但没有惊厥和血管收缩等主要不良反应。
