Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Alcorcón, Spain.
Neurogastroenterol Motil. 2019 Aug;31(8):e13621. doi: 10.1111/nmo.13621. Epub 2019 May 22.
Loperamide is a potent mu opioid receptor agonist available over the counter to treat diarrhea. Although at therapeutic doses loperamide is devoid of central effects, it may exert them if used at high doses or combined with drugs that increase its systemic and/or central bioavailability. Recently, public health and scientific interest on loperamide has increased due to a growing trend of misuse and abuse, and consequent reports on its toxicity. Our aim was to evaluate in the rat the effects of increasing loperamide doses, with increasing likelihood to induce central effects, on gastrointestinal motor function (including gastric dysmotility and nausea-like behavior).
Male Wistar rats received an intraperitoneal injection of vehicle or loperamide (0.1, 1, or 10 mg kg ). Three sets of experiments were performed to evaluate: (a) central effects (somatic nociceptive thresholds, immobility time, core temperature, spontaneous locomotor activity); (b) general gastrointestinal motility (serial X-rays were taken 0-8 hours after intragastric barium administration and analyzed semiquantitatively, morphometrically, and densitometrically); and (c) bedding intake (a rodent indirect marker of nausea). Animals from sets 1 and 3 were used to evaluate gastric dysmotility ex vivo at 2 and 4 hours after administration, respectively.
Loperamide significantly induced antinociception, hypothermia, and hypolocomotion (but not catalepsy) at high doses and dose-dependently reduced gastrointestinal motor function, with the intestine exhibiting higher sensitivity than the stomach. Whereas bedding intake occurred early and transiently, gastric dysmotility was much more persistent.
Our results suggest that loperamide-induced nausea and gastric dysmotility might be temporally dissociated.
洛哌丁胺是一种有效的μ阿片受体激动剂，可在柜台上购买用于治疗腹泻。尽管在治疗剂量下，洛哌丁胺没有中枢作用，但如果高剂量使用或与增加其全身和/或中枢生物利用度的药物联合使用，它可能会发挥作用。最近，由于滥用和误用的趋势不断增加，以及关于其毒性的报告不断增加，公众健康和科学界对洛哌丁胺的兴趣日益增加。我们的目的是在大鼠中评估增加洛哌丁胺剂量（增加诱导中枢作用的可能性）对胃肠道运动功能（包括胃动力障碍和类似恶心的行为）的影响。
雄性 Wistar 大鼠接受腹腔注射载体或洛哌丁胺（0.1、1 或 10mg/kg）。进行了三组实验来评估：（a）中枢作用（躯体疼痛阈值、不动时间、核心体温、自发运动活动）；（b）一般胃肠道动力（胃内钡剂给药后 0-8 小时进行系列 X 射线检查，并进行半定量、形态计量和密度计量分析）；和（c）卧床摄入（一种啮齿动物恶心的间接标志物）。第 1 组和第 3 组的动物分别在给药后 2 小时和 4 小时用于评估胃动力障碍的离体实验。
洛哌丁胺在高剂量下显著诱导镇痛、体温降低和运动减少（但不引起僵住），并剂量依赖性地降低胃肠道动力功能，肠道的敏感性高于胃。尽管卧床摄入发生较早且短暂，但胃动力障碍更为持久。
我们的结果表明，洛哌丁胺引起的恶心和胃动力障碍可能在时间上有所分离。
