OPIOID PHARMACOLOGY OF THE ANTINOCICEPTIVE EFFECTS OF LOPERAMIDE IN MICE
OPIOID PHARMACOLOGY OF THE ANTINOCICEPTIVE EFFECTS OF LOPERAMIDE IN MICE
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DOI：
10.1097/00008877-199404000-00010
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发表时间：
1994-04-01
影响因子：
1.6
通讯作者：
WOODS, JH
中科院分区：
文献类型：
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作者：
TAKASUNA, M;NEGUS, SS;WOODS, JH
洛哌丁胺（0.1-3.2 mg/kg i. p.）在醋酸诱导的小鼠扭体试验中产生剂量依赖性和完全的扭体抑制。纳洛酮（NTX; 0.1-10.0 mg/kg s.c.）及其N-甲基化衍生物季纳洛酮（QNTX; 1.0和10.0 mg/kg s.c.）在拮抗洛哌丁胺的抗伤害作用方面大致等效。相比之下，NTX在拮抗经典μ激动剂吗啡的抗伤害效应方面比QNTX强约100倍。此外，洛哌丁胺的抗伤害感受作用未被选择性μ拮抗剂D-Phe Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH 2（CTAP; 300 ng i. c. v.）的中枢给药拮抗，或通过全身施用κ选择性拮抗剂去甲-binaltorphimine（去甲-BNI; 32.0 mg/kg s.c.），或δ拮抗剂纳曲吲哚（NTI; 10.0 mg/kg s.c.）。这些剂量的CTAP、nor-BNI和NTI分别是吗啡、κ激动剂U69，593和δ激动剂BW 373 U86 [（+/-）-4-（（R*）-α-（（2S* 5 R *）-4-烯丙基-2，5-二甲基-1-哌嗪醛）-3-羟基苄基）-N，N-二乙基苯甲酰胺二盐酸盐]的有效拮抗剂。这些结果表明，洛哌丁胺在小鼠中的镇痛作用至少部分由阿片受体介导;然而，这些受体与介导吗啡、U69、593和BW 373 U86作用的阿片受体不同。这些结果与洛哌丁胺至少部分通过作用于外周阿片受体而产生抗伤害感受作用的假设一致。
Loperamide (0.1-3.2 mg/kg i.p.) produced dose-dependent and complete suppression of writhing in the acetic acid-induced writhing assay in mice. Naltrexone (NTX; 0.1-10.0 mg/kg s.c.) and its N-methylated derivative quaternary naltrexone (QNTX; 1.0 and 10.0 mg/kg s.c.) were roughly equipotent in antagonizing the antinociceptive effects of loperamide. In contrast, NTX was approximately 100-fold more potent than QNTX in antagonizing the antinociceptive effects of the classical mu agonist morphine. Furthermore, the antinociceptive effects of loperamide were not antagonized by central administration of the selective mu antagonist D-Phe Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 300 ng i.c.v.), or by systemic administration of either the kappa selective antagonist nor-binaltorphimine (nor-BNI; 32.0 mg/kg s.c.), or the delta antagonist naltrindole (NTI; 10.0 mg/kg s.c.). These doses of CTAP, nor-BNI and NTI were effective antagonists of morphine, the kappa agonist U69,593 and the delta agonist BW 373U86 [(+/-)-4-((R*)-a-((2S*5R*)-4-allyl-2,5-dimethyl-1-piperazinal)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride], respectively. These results indicate that the antinociceptive effects of loperamide in mice are mediated, at least in part, by opioid receptors; however, these receptors are distinct from the opioid receptors mediating the effects of morphine, U69,593 and BW 373U86. These results are consistent with the hypothesis that loperamide produces its antinociceptive effects by acting, at least in part, at peripheral opioid receptors.