Analgesic activity of two synthetic immunomodulators, muramyl dipeptide and adamantylamide dipeptide in mice and rats.
Analgesic activity of two synthetic immunomodulators, muramyl dipeptide and adamantylamide dipeptide in mice and rats.
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两种合成免疫调节剂胞壁酰二肽和金刚酰胺二肽对小鼠和大鼠的镇痛活性。
DOI：
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发表时间：
1988
影响因子：
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通讯作者：
K. Mašek
中科院分区：
文献类型：
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作者：
P. Horák;K. Mašek
研究了两种人工合成的免疫调节剂胞壁酰二肽和金刚烷酰胺二肽对痛阈的免疫佐剂和免疫调节作用。采用小鼠和大鼠热板法和醋酸扭体法两种不同的扭体方法。静脉内（1-4 mg/kg）、腹膜内（5-50 mg/kg）和脑室内（0.5-4 mg/kg）注射两种化合物，在两种物种中均能产生轻度一过性镇痛。全身给药对扭体反应的影响较大，而热板灌肠对扭体反应的影响较小。而侧脑室给药后，热板法对扭体反应的影响大于扭体反应。剂量反应曲线显示肽的典型钟形特征。用纳洛酮（一种阿片拮抗剂）预处理并不能阻止受试化合物的镇痛作用。给药非镇痛剂量的MDP（0.025 mg/kg）可预防5-羟色胺耗竭剂对氯苯丙氨酸引起的痛觉过敏。在较高剂量（1 mg/kg）下，MDP也能够拮抗pCPA的一般毒性作用。这些结果支持了中枢神经系统参与MDP和AdDP镇痛的可能性。然而，不能完全排除外周作用机制。
The potency of two synthetic immunomodulators, muramyl dipeptide and adamantylamide dipeptide, which have the immunoadjuvant and immunomodulatory activity on pain threshold was studied. Two different analgesiometric procedures were employed: hot plate test and acetic acid writhing test in mice and rats. Both compounds were injected intravenously (1-4 mg/kg), intraperitoneally (5-50 mg/kg) and intracerebroventricularly (0.5-4 mg/kg) and were able to produce mild transient analgesia in both species. Writhing response was more influenced after systemic administration of drugs while hot plate latencies was not. On the contrary, latencies in hot plate test were more affected than the writhing response after intracerebroventricular administration. Dose response curve showed a bell shaped feature typical for peptides. Pretreatment with naltrexone, an opiate antagonist, did not prevent the analgesic action of tested compounds. The hyperalgesia induced by administration of parachlorophenylalanine, a serotonin depletor, could be prevented by administration of a nonanalgesic dose of MDP (0.025 mg/kg). At higher dosages (1 mg/kg) MDP was able to antagonize also general toxic effects of pCPA. These results support the possibility of participation of central serotonergic structures in MDP and AdDP induced analgesia. The peripheral mechanism of action, however, can not be completely ruled out.