Valeri P, Morrone L A, Romanelli L, Amico M C
Institute of Pharmacology and Pharmacognosy, University of Rome La Sapienza, Italy.
J Pharmacol Exp Ther. 1993 Mar;264(3):1028-32.
The inhibition mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs) on withdrawal response was examined in vitro. Naloxone elicited a strong contraction in the isolated guinea pig ileum after a 5-min exposure of the tissue to morphine. The contraction was inhibited by aspirin, indomethacin and salicylic acid, administered concomitantly to morphine or 1 min before the opioid antagonist. The short contact time of NSAIDs with the isolated preparations seems to indicate that mechanisms other than inhibition of prostaglandins synthesis are implicated in this action. NSAIDs depressed the ileum contraction to naloxone after stimulation of the tissue with cholecystokinin, when injected into the bath 1 min before the peptide. The contraction to naloxone after exposure to indirect excitatory peptides was very similar to withdrawal contraction. After maximal ileum stimulation with prostaglandin E1, naloxone induced a strong contraction indicating that this substance activates the opioid system, as occurs with cholecystokinin. NSAIDs, at concentrations that inhibit naloxone-induced contractions, did not depress the maximal contracture to cholecystokinin and prostaglandin E1, but inhibited the submaximal one. These results suggest that the inhibition of withdrawal contraction by NSAIDs in acute dependence is due mainly to their ability to block the contraction caused by substances whose action is neuronally mediated, which are released to counteract the opioid action. Prostaglandin E1 may be part of this system of action and reaction.
在体外研究了非甾体抗炎药（NSAIDs）对戒断反应的抑制机制。在将组织暴露于吗啡5分钟后，纳洛酮可引起离体豚鼠回肠强烈收缩。阿司匹林、吲哚美辛和水杨酸与吗啡同时给药或在阿片类拮抗剂给药前1分钟给药，可抑制该收缩。NSAIDs与离体制剂的接触时间较短，这似乎表明除了抑制前列腺素合成之外的其他机制也参与了这一作用。当在肽给药前1分钟注入浴槽时，NSAIDs在用胆囊收缩素刺激组织后可抑制回肠对纳洛酮的收缩。暴露于间接兴奋性肽后对纳洛酮的收缩与戒断收缩非常相似。在用前列腺素E1对回肠进行最大刺激后，纳洛酮诱导强烈收缩，表明该物质激活了阿片系统，胆囊收缩素的情况也是如此。NSAIDs在抑制纳洛酮诱导的收缩的浓度下，并未抑制对胆囊收缩素和前列腺素E1的最大挛缩，但抑制了次最大挛缩。这些结果表明，NSAIDs在急性依赖中对戒断收缩的抑制主要是由于它们能够阻断由神经介导作用的物质引起的收缩，这些物质被释放以对抗阿片类药物的作用。前列腺素E1可能是这个作用和反应系统的一部分。
