Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors.
Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors.
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DOI：
10.1007/s00213-009-1513-8
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发表时间：
2009-07
影响因子：
3.4
通讯作者：
Del Pozo, Esperanza
中科院分区：
文献类型：
--
作者：
Entrena, Jose M.;Cobos, Enrique J.;Nieto, Francisco R.;Cendan, Cruz M.;Baeyens, Jose M.;Del Pozo, Esperanza
关键词：
我们评价了氟哌啶醇及其代谢物对辣椒素诱导的小鼠机械超敏反应(痛敏)和点状机械刺激引起的伤害性疼痛的影响。皮下注射氟哌啶醇或其代谢物I或II(还原氟哌啶醇)可剂量依赖性地逆转辣椒素(1 μg，足底内)所致的机械超敏反应(用0.5g的无痛刺激，点状刺激)。这些药物的抗痛觉过敏效应的强弱顺序是它们与脑σ-1受体([~3H](+)-五唑碱标记的)的亲和力顺序。选择性σ-1受体激动剂Pre-084可剂量依赖性地抑制氟哌啶醇及其代谢物的抗痛觉过敏活性，但纳洛酮对其无明显影响。这些结果提示σ-1受体参与了抗痛觉过敏的作用，但忽略了内源性阿片系统的任何作用。多巴胺受体拮抗似乎也不太可能参与这些作用，因为D2/D3受体拮抗剂(−)舒必利与σ1受体没有亲和力，没有抗痛觉过敏作用。在非辣椒素敏感的动物中，这些药物都不能改善在痛苦的(4g力)点状机械刺激后后爪的收缩。正如预期的那样，对照药物加巴喷丁显示出抗痛觉过敏的活性，而可乐定显示了这两种活性，而作为阴性对照的罗非昔布则没有显示出这两种活性。这些结果表明，氟哌啶醇及其代谢物I和II对点状机械刺激有止痛作用，但不产生止痛作用，提示其抗痛觉过敏作用可能是通过阻断σ-1受体而不是通过拮抗多巴胺受体来实现的。
We evaluated the effects of haloperidol and its metabolites on capsaicin-induced mechanical hypersensitivity (allodynia) and on nociceptive pain induced by punctate mechanical stimuli in mice. Subcutaneous administration of haloperidol or its metabolites I or II (reduced haloperidol) dose-dependently reversed capsaicin-induced (1 μg, intraplantar) mechanical hypersensitivity of the hind paw (stimulated with a nonpainful, 0.5-g force, punctate stimulus). The order of potency of these drugs to induce antiallodynic effects was the order of their affinity for brain sigma-1 (σ1) receptor ([3H](+)-pentazocine-labeled). Antiallodynic activity of haloperidol and its metabolites was dose-dependently prevented by the selective σ1 receptor agonist PRE-084, but not by naloxone. These results suggest the involvement of σ1 receptors, but discard any role of the endogenous opioid system, on the antiallodynic effects. Dopamine receptor antagonism also appears unlikely to be involved in these effects, since the D2/D3 receptor antagonist (−)-sulpiride, which had no affinity for σ1 receptors, showed no antiallodynic effect. None of these drugs modified hind-paw withdrawal after a painful (4 g force) punctate mechanical stimulus in noncapsaicin-sensitized animals. As expected, the control drug gabapentin showed antiallodynic but not antinociceptive activity, whereas clonidine exhibited both activities and rofecoxib, used as negative control, showed neither. These results show that haloperidol and its metabolites I and II produce antiallodynic but not antinociceptive effects against punctate mechanical stimuli and suggest that their antiallodynic effect may be due to blockade of σ1 receptors but not to dopamine receptor antagonism.
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影响因子：
7.4
作者：
Gilchrist, HD;Allard, BL;Simone, DA
通讯作者：
Simone, DA
影响因子：
5
作者：
Honkaniemi, J;Liimatainen, S;Sulavuori, S
通讯作者：
Sulavuori, S
影响因子：
5.3
作者：
Cobos EJ;Entrena JM;Nieto FR;Cendán CM;Del Pozo E
通讯作者：
Del Pozo E
影响因子：
2.3
作者：
Bermack, JE;Debonnel, G
通讯作者：
Debonnel, G
影响因子：
2.3
作者：
Cobos, EJ;Baeyens, JM;Del Pow, E
通讯作者：
Del Pow, E