Effects of a novel neurotensin peptide analog given extracranially on CNS behaviors mediated by apomorphine and haloperidol
Effects of a novel neurotensin peptide analog given extracranially on CNS behaviors mediated by apomorphine and haloperidol
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DOI：
10.1016/s0006-8993(99)02363-x
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发表时间：
2000-02-21
期刊：
影响因子：
2.9
通讯作者：
Richelson, E
中科院分区：
文献类型：
--
作者：
Cusack, B;Boules, M;Richelson, E
神经紧张素（NT）是中枢神经系统中的一种神经肽神经递质。它与抗精神病药的治疗作用和不良反应有关。脑内NT的活性只能通过直接向该器官注射肽来显示。然而，我们已经开发出一种新的NT（8-13）类似物NT69L，它在腹腔注射后具有活性。与非典型神经阻滞剂一样，NT69L对大鼠攀爬行为有抑制作用，但对高剂量（600 μ g/kg）非选择性多巴胺激动剂阿波啡的舔和嗅行为无抑制作用。其对攀爬的阻断非常有效，ED50（最大有效剂量的50%）为16 μ g/kg。阿波啡和NT69L均可引起持久的低体温，与肽联用时低体温更大，但与阿波啡联用时无协同作用。NT69L对低温的ED为390 μ g/kg。NT69L（高达5 mg/kg i.p）不会产生眩晕。然而，在氟哌啶醇之前给予，NT69L，而不是氯氮平，完全预防了猝倒。氟哌啶醇后给药，NT69L，而不是氯氮平，逆转氟哌啶醇的催化作用，ED50为260 μ g/kg。低体温与NT69L抗癫痫作用的ED(50)s无显著差异。然而，阻断阿波啡作用的ED50明显低于其他两种。这些数据表明，NT69L可能对人类具有抗精神病药物的特性，并可用于治疗由氟哌啶醇等典型抗精神病药物引起的锥体外系副作用。(C) 2000 Elsevier Science B.V.版权所有
Neurotensin (NT) is a neuropeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic and in the adverse effects of neuroleptics. Activity of NT in brain can only be shown by direct injection of the peptide into that organ. However, we have developed a novel analog of NT(8-13), NT69L, which is active upon intraperitoneal (i.p.) injection. Like atypical neuroleptics, NT69L blocked the climbing behavior in rats, but not the licking and sniffing behaviors of a high close (600 mu g/kg) of the non-selective dopamine agonist apomorphine. Its blockade of climbing was very potent with an ED50 (effective dose at 50% of maximum) of 16 mu g/kg. Both apomorphine and NT69L caused a long-lasting hypothermia, which was greater with the peptide bur nor synergistic in combination with apomorphine. The ED,, of NT69L for hypothermia was 390 mu g/kg. NT69L (up to 5 mg/kg i.p.) did nut produce catalepsy. However, when given before haloperidol, NT69L, but not clozapine, completely prevented catalepsy. When given after haloperidol, NT69L, but not clozapine, reversed haloperidol's cataleptic effects with an ED50 of 260 mu g/kg. There was no significant difference between the ED(50)s for hypothermia and anticataleptic effects of NT69L. However, the ED50 for blocking the effects of apomorphine was significantly lower than the other two. These data suggest that NT69L may have neuroleptic properties in humans and may be useful in the treatment of extrapyramidal side effects caused by typical neuroleptics such as haloperidol. (C) 2000 Elsevier Science B.V. All rights reserved.