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N-油酰多巴胺可降低利血平诱导的大鼠肌肉强直。

N-oleoyl-dopamine decreases muscle rigidity induced by reserpine in rats.

作者信息

Konieczny J, Przegalinski E, Pokorski M

机构信息

Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.

出版信息

Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):21-8. doi: 10.1177/039463200902200104.

Abstract

N-oleoyl-dopamine (OLDA), a product of condensation of oleic acid and dopamine (DA), is a bioactive compound that crosses the blood-brain barrier after systemic administration. The possibility arises that OLDA could have a potential role in treating DA-related disorders, such as Parkinsons disease (PD). In the present study we seek to determine whether OLDA would affect muscle tone and akinesia in two rat models of PD: the reserpine-evoked muscle rigidity and the reserpine- and haloperidol-induced catalepsy. We found that OLDA (20 mg/kg) significantly decreased muscle rigidity induced by reserpine (2.5 mg/kg), measured as an increased mechanical muscle resistance (MMG) in response to a passive extension and flexion of a rat hind limb at the ankle joint. Moreover, OLDA potently decreased the reserpine-enhanced tonic and reflex electromyographic (EMG) activities recorded before and during the movement, respectively. A lower dose of OLDA (10 mg/kg) failed to have appreciable effects. The reference compound L-DOPA (25 mg/kg) also attenuated the reserpine-increased MMG and EMG activities; the effects were, however, observed much later and were less prominent than those characteristic of OLDA. In contrast to the effects on muscle tone, OLDA (20 and 40 mg/kg) did not influence catalepsy induced by either reserpine (1.25 mg/kg) or haloperidol (0.5 mg/kg). In conclusion, the study demonstrates a novel biological action of N-oleoyl-dopamine consisting of lowering the reserpine-induced muscle rigidity. However, the lack of influence on akinesia suggests that the compound has myorelaxant rather than anti-Parkinsonian properties.

摘要

N-油酰多巴胺(OLDA)是油酸与多巴胺(DA)缩合的产物,是一种生物活性化合物,全身给药后可穿过血脑屏障。因此,OLDA有可能在治疗与DA相关的疾病(如帕金森病(PD))中发挥潜在作用。在本研究中,我们试图确定OLDA是否会影响两种PD大鼠模型的肌张力和运动不能:利血平诱发的肌肉僵硬以及利血平和氟哌啶醇诱导的僵住症。我们发现,OLDA(20mg/kg)显著降低了利血平(2.5mg/kg)诱导的肌肉僵硬,通过测量大鼠后肢踝关节被动屈伸时机械肌肉阻力(MMG)的增加来评估。此外,OLDA分别有效降低了运动前和运动过程中记录的利血平增强的强直和反射性肌电图(EMG)活动。较低剂量的OLDA(10mg/kg)没有明显效果。参比化合物左旋多巴(L-DOPA,25mg/kg)也减弱了利血平增加的MMG和EMG活动;然而,其效果出现得更晚,且不如OLDA显著。与对肌张力的影响相反,OLDA(20mg/kg和40mg/kg)对利血平(1.25mg/kg)或氟哌啶醇(0.5mg/kg)诱导的僵住症没有影响。总之,该研究证明了N-油酰多巴胺的一种新的生物学作用,即降低利血平诱导的肌肉僵硬。然而,对运动不能缺乏影响表明该化合物具有肌松作用而非抗帕金森病特性。

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