Nabiximols (NBX) suppresses tremor in a rat Harmaline model of essential tremor

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-10-04 DOI:10.1016/j.expneurol.2024.114988

Sally Loomis, Elena Samoylenko, David Virley, Andrew C. McCreary

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引用次数: 0

Abstract

Background

Essential tremor (ET) is one of the most prevalent movement disorders; despite this, there remains an unmet need for novel therapies. The treatment of rats with harmaline modulates the rhythmicity of inferior olivary neurons, resulting in generalized tremor with a frequency of 9–12 Hz in rats, comparable to that of human ET (4–12 Hz).

Purpose

Interestingly, cannabinoids reduce tremor, therefore we have assessed the cannabinoid nabiximols (NBX; marketed as Sativex) a complex botanical drug mixture, in the harmaline-rat model of ET.

Method

We tested the effects of acute (single dose) and subchronic (10 days) treatment of NBX (at 5.2, 10.4 and 20.8 mg kg⁻¹ p.o.) administered prior to harmaline and acute NBX (20.8 mg kg⁻¹) administered post-harmaline in male SD rats. Propranolol (20 mg kg⁻¹ i.p.) was used as a positive control. Observed Scoring (OS) was carried out prior to placement in a tremor-monitoring apparatus for the calculation of Tremor Index (TI) and Motion Power Percentage (MPP).

Results

Acute and subchronic NBX significantly attenuated harmaline-induced tremor at 10.4 and 20.8 mg kg⁻¹, respectively, for each parameter (OS, TI, and MPP) when administered pre-harmaline as did propranolol (20 mg kg⁻¹). NBX did not attenuate harmaline-induced tremor when administered post-harmaline.

Conclusions

These data suggest efficacy of acute and subchronic NBX to reduce tremors, based on OS, TI and MPP readouts if administered prior to harmaline. These data are the first to indicate the preclinical effects of an oral botanical cannabinoid formulation, NBX, in an animal model of ET.

Abstract Image

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Nabiximols (NBX) 可抑制大鼠 Harmaline 本质性震颤模型中的震颤。

背景：本质性震颤（ET）是最常见的运动障碍之一；尽管如此，对新型疗法的需求仍未得到满足。目的：有趣的是，大麻素能减少震颤，因此我们评估了大麻素 nabiximols（NBX；市场名为 Sativex）--一种复合植物药混合物--在哈马林-大鼠 ET 模型中的作用：我们以雄性 SD 大鼠为研究对象，测试了在服用哈马林之前急性（单剂量）和亚慢性（10 天）服用 NBX（5.2、10.4 和 20.8 毫克/公斤-1 p.o.）以及在服用哈马林之后急性服用 NBX（20.8 毫克/公斤-1）的效果。普萘洛尔（20 毫克/千克-1 毫升）作为阳性对照。在将大鼠放入震颤监测仪器前进行观察评分（OS），以计算震颤指数（TI）和运动力百分比（MPP）：急性和亚慢性 NBX 与普萘洛尔（20 毫克/千克-1）一样，分别以 10.4 毫克/千克-1 和 20.8 毫克/千克-1 的剂量显著减轻肝素诱发的震颤。在服用哈马林后服用 NBX 不会减轻哈马林引起的震颤：这些数据表明，根据OS、TI和MPP读数，急性和亚慢性NBX对减少震颤有疗效，如果在服用哈马林之前给药的话。这些数据首次表明了口服植物大麻素制剂 NBX 在 ET 动物模型中的临床前效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.