Korchounov Alexei, Ilić Tihomir V, Ziemann Ulf
Clinic of Neurology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, D-60590, Frankfurt, Germany.
Clin Neurophysiol. 2003 Oct;114(10):1834-40. doi: 10.1016/s1388-2457(03)00192-5.
To test the acute effects of the alpha2-adrenoceptor agonist guanfacine (GFC) on motor excitability in intact humans.
Eight healthy right-handed adults received a single oral dose of 2 mg of GFC. Motor cortex excitability was tested by focal transcranial magnetic stimulation of the hand area of the left motor cortex. Motor evoked potentials (MEP) were recorded from the right abductor pollicis brevis muscle. In addition, spinal and neuromuscular excitability were tested. All measures were obtained immediately before GFC intake (baseline), and 2, 6, and 24 h later.
GFC decreased the slope of the MEP intensity curve, increased paired-pulse short-interval intracortical inhibition, and decreased paired-pulse intracortical facilitation and I-wave facilitation. These effects were maximal at 2-6 h and returned to baseline at 24 h. Motor threshold, cortical silent period, and the measures of spinal (peripheral silent period, F waves) and neuromuscular excitability (maximum M wave) remained unaffected.
This is the first study on the effects of an anti-noradrenergic drug on human motor cortex excitability. GFC reduced cortical excitability by disfacilitation and increased inhibition. These findings support the idea that anti-noradrenergic drugs are detrimental for cortical plasticity and learning which are down-regulated by disfacilitation or increased inhibition.
测试α2肾上腺素能受体激动剂胍法辛（GFC）对完整人体运动兴奋性的急性影响。
8名健康的右利手成年人单次口服2毫克GFC。通过对左侧运动皮层手部区域进行局灶性经颅磁刺激来测试运动皮层兴奋性。从右侧拇短展肌记录运动诱发电位（MEP）。此外，还测试了脊髓和神经肌肉兴奋性。所有测量均在摄入GFC前（基线）以及2、6和24小时后进行。
GFC降低了MEP强度曲线的斜率，增加了双脉冲短间隔皮质内抑制，并降低了双脉冲皮质内易化和I波易化。这些效应在2至6小时时最大，并在24小时时恢复到基线水平。运动阈值、皮质静息期以及脊髓（外周静息期、F波）和神经肌肉兴奋性（最大M波）的测量值均未受影响。
这是第一项关于抗去甲肾上腺素能药物对人体运动皮层兴奋性影响的研究。GFC通过去易化作用降低了皮质兴奋性并增加了抑制作用。这些发现支持了抗去甲肾上腺素能药物对皮质可塑性和学习有害的观点，而去易化或增加抑制作用会下调皮质可塑性和学习。
