title: The alpha2-adrenergic agonist guanfacine reduces excitability of human motor cortex through disfacilitation and increase of inhibition.
abstract: OBJECTIVE
  To test the acute effects of the alpha2-adrenoceptor agonist guanfacine (GFC) on motor excitability in intact humans.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D004574:Electromagnetic Fields; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects; D016316:Guanfacine / Q000494:pharmacology*; D006801:Humans; D008280:Magnetics; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects*; D012684:Sensory Thresholds; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D016316:Guanfacine