Brown M J, Struthers A D, di Silvio L
J Cardiovasc Pharmacol. 1985;7 Suppl 6:S159-61. doi: 10.1097/00005344-198500076-00027.
Guanfacine 3 mg was infused into six volunteers over 1 h on two occasions to investigate whether its sympatholytic effect is centrally or peripherally mediated. On one occasion, the central effects of guanfacine were blocked by prior administration of idazoxan 0.2 mg/kg i.v. (45 min preguanfacine); central alpha 2-blockade was confirmed by inhibition of the guanfacine-induced rise in plasma growth hormone. Rapid disappearance of idazoxan from the circulation prevented antagonism of peripheral alpha 2 receptor effects of guanfacine (confirmed by suppression of plasma insulin by guanfacine on both occasions). Idazoxan elevated plasma noradrenaline concentration by 0.26 +/- 0.018 ng/ml; however, guanfacine caused a similar (approximately 30%) reduction in plasma noradrenaline after both idazoxan and vehicle. Idazoxan elevated systolic and diastolic blood pressure, but no change was observed after guanfacine on either occasion. Thus, the reduction in plasma noradrenaline caused by guanfacine appears to be peripherally mediated but is not due to baroreceptor activation. This is consistent with stimulation of presynaptic alpha 2 receptors.
在六名志愿者身上分两次在1小时内静脉输注3毫克胍法辛，以研究其抗交感神经作用是由中枢介导还是外周介导。一次，在静脉注射0.2毫克/千克伊达唑嗪（在胍法辛前45分钟）后，胍法辛的中枢作用被阻断；通过抑制胍法辛诱导的血浆生长激素升高来确认中枢α2受体阻滞。伊达唑嗪从循环中快速消失，从而无法拮抗胍法辛的外周α2受体效应（两次均通过胍法辛抑制血浆胰岛素来确认）。伊达唑嗪使血浆去甲肾上腺素浓度升高0.26±0.018纳克/毫升；然而，在注射伊达唑嗪和赋形剂后，胍法辛均使血浆去甲肾上腺素产生类似的（约30%）降低。伊达唑嗪使收缩压和舒张压升高，但在两种情况下，注射胍法辛后均未观察到血压变化。因此，胍法辛引起的血浆去甲肾上腺素降低似乎是由外周介导的，但并非由于压力感受器激活。这与突触前α2受体的刺激一致。
