Mignot E, Guilleminault C, Bowersox S, Rappaport A, Dement W C
Sleep Disorders Center, Stanford University School of Medicine, Palo Alto, California 94304.
J Clin Invest. 1988 Sep;82(3):885-94. doi: 10.1172/JCI113694.
The role of central alpha-1 adrenergic receptors in cataplexy was investigated in genetically narcoleptic Doberman pinschers. Treatment of narcoleptic dogs with 25-600 micrograms/kg prazosin, a selective alpha-1 adrenergic receptor blocker, exacerbated cataplexy, whereas treatment with the alpha-1 agonist, methoxamine, ameliorated it. Subsequent studies showed that the beneficial effects of classical treatments of human narcolepsy (amphetamines and tricyclic antidepressants) are antagonized by prazosin, suggesting that these drugs are active through an indirect alpha-1 stimulation (via an increase of norepinephrine in the synaptic cleft). Other studies confirmed that the observed effects were not due to peripheral alpha-1 cardiovascular involvement. Atropine, a central anticholinergic agent, but not methylatropine, a peripheral one, completely suppressed the prazosin effect, which suggests that adrenergic and cholinergic systems act sequentially and not independently to generate cataplexy. Little is known about the physiological role of central alpha-1 adrenoceptors. This series of experiments implicates these receptors in narcolepsy-cataplexy.
在遗传性发作性睡病的杜宾犬中，研究了中枢α-1肾上腺素能受体在猝倒症中的作用。用25-600微克/千克哌唑嗪（一种选择性α-1肾上腺素能受体阻滞剂）治疗发作性睡病犬，会使猝倒症恶化，而用α-1激动剂甲氧明治疗则可改善猝倒症。随后的研究表明，人类发作性睡病的经典治疗药物（苯丙胺和三环类抗抑郁药）的有益作用会被哌唑嗪拮抗，这表明这些药物是通过间接的α-1刺激（通过增加突触间隙中的去甲肾上腺素）发挥作用的。其他研究证实，观察到的效应并非由于外周α-1对心血管的影响。中枢抗胆碱能药物阿托品可完全抑制哌唑嗪的作用，而外周抗胆碱能药物甲基阿托品则不能，这表明肾上腺素能和胆碱能系统在产生猝倒症时是依次作用而非独立作用的。关于中枢α-1肾上腺素能受体的生理作用知之甚少。这一系列实验表明这些受体与发作性睡病-猝倒症有关。
