title: Adenosine presynaptic inhibition and transmitter "spillover": a new hypothesis of etiopathogenesis of narcolepsy.
abstract: Neurobiologic and clinical evidence has been discussed in order to propose a new hypothesis explaining the precipitous nature of narcoleptic attacks. It is postulated that narcoleptic episodes are triggered by a surge in the tone of the arousal system which temporarily overcomes the abnormal tonic inhibitory influences of adenosine on presynaptic terminals of the arousal system. As a result, abnormally high levels of accumulated transmitters "spillover" onto supersensitive postsynaptic receptors both in the brain and spinal cord. Such a state reduces the tone of the skeletal muscles and blocks the thalamo-cortical association system, causing a hypnagogic state incompatible with adaptive and cognitive functions. An agent selectively blocking A1 receptors would constitute the most appropriate treatment of narcolepsy. In theory, the hereditary predisposition toward narcolepsy could be corrected by perinatal treatment with an agonist of A1 receptors, thus causing an enduring down-regulation of the genome expression that regulates the ontogeny and proliferation of the A1 receptors.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
authors.forename: T J
authors.initials: TJ
authors.lastname: Marczynski
mesh_terms: D000110:Acetylcholinesterase / Q000502:physiology; D000241:Adenosine / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009290:Narcolepsy / Q000209:etiology* / Q000235:genetics; D009638:Norepinephrine / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D011983:Receptors, Purinergic; D000110:Acetylcholinesterase; D000241:Adenosine; D009638:Norepinephrine