author={Seiji Nishino and Emmanuel Jean-Marie Mignot},
  journal={Progress in Neurobiology},

Narcolepsy: Neuropharmacological Aspects

Clinical and pharmacological aspects of narcolepsy as well as future directions are discussed.

Clinical and neurobiological aspects of narcolepsy.

Challenges in the development of therapeutics for narcolepsy

The pathogenesis of narcolepsy, current treatments and prospective therapeutic targets

Development of synthetic hypocretin receptor agonists is the first and most urgent step for the improved treatment of Type 1 narcolepsy and will likely lead to developments of cell transplantation and gene therapies.

Overview of Management of Narcolepsy

Clinical symptoms of narcolepsy are described, and the state-of-the-art knowledge about both pharmacological and non-pharmacological treatments ofNarcoleptic patients is reviewed.

Narcolepsy: new understanding of irresistible sleep.

The current understanding of the diagnosis and treatment of narcolepsy is reviewed and the possible implications of the hypocretin discovery are discussed.

Hypocretin/orexin and narcolepsy: new basic and clinical insights

As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.



Neuropharmacology and neurochemistry of canine narcolepsy.

It is demonstrated that cholinoceptive sites in the pontine reticular formation, as well as in the basal forebrain, are involved in the regulation of cataplexy, suggesting that a widespread hyperactivity of cholinergic systems within the central nervous system together with a hypoactivity of catecholaminergic systems underlie the pathophysiology of narcolepsy.

Dopamine D2 mechanisms in canine narcolepsy

  • S. NishinoJ. Arrigoni E. Mignot
  • Psychology, Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1991
Using a canine model of the disease, it is found that central D2 antagonists suppressed cataplexy, a form of REM-sleep atonia occurring in narcolepsy, whereas this symptom was aggravated by D2 agonists, suggesting that the effect of D2 compounds on catapLexy is mediated secondarily via the noradrenergic systems.

Muscle atonia is triggered by cholinergic stimulation of the basal forebrain: implication for the pathophysiology of canine narcolepsy

  • S. NishinoM. Tafti E. Mignot
  • Biology, Psychology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
Results suggest that a cholinoceptive site in the BF is critically implicated in triggering muscle atonia and cataplexy, and it appears that a widespread hypersensitivity to cholinergic stimulation may be central to the pathophysiology of canine narcolepsy.

Monoaminergic mechanisms and experimental cataplexy

The suppression of cataplexy induced by nisoxetine or protriptyline was reversed by the anticholinesterase physostigmine, further supporting a postulated aminergic‐cholinergic interaction in the mechanisms for catAPlexy.

Role of central alpha-1 adrenoceptors in canine narcolepsy.

It is shown that the beneficial effects of classical treatments of human narcolepsy 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).

Narcolepsy-cataplexy in a female dog.

The nature of the narcoleptic sleep attack

For many years, narcolepsy has been regarded as a sleep abnormality and it is assumed that knowledge pertaining to normal sleep mechanisms will aid in understanding the pathophysiology of the illness.

Neuronal activity in narcolepsy: identification of cataplexy-related cells in the medial medulla.

The data demonstrate that cataplexy is a distinct behavioral state, differing from other sleep and waking states in its pattern of brainstem neuronal activity.

Physiology of REM sleep, cataplexy, and sleep paralysis.

The main neural structures generating muscle atonia and other phenomena characteristic of REM sleep are present in dorsolateral portions of the pons in the brainstem, and this last monoaminergic neuronal population probably has a gating or inhibiting effect upon the cholinergic and cholinoceptive neuronal populations related to the generation of generalized Muscle atonia in REM sleep.