Neurobiological Basis of Hypersomnia.

Narcolepsy is the most well-characterized hypersomnia in both clinical and basic research fields. Narcolepsy is caused by degeneration of hypocretin-producing neurons in the hypothalamus. Although hypocretin receptor antagonists have been developed as sleep-inducing drugs, a high dose of suvorexant, a hypocretin receptor antagonist, inhibits gene expression of prepro-hypocretin to induce narcoleptic attack in wild-type mice. Prostaglandin D2 is the most potent endogenous sleep-promoting substance. Overproduction of prostaglandin D2 is involved in hypersomnia in patients with mastocytosis and African sleeping sickness or in mice after a pentylenetetrazole-induced seizure. Commercialized sleep-promoting supplements also may induce hypersomnia in humans.