Histamine Plays an Important Role in Promoting and Stabilizing Wakefulness1-3

In the brain, histamine acts as a key wake-promoting neurotransmitter1,4

  • Histamine is synthesized in the presynaptic neuron1
  • When released into the synapse, histamine binds to postsynaptic H1 receptors1

Histamine neuronal activity in the brain is modulated by H1 and H3 receptors1

  • H1 receptors increase neuronal activity, which allows for communication with brain regions that are important for sleep and wakefulness1-3
  • H3 receptors are found primarily in the brain and help regulate histamine synthesis and release1,5-7
    • Normally, when histamine levels in the brain are high, histamine binds to presynaptic H3 autoreceptors to inhibit further synthesis and release of histamine in the brain1,5

Hypocretin (orexin) and histamine neurons play complementary roles in the brain8

  • Hypocretin and histamine promote wakefulness by activating the cortex and activating other wake-promoting neurons2,3
  • Hypocretin and histamine also help to stabilize wakefulness by inhibiting non-REM sleep–promoting neurons and REM sleep–promoting neurons1-3
Histamine Neuron Activity image

Loss of hypocretin neurons leads to reduced activation of histamine and other wake-promoting neurons, ultimately resulting in the sleep-wake state instability seen in narcolepsy9,10

The Role of Histamine in Promoting and Stabilizing Wakefulness

Watch this video to learn about the role of histamine in the brain and the importance of histamine in promoting wakefulness.

The Role of Histamine in Promoting Wakefulness video