H3 receptor antagonist

An H₃-receptor antagonist is a classification of drugs used to block the action of histamine at the H₃ receptor. Unlike the H₁ and H₂ receptors which have primarily peripheral actions, but cause sedation if they are blocked in the brain, H₃ receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H₁ receptors in the cerebral cortex. Consequently, unlike the H₁ antagonist antihistamines which are sedating, H₃ antagonists have stimulant and nootropic effects, and are being researched as potential drugs for the treatment of neurodegenerative conditions such as Alzheimer's disease.

Examples of selective H₃ antagonists include clobenpropit, ABT-239, ciproxifan, Conessine, A-349,821, and pitolisant.