H3- & H4-Receptor Antagonists

H₃- & H₄-RECEPTOR ANTAGONISTS

Although no selective H₃ or H₄ ligands are presently available for general clinical use, there is great interest in their therapeutic potential. H₃-selective ligands may be of value in sleep disorders, narcolepsy, obesity, and cognitive and psychiatric disorders. Tiprolisant, an inverse H₃-receptor agonist, has been shown to reduce sleep cycles in mutant mice and in humans with narco-lepsy. Increased obesity has been demonstrated in both H₁- and H₃-receptor knockout mice. As noted, several newer antipsychotic drugs have significant affinity for H₃ receptors.

Because of the homology between the H₃ and H₄ receptors, many H₃ ligands also have affinity for the H₄ receptor. H₄ blockers have potential in chronic inflammatory conditions such as asthma, in which eosinophils and mast cells play a prominent role. No selective H₄ ligand is available for use in humans, but in addition to research agents listed in Table 16–1, many H₁-selective blockers (eg, diphenhydramine, cetirizine, loratadine) show some affinity for this receptor. Several studies have suggested that H₄-receptor antagonists may be useful in pruritus, asthma, allergic rhinitis, and pain conditions.