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.