Enerisant (INNTooltip International Nonproprietary Name; developmental code nameTS-091) is an experimental drug under investigation as a potential treatment fornarcolepsy. It is a member of thehistamine H3 receptor antagonist/inverse agonist class of medications.[1][2][3]
Enerisant functions as a potent and highly selective antagonist/inverse agonist of thehistamine H3 receptor. This mechanism of action is similar to that ofpitolisant, a currently approved H3 receptor antagonist/inverse agonist for narcolepsy; however, enerisant has demonstrated greater affinity and selectivity for the H3 receptor in preclinical studies.[1][2][3][4][5] By blocking H3 receptors, enerisant increases histamine release from histaminergic neurons, leading to stimulation of postsynaptichistamine H1 receptors, a key mechanism in promoting wakefulness[1][3][4]
Enerisant exhibits minimal metabolism in humans and is primarily eliminated unchanged via renal excretion. After oral administration, it rapidly absorbs and exhibits dose-dependent plasma concentrations. Within 48 hours, 64.5-89.9% of the administered dose is recovered unchanged in urine. Plasma protein binding is approximately 31.0–31.7% in humans.[1][5]
^abWalker NA, Vaughn BV (17 February 2023). "Update on Randomized Controlled Trials in CNS Hypersomnias".Current Sleep Medicine Reports.9 (2):101–109.doi:10.1007/s40675-023-00249-6.ISSN2198-6401.
