Enerisant

Enerisant is an experimental drug under investigation as a potential treatment for narcolepsy. It is a member of the histamine H₃ receptor antagonist/inverse agonist class of medications.

Pharmacology

Pharmacodynamics

Enerisant functions as a potent and highly selective antagonist/inverse agonist of the histamine H₃ receptor. This mechanism of action is similar to that of pitolisant, 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. By blocking H₃ receptors, enerisant increases histamine release from histaminergic neurons, leading to stimulation of postsynaptic histamine H₁ receptors, a key mechanism in promoting wakefulness

Pharmacokinetics

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.