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.^[1][2][3]

Enerisant

Clinical data
Other names	TS-091
Routes of administration	By mouth
Pharmacokinetic data
Protein binding	31.0–31.7%[1]
Elimination half-life	8 hours[1]
Excretion	Kidney (64.5–89.9%)[1]
Identifiers
IUPAC name [1-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone
CAS Number	1152747-82-4
PubChem CID	42601503
IUPHAR/BPS	11293
ChemSpider	44208825
UNII	E2Y97PQY3A
Chemical and physical data
Formula	C22H30N4O3
Molar mass	398.507 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1CCCN1CCCOC2=CC=C(C=C2)N3C=C(C=N3)C(=O)N4CCOCC4
InChI InChI=1S/C22H30N4O3/c1-18-4-2-9-24(18)10-3-13-29-21-7-5-20(6-8-21)26-17-19(16-23-26)22(27)25-11-14-28-15-12-25/h5-8,16-18H,2-4,9-15H2,1H3/t18-/m1/s1 Key:IABXVJILZYNSTM-GOSISDBHSA-N

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.^{[1][2][3][4][5]} 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^[1][3][4]

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.^[1][5]