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Enerisant

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Pharmaceutical compound
Enerisant
Clinical data
Other namesTS-091
Routes of
administration		By mouth
Pharmacokinetic data
Protein binding31.0–31.7%
Elimination half-life8 hours
ExcretionKidney (64.5–89.9%)
Identifiers
IUPAC name
  • propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC22H30N4O3
Molar mass398.507 g·mol
3D model (JSmol)
SMILES
  • C1CCCN1CCCOC2=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

Enerisant is an experimental histamine H3 receptor antagonist/inverse agonist being investigated as a potential treatment for sleep-wake disorders, particularly narcolepsy.

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.

References

  1. ^ Terasaka S, Hachiuma K, Mano Y, Onishi K, Kitajima I, Nishino I, Endo H (July 2021). "Drug-drug interaction potential and clinical pharmacokinetics of enerisant, a novel potent and selective histamine H3 receptor antagonist". Xenobiotica. 51 (7): 786–795. doi:10.1080/00498254.2021.1918361. PMID 33910470.
  2. ^ Klaus S, Carolan A, O'Rourke D, Kennedy B (September 2022). "What respiratory physicians should know about narcolepsy and other hypersomnias". Breathe (Sheffield, England). 18 (3): 220157. doi:10.1183/20734735.0157-2022. PMC 9973529. PMID 36865656.
  3. ^ Inoue Y, Uchiyama M, Umeuchi H, Onishi K, Ogo H, Kitajima I, Matsushita I, Nishino I, Uchimura N (February 2022). "Optimal dose determination of enerisant (TS-091) for patients with narcolepsy: two randomized, double-blind, placebo-controlled trials". BMC Psychiatry. 22 (1): 141. doi:10.1186/s12888-022-03785-7. PMC 8862520. PMID 35193545.
  4. ^ Alhusaini M, Eissa N, Saad AK, Beiram R, Sadek B (2022). "Revisiting Preclinical Observations of Several Histamine H3 Receptor Antagonists/Inverse Agonists in Cognitive Impairment, Anxiety, Depression, and Sleep-Wake Cycle Disorder". Frontiers in Pharmacology. 13: 861094. doi:10.3389/fphar.2022.861094. PMC 9198498. PMID 35721194.
  5. ^ Walker 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. ISSN 2198-6401.
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