Enerisant

Last updated

Enerisant
Enerisant.svg
Clinical data
Other namesTS-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
  • [1-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
Chemical and physical data
Formula C22H30N4O3
Molar mass 398.507 g·mol−1
3D model (JSmol)
  • C[C@@H]1CCCN1CCCOC2=CC=C(C=C2)N3C=C(C=N3)C(=O)N4CCOCC4
  • 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 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]

Contents

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]

References

  1. 1 2 3 4 5 6 7 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. 1 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. 1 2 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. 1 2 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.{{cite journal}}: CS1 maint: article number as page number (link)
  5. 1 2 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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