Therapeutic Potential of Histamine H3 Receptors in Substance Use Disorders

Ciano, Patricia Di; Hendershot, Christian S.; Foll, Bernard Le

doi:10.1007/7854_2022_372

Cited by 4 publications

(1 citation statement)

References 82 publications

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“…In particular, as an inhibitory heteroreceptor, H 3 R can affect the level of some neurotransmitters, such as serotonin, norepinephrine, γ-aminobutyric acid, and glutamate in the CNS related to epilepsy [7][8][9]. It has been proved that H 3 R antagonists can treat epilepsy by promoting the synthesis and secretion of histamine [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Antiseizure Properties of Histamine H3 Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones

Song

Guo

et al. 2023

Molecules

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H3R is becoming an attractive and promising target for epilepsy treatment as well as the discovery of antiepileptics. In this work, a series of 6-aminoalkoxy-3,4-dihydroquinolin-2(1H)-ones was prepared to screen their H3R antagonistic activities and antiseizure effects. The majority of the target compounds displayed a potent H3R antagonistic activity. Among them, compounds 2a, 2c, 2h, and 4a showed submicromolar H3R antagonistic activity with an IC50 of 0.52, 0.47, 0.12, and 0.37 μM, respectively. The maximal electroshock seizure (MES) model screened out three compounds (2h, 4a, and 4b) with antiseizure activity. Meanwhile, the pentylenetetrazole (PTZ)-induced seizure test gave a result that no compound can resist the seizures induced by PTZ. Additionally, the anti-MES action of compound 4a fully vanished when it was administrated combined with an H3R agonist (RAMH). These results showed that the antiseizure role of compound 4a might be achieved by antagonizing the H3R receptor. The molecular docking of 2h, 4a, and PIT with the H3R protein predicted their possible binding patterns and gave a presentation that 2h, 4a, and PIT had a similar binding model with H3R.

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