Open AccessProcognitive Properties of Drugs with Single and Multitargeting H 3 Receptor Antagonist Activities
Author(s) -
Nikolic Katarina,
Filipic Slavica,
Agbaba Danica,
Stark Holger
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12279
Subject(s) - histamine h3 receptor , histaminergic , inverse agonist , pharmacology , chemistry , neurotransmission , pharmacophore , 5 ht6 receptor , 5 ht receptor , serotonin , neuroscience , histamine , receptor , antagonist , psychology , medicine , biochemistry
Summary The histamine H 3 receptor (H 3 R) is an important modulator of numerous central control mechanisms. Novel lead optimizations for H 3 R antagonists/inverse agonists involved studies of structure–activity relationships, cross‐affinities, and pharmacokinetic properties of promising ligands. Blockade of inhibitory histamine H 3 autoreceptors reinforces histaminergic transmission, while antagonism of H 3 heteroreceptors accelerates the corticolimbic liberation of acetylcholine, norepinephrine, glutamate, dopamine, serotonin and gamma‐aminobutyric acid (GABA). The H 3 R positioned at numerous neurotransmission crossroads indicates therapeutic applications of small‐molecule H 3 R modulators in a number of psychiatric and neurodegenerative diseases with various clinical candidates available. Dual target drugs displaying H 3 R antagonism/inverse agonism with inhibition of acetylcholine esterase (AChE), histamine N‐methyltransferase (HMT), or serotonin transporter (SERT) are novel class of procognitive agents. Main chemical diversities, pharmacophores, and pharmacological profiles of procognitive agents acting as H 3 R antagonists/inverse agonists and dual H 3 R antagonists/inverse agonists with inhibiting activity on AChE, HMT, or SERT are highlighted here.