Abstract
The terminal nitrogen atom of histamine was modified with lipophilic substituents to investigate the structure-activity relationship of histamine type 3 receptor (H3R) agonists. The introduction of an alkylated benzene rings maintained or increased the H3R binding affinity. The most potent compound, 4-(2-(4-tert-butylphenylthio)ethyl)-1H-imidazole, possessed in vivo agonistic activity, decreasing brain N(tau)-methylhistamine levels in mice after oral administration. It also exhibited antistress activity in the mouse resident-intruder test.
MeSH terms
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Administration, Oral
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Animals
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Brain Chemistry
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Histamine / analogs & derivatives*
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Histamine / chemistry
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Histamine Agonists / chemistry*
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Histamine Agonists / metabolism
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Histamine Agonists / therapeutic use
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Hydrophobic and Hydrophilic Interactions
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Methylhistamines / analysis
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Mice
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Receptors, Histamine / metabolism
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Receptors, Histamine H3 / drug effects
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Receptors, Histamine H3 / metabolism*
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Stress, Psychological / drug therapy
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Stress, Psychological / prevention & control
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Structure-Activity Relationship
Substances
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Histamine Agonists
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Methylhistamines
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Receptors, Histamine
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Receptors, Histamine H3
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Histamine