Abstract
In this study, the piperidine ring of immepip and its analogues was replaced by a rigid heterocyclic pyridine ring. Many compounds in the series exhibit high affinity and agonist activity at the human histamine H(3) receptor. Particularly, the 4-pyridinyl analogue of immepip (1c, immethridine) is identified as a novel potent and highly selective histamine H(3) receptor agonist (pK(i) = 9.07, pEC(50) = 9.74) with a 300-fold selectivity over the closely related H(4) receptor.
MeSH terms
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Animals
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Cell Line
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Guinea Pigs
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Histamine Agonists / chemical synthesis*
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Histamine Agonists / chemistry
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Histamine Agonists / pharmacology
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Humans
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Ileum / drug effects
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Ileum / innervation
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Ileum / physiology
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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In Vitro Techniques
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Myenteric Plexus / drug effects
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Myenteric Plexus / physiology
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Radioligand Assay
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Receptors, Histamine H3 / drug effects*
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Receptors, Histamine H3 / metabolism
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Structure-Activity Relationship
Substances
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Histamine Agonists
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Imidazoles
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Pyridines
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Receptors, Histamine H3