Abstract
We investigated the pharmacological profile of a novel series of quinoxaline-based 5-HT(3) receptor ligands bearing an extra basic moiety on the piperazine N-4. High affinity and selectivity were dependent on the electronic properties of the substituents, and at cardiac level 3a and 3c modulated chronotropy but not inotropy. In von Bezold-Jarisch reflex test 3a-c were partial agonists while 3i was a full agonist. Preliminary pharmacokinetic studies indicated that 3a is a brain penetrating agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood-Brain Barrier / metabolism
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Drug Partial Agonism
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Guinea Pigs
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Heart Rate / drug effects
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In Vitro Techniques
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Ligands
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Myocardial Contraction / drug effects
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology
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Quinoxalines / chemical synthesis*
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Quinoxalines / pharmacokinetics
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Quinoxalines / pharmacology
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Rats
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Reflex / drug effects
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Serotonin 5-HT3 Receptor Agonists*
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Serotonin 5-HT3 Receptor Antagonists
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Structure-Activity Relationship
Substances
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Ligands
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Pyrroles
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Quinoxalines
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Serotonin 5-HT3 Receptor Agonists
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Serotonin 5-HT3 Receptor Antagonists