Abstract
The novel 8-piperazinyl-2,3-dihydropyrroloisoquinoline template was synthesized in nine steps. The template was N-substituted to give a series of compounds showing binding to human cloned 5-HT1A, 5-HT1B and 5-HT1D receptors with pKi's greater than 9 and selectivities up to 1000-fold against other serotonin, dopamine and adrenergic receptors. Several compounds were shown to possess weak partial agonist activity in cloned receptors, which translated to antagonism in in vitro studies.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Brain Chemistry
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Isoquinolines / chemical synthesis*
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Isoquinolines / pharmacokinetics
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Isoquinolines / pharmacology
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Ligands
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Rats
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Receptor, Serotonin, 5-HT1A
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Receptor, Serotonin, 5-HT1B
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Receptor, Serotonin, 5-HT1D
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Receptors, Serotonin / drug effects*
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / pharmacokinetics
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / chemical synthesis*
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Serotonin Receptor Agonists / pharmacokinetics
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Serotonin Receptor Agonists / pharmacology
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Structure-Activity Relationship
Substances
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Isoquinolines
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Ligands
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Receptor, Serotonin, 5-HT1B
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Receptor, Serotonin, 5-HT1D
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Receptors, Serotonin
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Receptor, Serotonin, 5-HT1A