Abstract
S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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3,4-Dihydroxyphenylacetic Acid / metabolism
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8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
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Adenylyl Cyclase Inhibitors
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Adenylyl Cyclases / metabolism
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Animals
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Anti-Anxiety Agents / pharmacology
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Behavior, Animal / drug effects
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Binding, Competitive
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Body Temperature Regulation / drug effects
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Bradycardia / chemically induced
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Bradycardia / prevention & control
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Colforsin / pharmacology
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Dopamine / metabolism
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Dose-Response Relationship, Drug
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Guinea Pigs
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HeLa Cells
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Humans
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Hydroxyindoleacetic Acid / metabolism
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Hypothalamus / drug effects
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Hypothalamus / metabolism
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Ileum / drug effects
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Ileum / physiology
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In Vitro Techniques
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Male
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Membrane Potentials / drug effects
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Mice
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Motor Activity / drug effects
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Muscle Contraction / drug effects
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Neurons / drug effects
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Neurons / physiology
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Piperazines / metabolism*
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Piperazines / pharmacology
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Pyrazines / metabolism*
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Pyrazines / pharmacology
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Radioligand Assay
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Raphe Nuclei / cytology
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Raphe Nuclei / drug effects
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Raphe Nuclei / physiology
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Rats
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Rats, Sprague-Dawley
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Rats, Wistar
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Receptor, Serotonin, 5-HT1A / genetics
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Receptor, Serotonin, 5-HT1A / metabolism
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Receptor, Serotonin, 5-HT2A / metabolism
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Receptors, Serotonin / metabolism*
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Receptors, Serotonin, 5-HT3 / metabolism
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Serotonin / analogs & derivatives*
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Serotonin / metabolism
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Serotonin / pharmacology
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Serotonin / toxicity
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Serotonin Receptor Agonists / pharmacology
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Social Behavior
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Transfection
Substances
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2-((4-(naphth-1-yl)piperazin-1-yl)methyl)-1,4-dioxoperhydropyrrolo(1,2-a)pyrazine
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Adenylyl Cyclase Inhibitors
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Anti-Anxiety Agents
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Piperazines
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Pyrazines
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT3
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Serotonin Receptor Agonists
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3,4-Dihydroxyphenylacetic Acid
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Receptor, Serotonin, 5-HT1A
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Colforsin
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Serotonin
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Hydroxyindoleacetic Acid
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2-methyl-5-HT
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Adenylyl Cyclases
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Dopamine