Abstract
A number of 1-arylpiperazines have been characterized as direct-acting serotonin agonists. Conformational parameters of this class that may affect receptor recognition and binding have been examined through the analysis of X-ray data and synthesis of rigid analogues. Radioligand binding studies indicate that 2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino[1,2-a]quinoline, an arylpiperazine that mimics the X-ray conformation of the serotonin agonist 1-(6-chloropyrazin-2-yl)piperazine, exhibits high affinity for serotonin receptors, suggesting that the two rings of 1-arylpiperazines are relatively coplanar in the bioactive conformation.
MeSH terms
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Animals
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Central Nervous System / drug effects
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Central Nervous System / physiology
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Chemical Phenomena
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Chemistry
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Female
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Frontal Lobe / metabolism
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Mice
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Molecular Conformation
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Piperazines / chemical synthesis
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Piperazines / metabolism*
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Piperazines / pharmacology
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Posture
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Pyrazines / chemical synthesis
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Pyrazines / metabolism
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Pyrazines / pharmacology
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Quinolines / chemical synthesis
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Quinolines / metabolism
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Quinolines / pharmacology
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Rats
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Receptors, Serotonin / metabolism*
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Serotonin / metabolism
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Serotonin / pharmacology
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Spiperone / metabolism
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Structure-Activity Relationship
Substances
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Piperazines
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Pyrazines
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Quinolines
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Receptors, Serotonin
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Serotonin
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Spiperone
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6-chloro-2-(1-piperazinyl)pyrazine
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2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino(1,2-a)quinoline