Abstract
A new series of N-arylalkyl-substituted 7-azabicyclo[2.2.1]heptanes and N-aryl-substituted 7-azabicyclo[2.2.1]heptanes were synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors. The in vitro binding affinities (K(i)) of the 7-azabicyclo[2.2.1]heptane derivatives were measured by inhibition of [(3)H]cytisine binding to rat brain tissue. The most potent ligand of the series was found to be N-(3-pyridylmethyl)-7-azabicyclo[2.2.1]heptane (5b, K(i) = 98 nM). The chloro analogue (5a, K(i) = 245 nM) 5a and epibatidine (1) produced dose-dependent analgesia in both hotplate and tail-flick tests when administered subcutaneously. However, when compounds 1 and 5a,b were administered intrathecally, all produced analgesia in the tail-flick test but only 5a produced analgesia in the hotplate test.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics, Non-Narcotic / chemical synthesis*
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Analgesics, Non-Narcotic / chemistry
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Analgesics, Non-Narcotic / pharmacology
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Animals
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Body Temperature / drug effects
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Brain / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / chemistry*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Crystallography, X-Ray
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Dopamine / metabolism
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In Vitro Techniques
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Injections, Spinal
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Ligands
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Mice
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Nicotinic Agonists / chemical synthesis*
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Nicotinic Agonists / chemistry
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Nicotinic Agonists / pharmacology
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Pain Measurement
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Pyridines / chemistry*
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Nicotinic / metabolism*
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Structure-Activity Relationship
Substances
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Analgesics, Non-Narcotic
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Bridged Bicyclo Compounds, Heterocyclic
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Ligands
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Nicotinic Agonists
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Pyridines
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Receptors, Nicotinic
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epibatidine
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Dopamine