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Synthesis and electrophysiological studies of a novel epibatidine analogue.
Journal article

Synthesis and electrophysiological studies of a novel epibatidine analogue.

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  • 1999-03-11
Published in:
  • Journal of receptor and signal transduction research. - 1999
Animals
Bridged Bicyclo Compounds, Heterocyclic
Electrophysiology
Female
In Vitro Techniques
Nicotinic Agonists
Oocytes
Pyridines
Rats
Receptors, Nicotinic
Recombinant Proteins
Stereoisomerism
Structure-Activity Relationship
Xenopus laevis
English The new epibatidine analogue exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane (2PABH) was synthesised. Separation of enantiomers was performed on chiral HPLC chromatography in polar-organic phase mode at 0 degree C. Enantiomeric purity was greater than 99.8%ee for the (-)- and 90.5%ee for the (+)-enantiomer respectively. Optical rotation was determined to be [alpha]23D = +/- 13 degrees. Electrophysiological studies of 2PABH were carried out on alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes cloned from rat and reconstituted in Xenopus oocytes. Both enantiomers could not significantly activate the heteromeric subtypes. The homomeric alpha 7 nAChR displays a high sensitivity only towards (-)-2PABH. The EC50 for (-)-2PABH and ACh were determined (32.5 +/- 9.5 microM, 137.3 +/- 16.5 microM). (-)-2PABH was shown to be a partial agonist (80% of ACh). Thus the efficacy of 2PABH differs markedly from that of epibatidine. The intramolecular N-N-distance and the spatial pyridine nitrogen orientation play a central role in nAChR recognition.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/132416
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