Synthesis and structure-activity relationship studies of theophylline analogs on population responses in the rat hippocampus in vitro

Kethireddy V V Ananthalakshmi; Tomás Bartl; Mohammed H Aziza; Ladislav Novotný; Radek Marek; Ludek Benes; Samuel B Kombian

doi:10.1016/j.bmc.2008.07.045

Synthesis and structure-activity relationship studies of theophylline analogs on population responses in the rat hippocampus in vitro

Bioorg Med Chem. 2008 Sep 1;16(17):8142-50. doi: 10.1016/j.bmc.2008.07.045. Epub 2008 Jul 23.

Authors

Kethireddy V V Ananthalakshmi¹, Tomás Bartl, Mohammed H Aziza, Ladislav Novotný, Radek Marek, Ludek Benes, Samuel B Kombian

Affiliation

¹ Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.

PMID: 18676148
DOI: 10.1016/j.bmc.2008.07.045

Abstract

We synthesized several theophylline analogs and tested the hypothesis that these compounds may be nootropic or cognitive enhancers by examining their effects on evoked population spikes recorded extracellularly in the CA1 region of the rat hippocampus. Whereas the length of the carbon chain on N7 had no effect, different size of the terminal lactam ring strongly influenced neuroactivity. Our results suggest that hexahydroazepin-2-one analogs have potential for further development as cognitive enhancers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Animals
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Electrodes
Hippocampus / cytology
Hippocampus / drug effects*
Hippocampus / physiology
Male
Molecular Structure
Neurons / classification
Neurons / drug effects*
Neurons / physiology
Nootropic Agents / chemical synthesis*
Nootropic Agents / pharmacology*
Rats
Rats, Sprague-Dawley
Stereoisomerism
Structure-Activity Relationship
Theophylline / analogs & derivatives
Theophylline / chemical synthesis*
Theophylline / pharmacology*
Time Factors

Substances

Nootropic Agents
Theophylline