Next Article in Journal
An Allosteric Modulator of the Adenosine A1 Receptor Improves Cardiac Function Following Ischaemia in Murine Isolated Hearts
Next Article in Special Issue
Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade
Previous Article in Journal
Disease-Causing Allele-Specific Silencing by RNA Interference
Previous Article in Special Issue
NMDA Receptor Antagonists for Treatment of Depression
Article Menu

Export Article

Open AccessArticle
Pharmaceuticals 2013, 6(4), 536-545; doi:10.3390/ph6040536

Toxicity Studies on Novel N-Substituted Bicyclo-Heptan-2-Amines at NMDA Receptors

1
Department of Biological Sciences, Misher College, University of the Sciences, Philadelphia, PA 19104, USA
2
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA 19104, USA
3
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan 06100, Ankara, Turkey
*
Author to whom correspondence should be addressed.
Received: 25 January 2013 / Revised: 9 April 2013 / Accepted: 9 April 2013 / Published: 12 April 2013
(This article belongs to the Special Issue NMDA Receptor Antagonists for Treatment of CNS Disorders)
View Full-Text   |   Download PDF [1046 KB, uploaded 12 April 2013]   |  

Abstract

Several novel norcamphor derivatives were designed and synthesized as uncompetitive NMDA receptor antagonists at the phencyclidine (PCP) binding site. Such compounds have potential as ligands for understanding and possibly the treatment of several neurodegenerative disorders and other glutamate-dependent disorders. We examined the toxic effects of the compounds as compared with memantine, an NMDA receptor antagonist that is FDA approved for treatment of Alzheimer’s disease, by testing these compounds on two cell lines: MDCK (to mimic blood brain barrier) and N2a (a neuronal cell line). The compounds showed toxicity profiles similar to those of memantine i.e., dose dependence above 100 μM and IC50 values above 150 μM for each cell line. It is known that the serum level of memantine under therapeutic conditions in patients is about 1 µM, indicting these compounds could have acceptable therapeutic indexes. 2-Phenyl-N-(2-(piperidin-1-yl) ethyl)bicyclo[2.2.1]heptan-2-amine (5a) was found to possess acceptable toxicity profiles in both cell lines. Interestingly, this was the compound identified as a good lead in our previous studies based on binding and anticonvulsant (MES) activity studies. It has thus emerged as an excellent lead compound for further studies. View Full-Text
Keywords: NMDA receptor antagonist; neurodegeneration; cytotoxicity; MDCK and N2a cells NMDA receptor antagonist; neurodegeneration; cytotoxicity; MDCK and N2a cells
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Coleman, N.; Ates-Alagoz, Z.; Gaye, B.; Farbaniec, M.; Sun, S.; Adejare, A. Toxicity Studies on Novel N-Substituted Bicyclo-Heptan-2-Amines at NMDA Receptors. Pharmaceuticals 2013, 6, 536-545.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top