Evaluation of -Aminocarboxylic Acid Derivatives in Hippocampal Excitatory Synaptic Transmission

Author(s)

Oliveira, Daniela R. ^[1] ; Luchez, Cibele V. ^[2] ; Bortolotto, Zuner A. ^[1] ; Fernandes, Joao P. S. ^[2]

Affiliation

^[1] Univ Bristol, Ctr Synapt Plast, Sch Physiol Pharmacol & Neurosci, Bristol, Avon - England

^[2] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

• Document type: Journal article
• Source: ARCHIV DER PHARMAZIE; v. 350, n. 11 NOV 2017.
• Web of Science Citations: 0

Abstract

-Aminocarboxylic acid derivatives (LINS04 series) were screened with the aim to explore their potential functional role in excitatory synaptic transmission in the central nervous system. We used field recordings in rat hippocampal slices to investigate the effects of the LINS04 series on the synaptic transmission at hippocampal CA1 synapses. We found that LINS04008 and LINS04009 increase the size of the evoked field excitatory postsynaptic potential (EPSP) in a dose-dependent manner. The concentration-response curve shows that the efficacy of LINS04008 is highest in the series (EC50=91.32 mu M; maximum fEPSP 44.97%). The esters LINS04006 and LINS04005 did not affect the synaptic evoked activity. These data provide the first evidence of synaptic activity enhancement by these compounds and the importance of the acidic group to the activity. This set of data may provide direction for a strategic procedure to restore the glutamate synaptic transmission; however, further studies are needed to establish a more complete picture of how these molecules act on the glutamate transmission, which are in our mind for the next steps. (AU)

• FAPESP's process: 13/20479-9 - Synthesis and evaluation of compounds potentially ligands of H4 receptors
• Grantee: João Paulo dos Santos Fernandes
• Support Opportunities: Regular Research Grants