The Antinociceptive Activity of (E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide in Mice Is Reduced by (E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide Through Opposing Modulatory Mechanisms at the α7 Nicotinic Acetylcholine Receptor.

ABSTRACT:

Background

The primary objective of this study was to characterize the pharmacological and behavioral activity of 2 novel compounds, DM497 [(E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide] and DM490 [(E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide], structural derivatives of PAM-2, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (nAChR).

Methods

A mouse model of oxaliplatin-induced neuropathic pain (2.4 mg/kg, 10 injections) was used to test the pain-relieving properties of DM497 and DM490. To assess possible mechanisms of action, the activity of these compounds was determined at heterologously expressed α7 and α9α10 nAChRs, and voltage-gated N-type calcium channel (Ca V 2.2) using electrophysiological techniques.

Results

Cold plate test

SUBMITTER: Arias HR 

PROVIDER: S-EPMC10408732 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature