D. Criddle, Ana Vanesca P. Meireles, Liana B. Macêdo
Feb 1, 2002
Citations
1
Influential Citations
12
Citations
Quality indicators
Journal
Journal of Pharmacy and Pharmacology
Abstract
Novel derivatives of 2‐[3‐(trifluoromethyl)‐analino]nicotinic acid (niflumic acid) were synthesized. The compounds were compared for their inhibitory effects on 5‐hydroxytryptamine (5‐HT)‐ and KCl‐induced contraction of the rat fundus. The aim was to assess structure‐activity relationships regarding the selectivity and potency of these compounds. Niflumic acid (1–100 μM) concentration‐dependently inhibited 5‐HT‐induced tonic contractions with an IC50 value (concentration reducing the control contractile response by 50%, calculated from semilog graphs) of 0.24 × 10−4 M (n = 9). In contrast, it was significantly less potent at inhibiting KCl‐induced responses (IC50 = 1.49 × 10−4 M, n = 9). The methyl ester (NFAme) and amido (NFAm) analogues showed no selectivity between 5‐HT‐ and KCl‐induced contractions with IC50 values of 1.64 × 10−4 M (n = 8) and 1.87 × 10−4 M (n = 9) for 5‐HT responses, and 2.61 × 10−4 M (n = 8) and 2.55 × 10−4 M (n = 7) for KCl‐induced responses, respectively. Our results suggest that alteration of the carboxylic acid moiety of niflumic acid reduces the selectivity and potency of its inhibitory action on 5‐HT‐induced contractile responses of the rat fundus, possibly via a reduced interaction with calcium‐activated chloride channels.