CFM-2, a potent and selective non-competitive antagonist of AMPAR (AMPAR), exhibits anticonvulsant activity across various seizure models.

CFM-2 inhibits the extracellular signal-regulated kinase (ERK1/2) pathway, reduces phosphorylation of cAMP-responsive element-binding protein (CREB), and suppresses cyclin D1 expression. It upregulates cell cycle regulators and tumor suppressor proteins p21 and p53, consequently decreasing lung adenocarcinoma cell populations in the G2 and S phases of the cell cycle.

Pretreatment with CFM-2 delayed the progression of seizure rank during repeated administration of pentylenetetrazole. At the end of the period of repeated pentylenetetrazole treatment (6 weeks), the mean seizure score was 0 in vehicle-treated controls, 4.3 in animals treated with vehicle + pentylenetetrazole, 2.2 in rats treated chronically with CFM-2 (20 μmol/kg i.p.) + pentylenetetrazole and 1.0 in rats treated repeatedly with CFM-2 (50 μmol/kg i.p.) + pentylenetetrazole. CFM-2 was also able to antagonize the long-term increase in sensitivity of the convulsant effects of GABA function inhibitors in pentylenetetrazole-kindled animals [1]. CFM-2 has been proven to possess anticonvulsant activity in various models of seizures [2]. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 μg) and GYKI 52466 (50 μg), significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli [4].