nrcms

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid. 17R(18S)-EpETE activates large-conductance calcium-activated potassium (BKCa) channels, increasing potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells at +60 mV at 50 nM. 17R(18S)-EpETE also exerts negative chronotropic effects in neonatal rat cardiomyocytes with an EC50 of ~1–2 nM and prevents calcium-induced increases in spontaneous beating. 17R(18S)-EpETE is therefore used in cardiovascular electrophysiology research systems to investigate ion channel modulation, lipid mediator signaling, and cardiac excitability regulation in cellular models.

19R(20S)-EpDPA is an oxylipin and a metabolite of docosahexaenoic acid .1,2It is formed from DHA by various cytochrome P450 (CYP) isoforms in a stereoselective manner.219R(20S)-EpDPA (30 nM) prevents calcium-induced increases in the spontaneous beating of isolated neonatal rat cardiomyocytes (NRCMs).3 1.Cinelli, M.A., Yang, J., Scharmen, A., et al.Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acidsJ. Lipid Res.59(11)2237-2252(2018) 2.Lucas, D., Goulitquer, S., Marienhagen, J., et al.Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450J. Lipid Res.51(5)1125-1133(2010) 3.Burke, J.E., and Dennis, E.A.Phospholipase A2 structure/function, mechanism, and signalingJ. Lipid Res.50(Suppl)S237-S242(2009)