C2230 is a potent, specific CaV2.2 (N-type) calcium channel inhibitor/antagonist with IC50 of 1.3 uM (depolarizing Vh of -50 mV), preferably binds to the inactivated CaV2.2 channels.
C2230 block of CaV2.2 is greater at -50 mV when compared to -80 mV (IC50=10.2 uM).
C2230 (20 µM) exhibits a fast onset and stable inhibition of CaV2.2 currents, with apparent inhibitory and recovery time constants values of 12.3 ± 1.7 sec and 9.9 ± 1.3 sec, respectively.
C2230 does not inhibit KV1.3, KV1.5, KV3.1, KV3.2, KV3.4, KV4.1, NaV1.3, NaV1.4, and NaV1.7-1.9 channels, and weak activity against both L-type (CaV1.2-1.3) and T-type (CaV3.1-3.3) calcium channels, KV2.1 and NaV1.5 channels (all IC50s >20 uM).
C2230 enhances the closed-state inactivation, accelerates the open-state inactivation and inhibits CaV2.2 channels during high-frequency stimulation.
C2230 inhibits CaV2.2 currents without affecting neuronal excitability in rat DRG neurons.
C2230 reduces evoked excitatory postsynaptic currents and excitatory neurotransmitter release in the spinal cord, leading to relief of neuropathic, orofacial, and osteoarthritic pain-like behaviors.
C2230 binds differently than other known CaV2.2 blockers.