Bupivacaine hydrochloride monohydrate is a potent NMDA receptor inhibitor of sodium, L-calcium, and potassium channels.Bupivacaine hydrochloride monohydrate inhibits SCN5A channels and is commonly used in the study of chronic pain.
In vitro, Bupivacaine hydrochloride monohydrate inhibits synaptic transmission mediated by NMDA receptors in the spinal dorsal horn, which is an area closely associated with central sensitization[1]. Bupivacaine hydrochloride monohydrate affects the voltage dependence of channel activation and steady-state inactivation by shifting the half-maximal activation/inactivation membrane potential to a slightly more negative membrane potential.In the inactivated state, the SCN5A channel shows slight sensitivity to Bupivacaine hydrochloride monohydrate (IC50=2.18±0.16 μM)[3]. Bupivacaine hydrochloride monohydrate reversibly inhibits SK2 channels in a dose-dependent manner, with an IC50 of 16.5 μM[2].
References:
[1]. Meaghan A Paganelli, et al. Actions of Bupivacaine, a widely used local anesthetic, on NMDA receptor responses. J Neurosci. 2015 Jan 14;35(2):831-42.
[2]. Carsten Stoetzer, et al. Inhibition of Voltage-Gated Na+ Channels by Bupivacaine Is Enhanced by the Adjuvants Buprenorphine, Ketamine, and Clonidine. Reg Anesth Pain Med.Jul/Aug 2017;42(4):462-468.
[3]. Alexander P Schwoerer, et al. A Comparative Analysis of Bupivacaine and Ropivacaine Effects on Human Cardiac SCN5A Channels. Anesth Analg. 2015 Jun;120(6):1226-34.