T-type calcium channel blocker
CAS：357400-13-6
分子式：C30H40Cl2FN3O2
分子量：564.56
纯度：98%
存储：Store at -20°C

Background:

IC50: 6.8 μM for Cav3.1 T-type channel

NNC 55-0396 is a T-type calcium channel antagonist.

T-type calcium channel activity is reported to be a critical component of the spontaneous voltage oscillation of inferior olive neurons occurring at a frequency similar to that of essential tremor.

In vitro: NNC 55-0396 showed no effect against high voltage calcium channels at 100 μM, but inhibited T-type channels in HEK293 cells with a potency comparable to that of mibefradil (IC50 6.8 versus 10.1 μM) [1].

In vivo: NNC 55-0396 was better tolerated than mibefradil in the horizontalwire test. To assess for a potential interaction with harmaline in the inverted wire grid test, mice was given NNC 55-0396, followed by harmaline or vehicle. NNC 55-0396 ameliorated harmaline-induced test deficits. In the GABAA α1-null model, NNC 55-0396 at 12.5 mg/kg suppressed harmaline-induced tremor by half by 20–100 min, whereas mibefradil at the same dose did not significantly affect tremor. In contrast to mibefradil, NNC 55-0396 was well tolerated and suppresses tremor, and exerts less cytochrome P450 inhibition [1].

Clinical trial: N/A

Reference:
[1] Quesada A,Bui PH,Homanics GE,Hankinson O,Handforth A. Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor. Eur J Pharmacol.2011 May 20;659(1):30-6.