TTA-P2

TTA-P2 (T-Type calcium channel inhibitor) is a selective, orally active, and BBB-penetrant T-type calcium channel blocker (IC₅₀ = 22 nM). TTA-P2 reduces mechanical hypersensitivity and alleviates acute as well as chronic pain. TTA-P2 significantly reduces firing rates in temporal lobe epilepsy (TLE) neurons to control levels and suppresses synaptically evoked burst firing. TTA-P2 can be studied in research for neurological diseases such as tremor and absence epilepsy^[1][2][3]< sup>[4]^[5]. In Vitro:TTA-P2 (1-10 μM) inhibits most of the T current recorded at the holding potentials of -90 mV, and the inhibitory effect has a fast onset but was slowly and partially reversible in dorsal root ganglion (DRG) cells^[2].
TTA-P2 (3 μM, 10 min) has maximal effect within 3-4 min after application^[3].
TTA-P2 (1 μM, 70 min) fully recovers the window component of the T-type Ca²⁺ current (I_T) after 50 min of wash out in ventrobasal nucleus (VB) thalamocortical (TC) neurons^[3].
TTA-P2 (1 nM-1 μM) blocks I_T dose-dependently with an IC₅₀ of 22 nM in VB TC neurons ^[3].
TTA-P2 (1 μM, 20 min) induces a maximal reduction of I_T even in the absence of channel activation, indicating the absence of a use-dependent block in VB TC neurons ^[3].
TTA-P2 (25 nM, 20 min) induces a clear decrease in current amplitude with no apparent shift in the voltage dependence of channel activation and steady-state inactivation in VB TC neurons ^[3].
TTA-P2 (1 μM) decreases the amplitude of I_T recorded in rat nucleus reticularis thalami (NRT) neurons, whereas the high-voltage-activated (HVA) Ca²⁺ current in the same neurons is not affected^[3]. In Vivo:TTA-P2 (0.3-10 mg/kg, i.p., single dose) has no effects on the mechanical threshold at 0.3 mg/kg, while increases the mechanical threshold to 17 g at 1 mg/kg, to 19 g at 3 mg/kg, and to 26 g at 10 mg/kg in rat models using Von Frey testing starting at 4 g^[1].
TTA-P2 (5-7.5 mg/kg, i.p., single dose) significantly reduces licking and biting of the affected paws injected with formalin at 7.5 mg/kg in Ca_V3.2 knockout mice^[2].
TTA-P2 (5-10 mg/kg, i.p., single dose) allows complete reversal of neuropathic hyperalgesia at 10 mg/kg in diabetic Streptozocin (HY-13753)-treated rats^[2].
TTA-P2 (1-10 mg/kg, p.o., single dose) exhibits a dose- and exposure-dependent decrease in the total seizure time during the 4 h period following oral dosing, demonstrating robust CNS efficacy at 10 mg/kg with a plasma level of 1 μM in WAG/Rij rat model of absence epilepsy and significantly reduces tremor activity in a dose-dependent manner in rat harmaline model^[5].
TTA-P2 (1.29-4.30 (mg/kg)/60 min, i.v. infusion) has no significant impact in mean arterial blood pressure, heart rate or ECG intervals in dog models^[5].