Background:

ZD 7288 is an inhibitor of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel [1].

The HCN channel is found in the sinoatrial node (SAN) and is permeable to both Na+ and K+. The HCN current exists in neurons under hyperpolarization of the cell membrane and plays an important role in neuropathic pain [1].

In CA1 pyramidal cells from Wistar rats, ZD 7288 inhibited T-type Ca2+ channel currents in a concentration-dependant way [2]. In neonatal rat facial motoneurones, ZD-7288 (0.1-10 μM) inhibited the hyperpolarisation-activated current with IC50 value of 0.2 μM in a time- and voltage-dependent way [3]. In CA1 pyramidal neurons, ZD 7288 (1-1000 μM) inhibited the hyperpolarization-activated current. However, ZD 7288 had no influence on long-term depression (LTD) of the CA3-CA1 synapse [4].

In rats with chronic visceral pain, ZD 7288 (50-100 nM) significantly inhibited abdominal withdrawal reflex (AWR) scores and electromyographic (EMG) responses. Also, ZD 7288 significantly increased pain thresholds. These results suggested that spinal HCN channels might play a critical role in chronic visceral pain [1].

参考文献:
[1].? Chen Y, Lin C, Tang Y, et al. ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats. World J Gastroenterol, 2014, 20(8): 2091-2097.
[2].? Sánchez-Alonso JL, Halliwell JV, Colino A. ZD 7288 inhibits T-type calcium current in rat hippocampal pyramidal cells. Neurosci Lett, 2008, 439(3): 275-280.
[3].? Larkman PM, Kelly JS. Modulation of the hyperpolarisation-activated current, Ih, in rat facial motoneurones in vitro by ZD-7288. Neuropharmacology, 2001, 40(8): 1058-1072.
[4].? Gasparini S, DiFrancesco D. Action of the hyperpolarization-activated current (Ih) blocker ZD 7288 in hippocampal CA1 neurons. Pflugers Arch, 1997, 435(1): 99-106.