Biomedical Engineering Reference
In-Depth Information
therapeutic index. Chronic pain associated with cancer disease could be effec-
tive by treating it intrathecally with this peptide [
48
,
49
].
6. ZC-88: A novel nonpeptide NCC blocker is found to be very useful for the
treatment of acute and neuropathic pain. Recently, Meng et al. have synthesized
compound ZC88, which inhibited Ca
2+
currents mediated by NCC with high
potency and high selectivity. It blocked recombinant human NCC transiently
expressed in HEK-293 cells with 0.45
MofIC
50
value [
50
]. This
compound had notable oral analgesia and antiallodynia for acute and neuro-
pathic pain. It can be used alone or in combination with opioids because it
enhanced morphine analgesia while preventing morphine-induced tolerance and
physical dependence.
0.09
m
Pharmaceutical companies have patented many NCC blockers for the treatment
of neuropathic pain and cerebral ischemia. Some of these NCC patent reports are
depicted in Table
2
[
1
,
50
]. Antihypertensive drug cilnidipine was reported by
Takahara et al. group which is a 1,4-dihydropyridine derived long acting dual CCB,
which inhibits both LCC and NCC [
51
]. Yamamoto et al. group has recently
discovered novel series of 1,4-dihydro-pyridines and cyproheptadines as potent
Table 2 Some patent reports on selective N-type Ca
2+
channel blockers
Compound
NCC activity Patent no./year
Experimental assay/technique
0.048
m
M
Pfizer 2
WO 07125398/2007
Neuromed
1(NMED-160,
MK-6721)
WO 01045709/2001
WO 06105670/2006
0.04
m
M
Neuromed 2
0.17
m
M
WO 04089377/2004
Neuromed 3
0.14
m
M
WO 07071035/2007
Neuromed 4
0.09
m
M
WO 0804318/2008
Neuromed 5
0.06
m
M
WO 04089922/2004
Neuromed 6
0.38
m
M
WO 04105750/2004
In vitro assay using HEK293
cells transfected with
NCC. A patch clamp
technique was used
Neuromed 7
0.32
m
M
WO 08031227/2008
Neuromed 8
-
US 7507760/2009
Formula I
20
m
M
WO/2010/014257
>
Merck 1
Not available WO 07084394/2007
Merck 2
Not available WO 08066803/2008
Merck 3
Not available WO 07075524/2007
Merck 4
Not available WO 08133867/2008
Not available
Euro-Celtique 1
0.13
m
M
WO07110449/2007
Euro-Celtique 2
0.39
m
M
WO06040181/2006
Euro-Celtique 3
0.10
m
M
WO07118853/2007
Euro-Celtique- Shionogi 1 0.19
m
M
WO07118854/2007
Euro-Celtique- Shionogi 2 0.080
m
M
WO08008398/2008
Euro-Celtique- Shionogi 3 0.210
m
M
WO08150447/2008
Purdue 1
0.46
m
M
WO08124118/2008
Euro-Celtique 4
0.34
m
M
WO07085357/2007
In vitro assay using IMR32
human neuroblastoma cells
Euro-Celtique 5
0.23
m
M
WO07028638/2007
