Biomedical Engineering Reference
In-Depth Information
Inflammation and injury of a nerve will directly lead to the upregulation of
the
a
1B
subunit. It was also well known that the toxins that block NCC affect the
peptidergic primary afferent neuronal function by reducing the release of the
glutamate and neuropeptides from its terminals [
37
]. The dorsal horn neuron
stimulus activity was also controlled by this process and it was mainly affected
with the injured nerve identified in the rat model system [
38
]. Recently, it was also
established that
a
1B
subunit gene knockout mice showed various abnormalities in
neurophysiological functions, such as locomotor activity, memory loss, and senso-
rimotor gating [
39
].
4 Review of Literature/Patent Survey on NCC Blockers
Selective NCC blockers could be used as therapeutic agent for the treatment of pain.
Blockade of NCCs has recently been shown for the treatment of the chronic pain
associated with cancer, AIDS, and neuropathy. Several drugs (or NCC blockers) are
in different stages of drug discovery program, and is depicted in Table
1
.
1. Ziconotide (also known as SNX111 or Prialt) an FDA approved drug is a potent
and selective NCC blocker and is a synthetic version of
-Conotoxin MVIIA
derived from marine snail
Conus magus
. It was administered intrathecally and
act as a novel nonopioid for the treatment of chronic pain [
40
]. This drug has
demonstrated efficacy in animal models of traumatic brain injury, focal cerebral
ischemia, and chronic pain [
41
,
42
]. However, to minimize the adverse effect of
this drug ,it was administered only via intrathecal route.
2. Morphine (also known as avinza, roxanol) is a potent narcotic pain reliever used
to treat moderate to severe pain. It is found in opium plant and is produced early
in its life cycle. It acts directly in the central nervous system for pain relief.
However, morphine has a high potential for physiological dependence, addic-
tion, and tolerance due to binding to opioid receptors. Adverse effects of this
drug include respiratory depression, renal failure, and constipation [
43
].
3. Gabapentin (also known as neurontin) drug was developed for the treatment of
epilepsy, but is now widely used to relieve neuropathic pain. This drug is a
useful alternative in the treatment of a number of different neuropathic pain
syndromes, including diabetic neuropathy, postherpetic neuralgia, trigeminal
neuralgia and migraine. In vitro study showed that it binds to the NCC
o
a
2
-
d
subunit for its down regulation [
44
,
45
].
4. NMED160: The lead compound developed by Neuromed company hopes for the
new generation of pain killers. NMED160 is in phase-II clinical trial, which
directly blocks the NCC by decreasing the Ca
2+
concentrations in the neuron and
releasing the neurotransmitters from synaptic vesicles [
46
,
47
].
5.
o
-Conotoxin CVID (also known as AM336) is a 27 amino acid peptide isolated
from the venom of Conus catus and is a selective NCC blocker with high
