Blue Biotechnology : Ziconotide as Painkiller

Biotechnology is a broad area of biology, involve the use of living system an

organism to develop or make products. The concept of biotechnolgy itself encompasses
a wide range of procedures for modifying living organism according to human
purposes, back to domestication of animals, cultivation of the plants, and improvements
to these through breeding programs that employ artificial selection and hybridization.
Modern usage also includes genetic engineering as well as cell and tissue culture
technologies. Biotechnology is the research and development in the laboratory using
bioinformatics for exploration, extraction, exploitation, and production from any living
organisms and any source of biomass by means of biochemical engineering where high
value-added products could be planned (reproduced by biosynthesis, for example),
forecasted, formulated, developed, manufatured, and marketed for the purpose of
sustainable operations.

Blue biotechnology is biotechnology using aquatic organisms, think the word “blue”
for the water that these organisms live in. we already utilize many aquatic resources
such as fish, shellfish, sponges, and petroleum reserves. Blue biotechnology goes
beyond those things, utilizing an incredible variety of organisms from oceans, lakes,
rivers, and streams for many different purposes. Blue biotechnology sectors look at
groups of marine organisms that until now often have been ignored for commercial
exploitation. This includes microorganism, algae, and invertebrates. Blue biotechnology
is the application of science and technology to living aquatic organism for the
production of knowledge, goods, and services (OECD, 2016).

Ziconotide is one of the results from biotechnology that already being used for
painkiller, it has more power than morphine and also only acts in specific regions of the
spinal record. Ziconotide is made from the toxin of the cone snail species, Conus
Magus. Scientist has been intrigued by the effects of the thousands of chemicals in
marine snail toxins since the initial investigations in the late 1960’s. Ziconotide (SNX-
111; Prialt), or also called intrathecal ziconotide (ITZ) because of its administration
route, is an atypical analgesic agent for the amelioration of severe and chronic pain.
Ziconotide is a peptide with the amino acid sequence H-Cys-Lys-Gly-Lys-Gly-Ala-Lys-
Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-Lys-Cys-NH2 (
CKGKGAKCSRLMYDCCTGSCRSGKC-NH2) and contains 3 disulfide bonds (Cys1-
Cys16, Cys8-Cys20, and Cys15-Cys25). Ziconotide was developed into an artificially
manufactured drug by Elan Corporation. It was approved for sale under the name Prialt
by the U. S. Food and Drug Administration on December 28, 2004. Azur Pharma
acquired worldwide rights (except Europe) to Prialt in 2010.

Ziconotide is a hydrophilic molecule that is freely soluble in water and is practically

insoluble in methyl t-butl ether. Ziconotide acts as a selective N-type voltage-gated
calcium channel blocker (Miljanich, 2004). This action inhibits the release of pro-
nociceptive neurochemicals like glutamate, calcitonin gene-related peptide (CGRP), and
substance P in the brain and spinal cord, resulting in pain relief (McGivern, 2007). Due
to the profound side effects or lack of efficacy when delivered through more common
routes, such as orally or intravenously, ziconotide must be administred intrathecally (i.e
directly into the spinal fluid). As this is the most expensive and invasive method of drug
and involves additional risks of its own (Daniel P, 2005).

Ziconotide therapy is generally considered appropriate (as evidenced by the range of

use approved by the FDA in the US) only for “management of severe chronic pain in
patients for whom intrathecal (IT) therapy is warranted and who are intolerant of or
refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT
morphine (Palca, 2015). Research is ongoing to determine whether ziconotide can be
formulated in a way that would allow it to be administered by less invasive means.
However, this must be weighed against the high level of pain management, both in
terms of degree and length, and the apparent lack of tolerance (Prommer, 2006) and
other signs of dependence (Klotz, 2006) even after extended treatment along with the
need for alternatives to other therapies that have not worked with certain preexisting
mental disorders (e. g. psychosis) due to evidence that they are more susceptible to
certain severe side effects.

The most common side effects are dizziness, nausea, confusion, nystagmus, and
headache. Others may include weakness, hypertonia, ataxia, abnormal vision, anorexia,
somnolence, unsteadiness on feet, vertigo, urinary retention, pruritus, increased
sweating, diarrhea, nausea, vomiting, asthenia, fever, rigors, sinusitis, muscle spasms,
myalgia, insomnia, anxiety, amnesia, nystagmus, tremor, memory impairment, and
induced psychiatric disorders. Other side effects which are less frequent but still
clinically significant include auditory and visual hallucinations, thoughts of suicide,
acute kidney failure, atrial fibrillation, cardiovascular accident, sepsis, new or
worsening depression, paranoia, disorientation, meningitis and seizures. Therefore, it is
contraindicated in people with a history of psychosis, schizophrenia, clinical depression,
and bipolar disorder. Recent incidents suggesting a link between intrathecal ziconotide
treatment and increased risk of suicide have led to calls for strict and ongoing
psychiatric monitoring of patients to avoid suicide occurring in vulnerable individuals
(Maier, 2010). There is no known antidote.
 References

Maier C, Gockel HH, Gruhn K, Krumova EK, Edel MA (October 2010). "Increased risk of
suicide under intrathecal ziconotide treatment? – A warning". Pain. 152 (1): 235–237.
doi:10.1016/j.pain.2010.10.007. PMID 21041028. S2CID 33370759.
McGivern JG (2007). "Ziconotide: a review of its pharmacology and use in the treatment of
pain". Neuropsychiatr Dis Treat. 3 (1): 69–85. doi:10.2147/nedt.2007.3.1.69. PMC
2654521. PMID 19300539.
Miljanich GP (2004). "Ziconotide: neuronal calcium channel blocker for treating severe
chronic pain". Curr Med Chem. 11 (23): 3029–40. doi:10.2174/0929867043363884.
PMID 15578997.
Klotz U (2006). "Ziconotide—a novel neuron-specific calcium channel blocker for the
intrathecal treatment of severe chronic pain—a short review". Int J Clin Pharmacol
Ther. 44 (10): 478–83. doi:10.5414/cpp44478. PMID 17063978.
Palca J (August 3, 2015). "Snail Venom Yields Potent Painkiller, But Delivering The Drug Is
Tricky". NPR. Retrieved August 5, 2015.
Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today. 42 (6):
369–78. doi:10.1358/dot.2006.42.6.973534. PMID 16845440.
Roberts, J. (ed.) (2016), Blue Biotechnology, Commonwealth Blue Economy Series, No. 5,
Commonwealth Secretariat, London, https://doi.org/10.14217/9781848599468-en.