Mental Disorders are very much common in nowadays.

Due to social & cultural issue the number of

patients suffering from psychotic disorder is increasing day by day. Though in Bangladesh they are not
been practiced too much, in USA, Britain or in Germany people are very much concerned to prevent
against psychosis.
There is not a correct statistics about psychotic disorder in Bangladesh. But if we look upon the statistics
of these disorders in a developed country like USA, we may assume that it may also become a thread to
our society. In United States of America There are about 26.2% people or one in four adults suffers from
psychotic disorder every year. This figure translated about 57.7 million people suffer from psychotic
disorder.

Percantage of People Suffering From Phychotic

Disorder in USA
Percantage of People Suffering From Phychotic Disorder
6.80%

6.70%
5.20%

5.20%

1.50%

3.50% 3.10%

2.70%

2.60%
1.10%

4.10%

1%

0.80% 0.60%

1%

Aside USA if we consider the United Kingdom, there are 8, 00,000 people are suffering from Alzheimer
where 17,000 younger people are suffering from dementia. 60,000 deaths a year are directly
attributable to dementia. Delaying the onset of dementia by 5 years would reduce deaths directly
attributable to dementia by 30,000 a year.

I got an interest regarding

this matter is due to being a
movie & book fan. I have got
to know that there are many
celebrities who are suffering
from various kinds of
psychotic disorder.
I was imagining if Gabriel
Garca Mrquez didnt suffer
from Alzheimers we may get
some more creative writing
like Chronicle of a death
foretold or love in the time of
cholera. We may enjoy some
super
punches
from
Muhammad Ali who is
suffering from Parkinsonism.
Besides we may get some
revolutionary music from the
guitar of Syd Barett if he hadnt suffered from schizophrenia. So antipsychotic drugs are now needed to
be discovered in order to call for a war against these diseases which interrupt the creativity.
I have visited several website but from them only 5 official website which are served by some famous
pharmaceutical Company are working on some drugs that act on central nervous system on the purpose
of treating against some psychosis & others. All of them have crossed the phase 3. Except one drug
named Arbaclofen which has been recently terminated due to fail in the phase-3.

Name of the Drug

Mechanism of action

Gantenerumab

Gantenerumab
neutralizes diseaserelevant aggregated
forms of amyloid-beta:
those that accumulate
as plaques in the brain
and those which
interfere with brain-cell
functioning.

Solanezumab

Solanezumab
neutralizes diseaserelevant aggregated
forms of amyloid-beta:
those that accumulate
as plaques in the brain
and those which
interfere with brain-cell

Purpose of
Use
Alzheimers
disease

Alzheimers
disease

Company
Roche
GroupPartner:Morphosys

Phase
III

III

Eli Lilly & Company

functioning.

Arbaclofen

Naloxegol

Bitopertin

Bitopertin

Istradefylline

Through the GABA-B

receptor, Arbaclofen is
being tested for its
effect on balance at the
synapse associated with
this disorder. But they
have terminated this
drug because of
unsuccessful results
in phase III clinical
trials.
.

Fragile X
Syndrome

F. Hoffmann-La Roche Ltd

III

a Mu() opioid receptor

antagonist for the
treatment of opioidinduced constipation
Glycine reuptake
inhibitor (GRI). Enhance
N-methyl-D-aspartate
(NMDA) receptor
activity.

Opioidinduced
constipation
(OIC)
Schizophrenia

Nektar

III

F. Hoffmann-La Roche Ltd

III

Glycine reuptake
inhibitor (GRI). Enhance
N-methyl-D-aspartate
(NMDA) receptor
activity.
Adenosine A2A
Receptor Antagonist

Schizophrenia

Parkinsonism

III

Kyowa Hakko Kirin Co. Ltd.

Table: Name of the drugs along with their action.

III

Alzheimers Disease
Alzheimers disease is characterized by progressive
impairment of memory and cognitive functions and may
lead to a completely vegetative state, resulting in
massive socioeconomic disruption, and early death.
There are two drugs have been developed from two
different company to act against Alzheimers disease
though their mechanism of action is same.
1.

2.

: Gantenerumab
:Roche
Morphosys
: Solanezumab
: Eli Lilly & Company
Some processes involved in Alzheimers disease. One of them is mitochondrial

dysfunction, possibly involving glucose utilization; synthesis of protein tau and aggregation in filamentous tangles;
synthesis of amyloid and secretion into the extracellular space, where it may interfere with synaptic signaling and
accumulates in plaques in the brain & interfere with brain-cell functioning. Gantenerumab neutralizes diseaserelevant aggregated forms of amyloid-beta: those that accumulate as plaques in the brain and those which
interfere with brain-cell functioning.

Gantenerumab & Solanezumab neutralizes disease-relevant aggregated forms of amyloid-beta()

those that accumulate as plaques in the brain and those which
interfere with brain-cell functioning.

Schizophrenia is a particular type of psychosis (that is, a

mental disorder caused by some inherent dysfunction of the
brain). It is characterized by delusions, hallucinations (often in
the form of voices), and thinking or speech disturbances.

Drugs: Bitopertin
These Drugs has been developed by two companies. They are:
1.Hoffmann-La Roche Ltd
2.

Mechanism of Action: Glycine is a required co-agonist along with glutamate for NMDA
receptors. That in turn activates our learning, thinking & memory skill. It has been
suggested that in patients with schizophrenia, the glycine site of the NMDA receptor is not
fully saturated. Bitopertin is an oral, small molecule glycine reuptake inhibitor (GRI).
Bitopertin is designed to enhance N-methyl-D-aspartate (NMDA) receptor activity.

Parkinsons Disease

It is a progressive
neurological disorder of
muscle movement,
characterized by tremors,
muscular rigidity,
bradykinesia(partial or complete loss of
muscle movement)

Drugs : Istradefylline (analogue of caffeine)

Company: kyowa Hakko Kirin Co. Ltd.
Mechanism of Action: Adenosine A2A Receptor
Antagonist
Adenosine: Adenosine has an inhibitory effect in the central nervous system (CNS). The
A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity. Then
it activates cAMP. As a result protein phosphorylation will be occurred that results the
influx of Calcium ion. It generally undergo sedation and catalepsy, reduces the normal
mobility resulting from activation of the dopaminergic receptors, and lowers the affinity
of agonists for the dopaminergic D2 receptors(involved in motor control function &
emotion). Istradefylline inhibits that adenosine A2A Receptor.

Fragile X syndrome: it is a genetic syndrome that is the most widespread single-gene cause
of autism and inherited cause of intellectual disability especially among boys. It results in a
spectrum of intellectual disabilities ranging from mild to severe as well as physical
characteristics such as an elongated face, large or protruding ears, and large testes
(macroorchidism), and behavioral characteristics such as stereotypic movements (e.g. handflapping), and social anxiety.
Name of the Drug: Arbaclofen
Company: F. Hoffmann-La Roche Ltd
Mechanism of Action:
Through the GABA-B receptor, Arbaclofen is being tested for its effect on balance at the
synapse associated with this disorder. But they have terminated this drug because of
unsuccessful results in phase III clinical trials.
According to the statement of Roche, While Roche is not continuing its support for Seasides
development of arbaclofen, it is important to note that Roche is currently one of only a few
companies committed to finding innovative treatment options for individuals with
neurodevelopmental conditions such as autism, fragile X and Down syndrome. Indeed, we

continue to investigate three compounds in clinical trials,

V1A (RG7314) for autism, mGluR5 (RG7090) for fragile X
and GABA-A a5 (RG1662) for Down syndrome.

Opioid Antagonist:
Name of the drug: Naloxegol
Company: Nektar
Mechanism of Action: Opioids are commonly prescribed
to patients experiencing chronic pain, which can provide
relief from serious medical conditions including
osteoarthritis, cancer, and chronic back pain. There are
about 250 million opioid prescriptions written annually in
the US alone to treat these conditions. Patients taking
opioids to treat chronic pain commonly experience a side
effect known as opioid-induced constipation, which may
include infrequent bowel movements and difficulty passing
stools or emptying bowels. Clinically, OIC is the most
prevalent side effect of opioid therapy. For those patients
who take opiates for long term pain management,
approximately 40-50 percent commonly experience
OIC.5 Only about 40-50 percent of those patients
experience effective relief from current treatment options.
Naloxegol (NKTR-118) is an investigational drug
candidate in Phase 3 studies being developed as a Mu()
opioid receptor antagonist for the treatment of opioidinduced constipation.
Combined oral naloxegol (NKTR-118) with selected
opioids, with the goal of treating pain without the side
effect of constipation traditionally associated with opioid
therapy.

Though in USA,UK,Germany are very much concerned about these disorders, in Bangladesh
tnot only the people but also the health professionals are not taking these disorders very
seriously. Especially the current political situation, depressing environment, urban culture &
globalized technology easily put the teen age under great frustration which further results
Bipolar disorder to schizophrenia. But in our culture if a puerile have a memory loss people just
thinks the person gets old nothing serious. If a teen age boy or girl has a hallucination it is called that
he/she is possessed by some supernatural power. It is a high time we need some proper step & some
counseling center rather than giving diazepam or levodopa without proper diagnosis.
Reference:

1. Lippincott's Illustrated Reviews: Pharmacology, 4th Edition

2. Ba s ic a nd Clin ica l P ha r m a cology, 12th Edition,Lange,Bertram
G. Katzung,Anthony J. Trevor,Susan B. Masters.
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583202/#!po=26.4706
4. http://schizophreniabulletin.oxfordjournals.org/content/38/5/92
0.abstract.html
5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181613/
6. Pharmacology of Adenosine A2a Receptors and Therapeutic
Applications
Bertil B. Fredholm,#* Rodrigo A. Cunha& and Per Svenningsson
7. http://www.ncbi.nlm.nih.gov/pubmed/10531461
8. http://www.nimh.nih.gov/statistics/index.shtml
9. http://www.nimh.nih.gov/health/publications/the-numbers-countmental-disorders-in-america/index.shtml
10. http://www.pdf.org/en/parkinson_statistics
11. http://www.alzheimers.org.uk/statistics