assignment on medicinal chemistry(4th edition).pdf

7/26/2019 Assignment on Medicinal Chemistry(4th edition).pdf

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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 statisticsof 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.

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.

6.70%

1.50%

2.60%

5.20%

1.10%

2.70%

1%

3.50%3.10%

6.80%

0.80% 0.60%

4.10%

1%

5.20

Percantage of People Suffering From Phychotic

Disorder in USA

Percantage of People Suffering From Phychotic Disorder


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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 somerevolutionary 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 Purpose ofUse

Company Phase

Gantenerumab Gantenerumab

neutralizes disease-

relevant aggregated

forms of amyloid-beta:

those that accumulate

as plaques in the brain

and those which

interfere with brain-cell

functioning.

Alzheimers

disease

Roche

GroupPartner:Morphosys

III

Solanezumab Solanezumab

neutralizes disease-

relevant aggregated

forms of amyloid-beta:

those that accumulate

as plaques in the brain

and those which

interfere with brain-cell

Alzheimers

disease Eli Lilly & Company

III


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functioning.

Arbaclofen

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

inphase III clinicaltrials.

.

Fragile X

Syndrome

F. Hoffmann-La Roche Ltd III

Naloxegol a Mu() opioid receptor

antagonist for the

treatment of opioid-

induced constipation

Opioid-

induced

constipation

(OIC)

Nektar III

Bitopertin Glycine reuptake

inhibitor (GRI). Enhance

N-methyl-D-aspartate

(NMDA) receptor

activity.

Schizophrenia F. Hoffmann-La Roche Ltd III

Bitopertin Glycine reuptake

inhibitor (GRI). Enhance

N-methyl-D-aspartate

(NMDA) receptoractivity.

Schizophrenia III

Istradefylline

Adenosine A2A

Receptor Antagonist

Parkinsonism Kyowa Hakko Kirin Co. Ltd. III

Table: Name of the drugs along with their action.
http://en.wikipedia.org/wiki/Phases_of_clinical_research#Phase_IIIhttp://en.wikipedia.org/wiki/Phases_of_clinical_research#Phase_III


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Alzheimers Disease

Alzheimers disease is characterized by progressiveimpairment of memory and cognitive functions and maylead to a completely vegetative state, resulting inmassive socioeconomic disruption, and early death.

There are two drugs have been developed from twodifferent company to act against Alzheimers disease

though their mechanism of action is same.

1. : Gantenerumab

:Roche

Morphosys

2. : 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 disease-relevant 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.


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

mental disorder caused by some inherent dysfunction of thebrain). 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 beensuggested 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.


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( )


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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 ReceptorAntagonist

Adenosine: Adenosine has an inhibitory effect in the central nervous system (CNS). The

A2adenosine 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.


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Fragile X syndrome: it is a geneticsyndromethat is the most widespread single-gene cause

of autismand inherited cause of intellectual disabilityespecially 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. hand-

flapping), 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 thesynapse associated with this disorder. But they have terminated this drug because of

unsuccessful results inphase 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 fewcompanies committed to finding innovative treatment options for individuals withneurodevelopmental conditions such as autism, fragile X and Down syndrome. Indeed, we
http://en.wikipedia.org/wiki/Macroorchidismhttp://en.wikipedia.org/wiki/Macroorchidismhttp://en.wikipedia.org/wiki/Macroorchidismhttp://en.wikipedia.org/wiki/Phases_of_clinical_research#Phase_IIIhttp://en.wikipedia.org/wiki/Phases_of_clinical_research#Phase_IIIhttp://en.wikipedia.org/wiki/Macroorchidism


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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 prescribedto patients experiencing chronic pain, which can provide

relief from serious medical conditions includingosteoarthritis, cancer, and chronic back pain. There are

about 250 million opioid prescriptions written annually inthe US alone to treat these conditions. Patients taking

opioids to treat chronic pain commonly experience a sideeffect known as opioid-induced constipation, which may

include infrequent bowel movements and difficulty passingstools or emptying bowels. Clinically, OIC is the most

prevalent side effect of opioid therapy. For those patientswho take opiates for long term pain management,

approximately 40-50 percent commonly experienceOIC.

5Only 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 opioid-

induced 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.


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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 resultsBipolar 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 ageboy 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 sIllustrated Reviews: Pharmacology, 4th Edition

2. Basic and Clinical Pharmacology, 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/105314618. http://www.nimh.nih.gov/statistics/index.shtml

9. http://www.nimh.nih.gov/health/publications/the-numbers-count-

mental-disorders-in-america/index.shtml

10.http://www.pdf.org/en/parkinson_statistics

11.http://www.alzheimers.org.uk/statistics
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583202/#!po=26.4706http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583202/#!po=26.4706http://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181613/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181613/http://www.ncbi.nlm.nih.gov/pubmed/10531461http://www.ncbi.nlm.nih.gov/pubmed/10531461http://www.ncbi.nlm.nih.gov/pubmed/10531461http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181613/http://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://schizophreniabulletin.oxfordjournals.org/content/38/5/920.abstract.htmlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583202/#!po=26.4706


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