SlideShare a Scribd company logo
1 of 11
Download to read offline
Tanta University                          Senior Student
Faculty of Pharmacy                       Drug Design Course
Pharmaceutical Chemistry Department       2011/2012

  (Human Health Care Products introduced during 2011)
Student group number : 92

Generic / INN Name : Lurasidone

Brand Name : Latuda®

Chemical Structure :




Names of Student group in serial roll :
           Student name                      Serial roll
    1- Abdelrahman Wageeh Ahmed                 7631
    2- Abdelaziz Fahmy Abdelaziz                7632
    3- Abdelghany Hamed Abdelghany              7633
    4- Abdelfatah Magdy Abdelfatah              7634
    5- Abdullah Abdelnaby Hassan                7635
    6-Abdullah Essam Mohamed                    7636
    7-Abdullah Mohsen Ragheb                    7637

Under Supervision of :

                  Dr/ Eman El-Bastawisy
                  Dr/ Mervat El-Hamamsy
                  Ph/ Salma El-Sherbiny
1- Generic / INN Name : Lurasidone

2- Brand Name : Latuda®

3- Chemical Name :

      (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-
piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-
methanisoindol-1,3-dione .

4- CASR # : 367514-88-3

5- Innovative Company & ( Country ) :

          Dainippon Sumitomo Pharma Co., Ltd.
Which is a pharmaceutical company based in Japan. Its headquarters are
in Chuo-ku, Osaka.
          Current Manufacturer is Sunovion Pharmaceuticals.

6- Chemical Structure :
7- Production : chemical synthesis.




8- Type ( Break Through, Me Too, New Indication, Others ):
     Me too

9- Class ( ATC Coding System ) : N05AH
              N Nervous System
              N05 Psycholeptics
              N05A Antipsychotics
              N05AH Diazepines , Oxazepines , Thiazepines , Oxepines.

10- Indications :
       Lurasidone is the newest atypical antipsychotic (AA) agent
approved for the treatment of schizophrenia in adults. In clinical studies,
Lurasidone alleviates positive (e.g., hallucinations, delusions) without
inducing extra pyramidal side effects except for akathisia , despite its
potent D2 antagonistic actions. Clinical evidence of Lurasidone's effect on
negative symptoms of schizophrenia has yet to establish efficacy.
Lurasidone may be useful for treating cognitive and memory deficits seen
in schizophrenia for several reasons:
 1) unlike many other antipsychotics, Lurasidone does not block the
muscarinic acetylcholine receptors, an action well-known to impair
learning and memory
2) Lurasidone has prominent activity at 5-HT1A, 5-HT2A, 5-HT7, and α2C-
adrenergic receptors, all of which have been implicated in enhancement
of cognitive function if modulated properly. In animal studies,
Lurasidone was found to be superior to all of the other antipsychotics
examined in reversing dizocilpine-induced learning and memory
impairment, including risperidone, olanzapine, quetiapine, clozapine,
aripiprazole, and haloperidol.

11- Dosage Form(s) & Presentation(s) :
       Lurasidone is available in 40-mg and 80-mg tablets. The
recommended starting dose is 40 mg once daily, with a maximum dose of
80 mg/day. Higher doses provide no additional benefit and increase the
incidence of certain adverse reactions. The dosage should not exceed 40
mg/day in patients with moderate-to-severe renal or hepatic impairment
or in patients taking a moderate CYP3A4 inhibitor. Patients taking strong
CYP3A4 inhibitors or inducers should not take Lurasidone.




12- Chemical Mode of action at receptor site :
     Receptor Binding Profile :
Proposed mechanism of action of LATUDA




* The lower the Ki Value, The higher the affinity.
The mechanism of action of LATUDA, as with other drugs having
efficacy in schizophrenia, is unknown. It has been suggested that the
efficacy of LATUDA in schizophrenia is mediated through a combination
of central dopamine D2 and serotonin 5HT-2A receptor antagonism.

      In vitro receptor binding of LATUDA




The correlation between receptor binding affinities and clinical outcomes
is uncertain .

      Lurasidone is an isoindole derivative that has a unique receptor-
binding profile with high affinity for dopamine-2, serotonin- 2A,
serotonin-7, serotonin-1A, and noradrenaline-2C receptors. These
receptors are known to improve cognitive capabilities upon effective
regulation. The drug has limited affinity for histamine-1 and
acetylcholine- M1 receptors and is a partial agonist for the serotonin 5-
hydroxytryptamine (5HT)1A receptor. Lurasidone enhances the functions
of muscarinic acetylcholine receptors, which are known to aid in memory
and learning functions.
The dopamine D2-, D3-, D4 receptor

       There are two main
subgroups of dopamine receptor
– D1-like and D2-like. The D2-
like family contains the D2, D3
and D4 subtypes and the D1-like
receptor family contains the D1
and D5 receptor subtypes. The
D2-like receptors are found
throughout the brain and in
smooth muscle and presynaptic
nerve terminals. Coupled to
inhibitory G-proteins, dopamine
D2-like receptors have an
inhibitory effect on
neurotransmission when bound
by an agonist. Many neuroleptic
drugs are antagonists of the D2
receptors. This class of drug is used to treat psychotic disorders, such as
schizophrenia.


D2 receptor antagonist


       A D2 receptor
antagonist prevents
the activation of the
dopamine D2
receptor. The D2
receptor is coupled
to inhibitory G-
proteins, which
dissociate from the
receptor on agonist
binding and inhibit
secondary messenger signaling mechanisms. This causes inhibition of
down-stream signaling mechanisms. Antagonist binding inhibits this
usual process, resulting in cell depolarization.
Serotonin 5HT-2A receptor antagonism :
13- Pharmacophoric group :

        (1R,2S,6R,7S)-4-{[(1R,2R)-2-{[4-(1,2-Benzothiazol-3-yl)-1-
piperazinyl]methyl}cyclohexyl]methyl}-4-azatricyclo[5.2.1.02,6]decane-
3,5-dione , structure shows 6 stereocenters that have major influence on
its action as atypical antipsychotic drug .




14- Expected ADME Profile :

- Absorption
       Lurasidone is absorbed and reaches highest concentration in 1-3
hours. Nine to 19 percent of oral
administered dose is absorbed into the system. Its level is enhanced with
food consumption.
Cmax and AUC are increased by 3-times and 2-times, respectively, in the
presence of food.
- Distribution
       98.8% of Lurasidone molecules is bound to plasma protein .
- Metabolism
       Lurasidone is metabolized by CYP3A4 via oxidative N-
dealkylation, hydroxylation and S oxidation.
Major metabolites include two active and two non-active forms.
- Elimination
       80% is excreted in feces and 9% in urine.
15- Structures , Generic name(s) & Brand name(s) of related drugs :

Generic Name    Brand Name         Structure
Chloropromazine Largactil®
                (Sanofi Aventis) ,
                Thorazine®
                (GlaxoSmithKline


Haloperidol      Haldol®
                 (Janssen Pharm) ,
                 Serenace®
                 (Pfizer)
Quetiapine       Seroquel®
                 (Sun Pharma)




Clozapine        Clozaril®
                 (Novartis)




Olanzapine       Zyprexa®
                 (Eli Lilly)




Aripiprazole     Abilify ®
                 (Bristol Myers
                 Squibb)
16- SAR of drug relative to other available drugs for the same
indication :
       Lurasidone is a chiral benzoisothiazol derivative - the
benzoisothiazol is the fused five-six dual ring structure on the right of the
figure. Its structure contains an imide heterocyclic and a piperazine
functional group. The central piperazine nitrogen is basic. The chemical
structure, properties and pharmacology are similar to Ziprasidone.




17- Advantages & Disadvantages of Drugs relative to other available
drugs :
- Favorable efficacy and safety profile than other antischizophrenic drugs.
- LATUDA is contraindicated with strong CYP3A4 inhibitors (e.g.,
ketoconazole) and strong CYP3A4 inducers (e.g., rifampin).
- Increased Mortality in elderly patients with Dementia – Related
Psychosis (a severe mental health problem) . An increased risk for stroke
and mini stroke has been reported in elderly people with dementia-related
psychosis.
- Neuroleptic malignant syndrome (NMS):
       High fever; stiff muscles; confusion; changes in pulse, heart rate,
or blood pressure; sweating; or muscle pain and weakness. Treatment
should be stopped if you have NMS.
- Tardive dyskinesia (TD): TD is a serious and sometimes permanent
side effect reported with LATUDA and similar medicines. TD includes
uncontrollable movements of the face, tongue, and other parts of the
body. The risk for developing TD and the chance that it will become
permanent is thought to increase the longer a person takes the medicine
and the more medicine a person takes over time. TD can develop after a
person has been taking the medicine for a short time at low doses,
although this is much less common. There is no known treatment for TD,
but it may go away partially or completely if the person stops taking the
medicine.
- Metabolic changes :
a) High blood sugar.
b) High cholesterol and triglycerides.
c) Weight gain.

18 Future Outlook :
       Latuda is predicted to be the number one selling atypical
antipsychotic drug in the upcoming new years . Latuda binding to
receptor may be enhanced to gain more efficiency and potency , may
some modification make more potent drug and modify the partial agonist
activity of the drug on the serotonin 5-hydroxytryptamine (5HT)1A
receptor . Additional research is running to help developing the drug as
third generation atypical antipsychotic drug.

19- References :

www.wikipedia.org
www.fda.gov
www.Latuda.com
www.latudahcp.com
www.medscape.com
www.chemspider.com
www.Drugbank.ca
www.chemdrug.com
www.dailymed.nlm.nih.gov
Journals :
NDA Application number (200603) Medical Reviews.
NDA Application number (200603) Chemical Reviews.
NDA Application number (200602) Proprietay Name Reviews.
Latuda Prescribing Information ( Available on www.Latudahcp.com )

More Related Content

What's hot

Hanipsych, novel antipsychotics
Hanipsych, novel antipsychoticsHanipsych, novel antipsychotics
Hanipsych, novel antipsychoticsHani Hamed
 
Drug therapy of depression
Drug therapy of depression Drug therapy of depression
Drug therapy of depression Dr Htet
 
Polypharmacy in Psychiatry
Polypharmacy in PsychiatryPolypharmacy in Psychiatry
Polypharmacy in Psychiatrydonthuraj
 
Pharmacological treatment of schizophrenia
Pharmacological treatment of schizophreniaPharmacological treatment of schizophrenia
Pharmacological treatment of schizophreniajoanna1956
 
Antidepressants Part I
Antidepressants Part IAntidepressants Part I
Antidepressants Part IBrian Piper
 
Pharmacotherapy of depression
Pharmacotherapy of depressionPharmacotherapy of depression
Pharmacotherapy of depressionDr.Ameya Puranik
 
Newer atypical antipsychotic agents
Newer atypical antipsychotic agentsNewer atypical antipsychotic agents
Newer atypical antipsychotic agentsYashasree Poudwal
 
Asenapine & agomelatine
Asenapine & agomelatineAsenapine & agomelatine
Asenapine & agomelatineJervinM
 
Drug profile of pregabalin and lacosamide: A deep insight!
Drug profile of pregabalin and lacosamide: A deep insight!Drug profile of pregabalin and lacosamide: A deep insight!
Drug profile of pregabalin and lacosamide: A deep insight!RxVichuZ
 
Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...
Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...
Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...iosrphr_editor
 
Prozac What You Should Know Before You Use
Prozac  What You Should Know Before You UseProzac  What You Should Know Before You Use
Prozac What You Should Know Before You UseDr Neelesh Bhandari
 
Sevikar Brochure.pptx
Sevikar Brochure.pptxSevikar Brochure.pptx
Sevikar Brochure.pptxdanapharmacy
 
Antipsychotics and updates
Antipsychotics and updatesAntipsychotics and updates
Antipsychotics and updatesJyoti Sharma
 
Depakote (valproic acid)
Depakote (valproic acid)Depakote (valproic acid)
Depakote (valproic acid)Baleigh Brown
 
Drug interactions in psychiatry
Drug interactions in psychiatryDrug interactions in psychiatry
Drug interactions in psychiatryDr.Pj Chakma
 
Amisulpride@ use in psychotic illnesses
Amisulpride@ use in psychotic illnessesAmisulpride@ use in psychotic illnesses
Amisulpride@ use in psychotic illnessesSujit Kumar Kar
 
Risperidone by Dr Sarang Pandit
Risperidone by Dr Sarang PanditRisperidone by Dr Sarang Pandit
Risperidone by Dr Sarang Panditsarangpan
 
Antipsychotics and mood stabilizers in pregnancy
Antipsychotics and mood stabilizers in pregnancyAntipsychotics and mood stabilizers in pregnancy
Antipsychotics and mood stabilizers in pregnancyMohamed Sedky
 

What's hot (20)

Hanipsych, novel antipsychotics
Hanipsych, novel antipsychoticsHanipsych, novel antipsychotics
Hanipsych, novel antipsychotics
 
Drug therapy of depression
Drug therapy of depression Drug therapy of depression
Drug therapy of depression
 
Polypharmacy in Psychiatry
Polypharmacy in PsychiatryPolypharmacy in Psychiatry
Polypharmacy in Psychiatry
 
Pharmacological treatment of schizophrenia
Pharmacological treatment of schizophreniaPharmacological treatment of schizophrenia
Pharmacological treatment of schizophrenia
 
Antidepressants Part I
Antidepressants Part IAntidepressants Part I
Antidepressants Part I
 
Pharmacotherapy of depression
Pharmacotherapy of depressionPharmacotherapy of depression
Pharmacotherapy of depression
 
Newer atypical antipsychotic agents
Newer atypical antipsychotic agentsNewer atypical antipsychotic agents
Newer atypical antipsychotic agents
 
Asenapine & agomelatine
Asenapine & agomelatineAsenapine & agomelatine
Asenapine & agomelatine
 
Drug profile of pregabalin and lacosamide: A deep insight!
Drug profile of pregabalin and lacosamide: A deep insight!Drug profile of pregabalin and lacosamide: A deep insight!
Drug profile of pregabalin and lacosamide: A deep insight!
 
Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...
Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...
Silodosin versus tamsulosin in symptomatic benign prostatic hyperplasia-Our e...
 
Prozac What You Should Know Before You Use
Prozac  What You Should Know Before You UseProzac  What You Should Know Before You Use
Prozac What You Should Know Before You Use
 
Sevikar Brochure.pptx
Sevikar Brochure.pptxSevikar Brochure.pptx
Sevikar Brochure.pptx
 
Antipsychotics and updates
Antipsychotics and updatesAntipsychotics and updates
Antipsychotics and updates
 
Depakote (valproic acid)
Depakote (valproic acid)Depakote (valproic acid)
Depakote (valproic acid)
 
Drug interactions in psychiatry
Drug interactions in psychiatryDrug interactions in psychiatry
Drug interactions in psychiatry
 
Invega
InvegaInvega
Invega
 
Levetiracetam
LevetiracetamLevetiracetam
Levetiracetam
 
Amisulpride@ use in psychotic illnesses
Amisulpride@ use in psychotic illnessesAmisulpride@ use in psychotic illnesses
Amisulpride@ use in psychotic illnesses
 
Risperidone by Dr Sarang Pandit
Risperidone by Dr Sarang PanditRisperidone by Dr Sarang Pandit
Risperidone by Dr Sarang Pandit
 
Antipsychotics and mood stabilizers in pregnancy
Antipsychotics and mood stabilizers in pregnancyAntipsychotics and mood stabilizers in pregnancy
Antipsychotics and mood stabilizers in pregnancy
 

Viewers also liked

Asenapine In Schizophrenia
Asenapine In SchizophreniaAsenapine In Schizophrenia
Asenapine In Schizophreniaperezcruzisabel
 
THE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICS
THE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICSTHE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICS
THE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICSSubrata Naskar
 
Sodium Valproate & Epilepsy: Dr Vijay Sardana
Sodium Valproate & Epilepsy: Dr Vijay SardanaSodium Valproate & Epilepsy: Dr Vijay Sardana
Sodium Valproate & Epilepsy: Dr Vijay SardanaVijay Sardana
 
Clinical profile of Valproate
Clinical profile of ValproateClinical profile of Valproate
Clinical profile of ValproateAhmed Elaghoury
 
Sodium valproate ppt
Sodium valproate pptSodium valproate ppt
Sodium valproate pptanu000712
 
Alternative Therapy Treatments for Depression and Anxiety
Alternative Therapy Treatments for Depression and AnxietyAlternative Therapy Treatments for Depression and Anxiety
Alternative Therapy Treatments for Depression and AnxietyMidtown TMS Treatment Center
 
Atypical antipsychotics
Atypical antipsychoticsAtypical antipsychotics
Atypical antipsychoticsKarrar Husain
 
Schizophrenia Past, Present and Future
Schizophrenia Past, Present and FutureSchizophrenia Past, Present and Future
Schizophrenia Past, Present and FutureAdonis Sfera, MD
 
Anti psychotic drugs
Anti psychotic drugsAnti psychotic drugs
Anti psychotic drugsDr Renju Ravi
 
The neuroanatomical explanation for schizophrenia
The neuroanatomical explanation for schizophreniaThe neuroanatomical explanation for schizophrenia
The neuroanatomical explanation for schizophreniaRobDan93
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychoticsraj kumar
 

Viewers also liked (20)

Slideshare ppt
Slideshare pptSlideshare ppt
Slideshare ppt
 
Asenapine In Schizophrenia
Asenapine In SchizophreniaAsenapine In Schizophrenia
Asenapine In Schizophrenia
 
Teens Suicide
Teens SuicideTeens Suicide
Teens Suicide
 
THE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICS
THE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICSTHE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICS
THE NEUROBIOLOGY OF PSYCHOSIS AND THE ROLE OF ANTIPSYCHOTICS
 
SODIUM VALPROATE
SODIUM VALPROATESODIUM VALPROATE
SODIUM VALPROATE
 
Sodium Valproate & Epilepsy: Dr Vijay Sardana
Sodium Valproate & Epilepsy: Dr Vijay SardanaSodium Valproate & Epilepsy: Dr Vijay Sardana
Sodium Valproate & Epilepsy: Dr Vijay Sardana
 
Classified Education Leaders - February 2017
Classified Education Leaders - February 2017Classified Education Leaders - February 2017
Classified Education Leaders - February 2017
 
Clinical profile of Valproate
Clinical profile of ValproateClinical profile of Valproate
Clinical profile of Valproate
 
Sodium valproate ppt
Sodium valproate pptSodium valproate ppt
Sodium valproate ppt
 
Alternative Therapy Treatments for Depression and Anxiety
Alternative Therapy Treatments for Depression and AnxietyAlternative Therapy Treatments for Depression and Anxiety
Alternative Therapy Treatments for Depression and Anxiety
 
Atypical antipsychotics
Atypical antipsychoticsAtypical antipsychotics
Atypical antipsychotics
 
Atypical antipsychotics
Atypical antipsychoticsAtypical antipsychotics
Atypical antipsychotics
 
Schizophrenia Past, Present and Future
Schizophrenia Past, Present and FutureSchizophrenia Past, Present and Future
Schizophrenia Past, Present and Future
 
Drug Profile: Aripiprazole
Drug Profile: AripiprazoleDrug Profile: Aripiprazole
Drug Profile: Aripiprazole
 
Anti psychotic drugs
Anti psychotic drugsAnti psychotic drugs
Anti psychotic drugs
 
The neuroanatomical explanation for schizophrenia
The neuroanatomical explanation for schizophreniaThe neuroanatomical explanation for schizophrenia
The neuroanatomical explanation for schizophrenia
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 
Antipsychotics - drdhriti
Antipsychotics - drdhritiAntipsychotics - drdhriti
Antipsychotics - drdhriti
 
Schizophrenia
SchizophreniaSchizophrenia
Schizophrenia
 
Schizophrenia
SchizophreniaSchizophrenia
Schizophrenia
 

Similar to Tanta University Senior Student Latuda Drug Design Course Report

ADHD in adult: advances in pharmacological interventions
ADHD in adult: advances in pharmacological interventionsADHD in adult: advances in pharmacological interventions
ADHD in adult: advances in pharmacological interventionsYasir Hameed
 
Bromocriptine 130412172318-phpapp02
Bromocriptine 130412172318-phpapp02Bromocriptine 130412172318-phpapp02
Bromocriptine 130412172318-phpapp02sandeepreddymaadhu
 
Advancement in anti-depression drugs
Advancement in anti-depression drugsAdvancement in anti-depression drugs
Advancement in anti-depression drugsDiwyanshi Zinzuvadia
 
Loratadine 10 mg tablets smpc taj pharmaceuticals
Loratadine 10 mg tablets smpc  taj pharmaceuticalsLoratadine 10 mg tablets smpc  taj pharmaceuticals
Loratadine 10 mg tablets smpc taj pharmaceuticalsTaj Pharma
 
Clinical Pharmacy - Drug Profile of Levodopa
Clinical Pharmacy - Drug Profile of LevodopaClinical Pharmacy - Drug Profile of Levodopa
Clinical Pharmacy - Drug Profile of LevodopaMohni Rasheed Chaudry
 
SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)
SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)
SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)RxVichuZ
 
antipsychotics.pptx
antipsychotics.pptxantipsychotics.pptx
antipsychotics.pptxMarxxYeager
 
Bromocriptine for Special Population - Adult ADHD
Bromocriptine for Special Population - Adult ADHDBromocriptine for Special Population - Adult ADHD
Bromocriptine for Special Population - Adult ADHDOlayinka Awofodu
 
SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!
SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!
SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!RxVichuZ
 
RECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptx
RECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptxRECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptx
RECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptxashharnomani
 
Schizophrenia and Psychosis: Antipsychotics
Schizophrenia and Psychosis: AntipsychoticsSchizophrenia and Psychosis: Antipsychotics
Schizophrenia and Psychosis: AntipsychoticsPranav Sopory
 
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptxRoberto Scarafia
 
Management of parkinsons disease
Management of parkinsons diseaseManagement of parkinsons disease
Management of parkinsons diseasesadaf89
 

Similar to Tanta University Senior Student Latuda Drug Design Course Report (20)

ADHD in adult: advances in pharmacological interventions
ADHD in adult: advances in pharmacological interventionsADHD in adult: advances in pharmacological interventions
ADHD in adult: advances in pharmacological interventions
 
Case study of schizophrenia
Case study of schizophreniaCase study of schizophrenia
Case study of schizophrenia
 
Presentation
PresentationPresentation
Presentation
 
Bromocriptine 130412172318-phpapp02
Bromocriptine 130412172318-phpapp02Bromocriptine 130412172318-phpapp02
Bromocriptine 130412172318-phpapp02
 
Advancement in anti-depression drugs
Advancement in anti-depression drugsAdvancement in anti-depression drugs
Advancement in anti-depression drugs
 
Loratadine 10 mg tablets smpc taj pharmaceuticals
Loratadine 10 mg tablets smpc  taj pharmaceuticalsLoratadine 10 mg tablets smpc  taj pharmaceuticals
Loratadine 10 mg tablets smpc taj pharmaceuticals
 
Antipsychotics update
Antipsychotics updateAntipsychotics update
Antipsychotics update
 
Clinical Pharmacy - Drug Profile of Levodopa
Clinical Pharmacy - Drug Profile of LevodopaClinical Pharmacy - Drug Profile of Levodopa
Clinical Pharmacy - Drug Profile of Levodopa
 
SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)
SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)
SSRIs(Antidepressants): A deep insight: By RxVichuZ!! ;)
 
antipsychotics.pptx
antipsychotics.pptxantipsychotics.pptx
antipsychotics.pptx
 
Parkinson disease
Parkinson diseaseParkinson disease
Parkinson disease
 
Class deaddiction 2
Class deaddiction 2Class deaddiction 2
Class deaddiction 2
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 
Bromocriptine for Special Population - Adult ADHD
Bromocriptine for Special Population - Adult ADHDBromocriptine for Special Population - Adult ADHD
Bromocriptine for Special Population - Adult ADHD
 
SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!
SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!
SCHIZOPHRENIA- A BRIEF INSIGHT....By Rxvichu!
 
RECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptx
RECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptxRECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptx
RECENT ADVANCES IN THE TREATMENT OF PARKINSON’S DISEASE.pptx
 
Schizophrenia and Psychosis: Antipsychotics
Schizophrenia and Psychosis: AntipsychoticsSchizophrenia and Psychosis: Antipsychotics
Schizophrenia and Psychosis: Antipsychotics
 
Amisulpride.pptx
Amisulpride.pptxAmisulpride.pptx
Amisulpride.pptx
 
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx
20180202 3 j. lombard genomind milan relazione part 2 to pub.pptx
 
Management of parkinsons disease
Management of parkinsons diseaseManagement of parkinsons disease
Management of parkinsons disease
 

Recently uploaded

Measures of Dispersion and Variability: Range, QD, AD and SD
Measures of Dispersion and Variability: Range, QD, AD and SDMeasures of Dispersion and Variability: Range, QD, AD and SD
Measures of Dispersion and Variability: Range, QD, AD and SDThiyagu K
 
Sanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdfSanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdfsanyamsingh5019
 
Unit-IV- Pharma. Marketing Channels.pptx
Unit-IV- Pharma. Marketing Channels.pptxUnit-IV- Pharma. Marketing Channels.pptx
Unit-IV- Pharma. Marketing Channels.pptxVishalSingh1417
 
IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...
IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...
IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...PsychoTech Services
 
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptxSOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptxiammrhaywood
 
Accessible design: Minimum effort, maximum impact
Accessible design: Minimum effort, maximum impactAccessible design: Minimum effort, maximum impact
Accessible design: Minimum effort, maximum impactdawncurless
 
Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...EduSkills OECD
 
Advanced Views - Calendar View in Odoo 17
Advanced Views - Calendar View in Odoo 17Advanced Views - Calendar View in Odoo 17
Advanced Views - Calendar View in Odoo 17Celine George
 
Measures of Central Tendency: Mean, Median and Mode
Measures of Central Tendency: Mean, Median and ModeMeasures of Central Tendency: Mean, Median and Mode
Measures of Central Tendency: Mean, Median and ModeThiyagu K
 
Introduction to Nonprofit Accounting: The Basics
Introduction to Nonprofit Accounting: The BasicsIntroduction to Nonprofit Accounting: The Basics
Introduction to Nonprofit Accounting: The BasicsTechSoup
 
Russian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in Delhi
Russian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in DelhiRussian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in Delhi
Russian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in Delhikauryashika82
 
Q4-W6-Restating Informational Text Grade 3
Q4-W6-Restating Informational Text Grade 3Q4-W6-Restating Informational Text Grade 3
Q4-W6-Restating Informational Text Grade 3JemimahLaneBuaron
 
Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...
Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...
Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...Krashi Coaching
 
1029-Danh muc Sach Giao Khoa khoi 6.pdf
1029-Danh muc Sach Giao Khoa khoi  6.pdf1029-Danh muc Sach Giao Khoa khoi  6.pdf
1029-Danh muc Sach Giao Khoa khoi 6.pdfQucHHunhnh
 
Sports & Fitness Value Added Course FY..
Sports & Fitness Value Added Course FY..Sports & Fitness Value Added Course FY..
Sports & Fitness Value Added Course FY..Disha Kariya
 
Disha NEET Physics Guide for classes 11 and 12.pdf
Disha NEET Physics Guide for classes 11 and 12.pdfDisha NEET Physics Guide for classes 11 and 12.pdf
Disha NEET Physics Guide for classes 11 and 12.pdfchloefrazer622
 

Recently uploaded (20)

Código Creativo y Arte de Software | Unidad 1
Código Creativo y Arte de Software | Unidad 1Código Creativo y Arte de Software | Unidad 1
Código Creativo y Arte de Software | Unidad 1
 
Mattingly "AI & Prompt Design: The Basics of Prompt Design"
Mattingly "AI & Prompt Design: The Basics of Prompt Design"Mattingly "AI & Prompt Design: The Basics of Prompt Design"
Mattingly "AI & Prompt Design: The Basics of Prompt Design"
 
Measures of Dispersion and Variability: Range, QD, AD and SD
Measures of Dispersion and Variability: Range, QD, AD and SDMeasures of Dispersion and Variability: Range, QD, AD and SD
Measures of Dispersion and Variability: Range, QD, AD and SD
 
Sanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdfSanyam Choudhary Chemistry practical.pdf
Sanyam Choudhary Chemistry practical.pdf
 
Unit-IV- Pharma. Marketing Channels.pptx
Unit-IV- Pharma. Marketing Channels.pptxUnit-IV- Pharma. Marketing Channels.pptx
Unit-IV- Pharma. Marketing Channels.pptx
 
IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...
IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...
IGNOU MSCCFT and PGDCFT Exam Question Pattern: MCFT003 Counselling and Family...
 
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptxSOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
SOCIAL AND HISTORICAL CONTEXT - LFTVD.pptx
 
Accessible design: Minimum effort, maximum impact
Accessible design: Minimum effort, maximum impactAccessible design: Minimum effort, maximum impact
Accessible design: Minimum effort, maximum impact
 
Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
 
Advanced Views - Calendar View in Odoo 17
Advanced Views - Calendar View in Odoo 17Advanced Views - Calendar View in Odoo 17
Advanced Views - Calendar View in Odoo 17
 
Measures of Central Tendency: Mean, Median and Mode
Measures of Central Tendency: Mean, Median and ModeMeasures of Central Tendency: Mean, Median and Mode
Measures of Central Tendency: Mean, Median and Mode
 
Advance Mobile Application Development class 07
Advance Mobile Application Development class 07Advance Mobile Application Development class 07
Advance Mobile Application Development class 07
 
Mattingly "AI & Prompt Design: Structured Data, Assistants, & RAG"
Mattingly "AI & Prompt Design: Structured Data, Assistants, & RAG"Mattingly "AI & Prompt Design: Structured Data, Assistants, & RAG"
Mattingly "AI & Prompt Design: Structured Data, Assistants, & RAG"
 
Introduction to Nonprofit Accounting: The Basics
Introduction to Nonprofit Accounting: The BasicsIntroduction to Nonprofit Accounting: The Basics
Introduction to Nonprofit Accounting: The Basics
 
Russian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in Delhi
Russian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in DelhiRussian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in Delhi
Russian Escort Service in Delhi 11k Hotel Foreigner Russian Call Girls in Delhi
 
Q4-W6-Restating Informational Text Grade 3
Q4-W6-Restating Informational Text Grade 3Q4-W6-Restating Informational Text Grade 3
Q4-W6-Restating Informational Text Grade 3
 
Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...
Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...
Kisan Call Centre - To harness potential of ICT in Agriculture by answer farm...
 
1029-Danh muc Sach Giao Khoa khoi 6.pdf
1029-Danh muc Sach Giao Khoa khoi  6.pdf1029-Danh muc Sach Giao Khoa khoi  6.pdf
1029-Danh muc Sach Giao Khoa khoi 6.pdf
 
Sports & Fitness Value Added Course FY..
Sports & Fitness Value Added Course FY..Sports & Fitness Value Added Course FY..
Sports & Fitness Value Added Course FY..
 
Disha NEET Physics Guide for classes 11 and 12.pdf
Disha NEET Physics Guide for classes 11 and 12.pdfDisha NEET Physics Guide for classes 11 and 12.pdf
Disha NEET Physics Guide for classes 11 and 12.pdf
 

Tanta University Senior Student Latuda Drug Design Course Report

  • 1. Tanta University Senior Student Faculty of Pharmacy Drug Design Course Pharmaceutical Chemistry Department 2011/2012 (Human Health Care Products introduced during 2011) Student group number : 92 Generic / INN Name : Lurasidone Brand Name : Latuda® Chemical Structure : Names of Student group in serial roll : Student name Serial roll 1- Abdelrahman Wageeh Ahmed 7631 2- Abdelaziz Fahmy Abdelaziz 7632 3- Abdelghany Hamed Abdelghany 7633 4- Abdelfatah Magdy Abdelfatah 7634 5- Abdullah Abdelnaby Hassan 7635 6-Abdullah Essam Mohamed 7636 7-Abdullah Mohsen Ragheb 7637 Under Supervision of : Dr/ Eman El-Bastawisy Dr/ Mervat El-Hamamsy Ph/ Salma El-Sherbiny
  • 2. 1- Generic / INN Name : Lurasidone 2- Brand Name : Latuda® 3- Chemical Name : (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)- piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7- methanisoindol-1,3-dione . 4- CASR # : 367514-88-3 5- Innovative Company & ( Country ) :  Dainippon Sumitomo Pharma Co., Ltd. Which is a pharmaceutical company based in Japan. Its headquarters are in Chuo-ku, Osaka.  Current Manufacturer is Sunovion Pharmaceuticals. 6- Chemical Structure :
  • 3. 7- Production : chemical synthesis. 8- Type ( Break Through, Me Too, New Indication, Others ): Me too 9- Class ( ATC Coding System ) : N05AH N Nervous System N05 Psycholeptics N05A Antipsychotics N05AH Diazepines , Oxazepines , Thiazepines , Oxepines. 10- Indications : Lurasidone is the newest atypical antipsychotic (AA) agent approved for the treatment of schizophrenia in adults. In clinical studies, Lurasidone alleviates positive (e.g., hallucinations, delusions) without inducing extra pyramidal side effects except for akathisia , despite its potent D2 antagonistic actions. Clinical evidence of Lurasidone's effect on negative symptoms of schizophrenia has yet to establish efficacy. Lurasidone may be useful for treating cognitive and memory deficits seen in schizophrenia for several reasons: 1) unlike many other antipsychotics, Lurasidone does not block the muscarinic acetylcholine receptors, an action well-known to impair learning and memory 2) Lurasidone has prominent activity at 5-HT1A, 5-HT2A, 5-HT7, and α2C- adrenergic receptors, all of which have been implicated in enhancement of cognitive function if modulated properly. In animal studies,
  • 4. Lurasidone was found to be superior to all of the other antipsychotics examined in reversing dizocilpine-induced learning and memory impairment, including risperidone, olanzapine, quetiapine, clozapine, aripiprazole, and haloperidol. 11- Dosage Form(s) & Presentation(s) : Lurasidone is available in 40-mg and 80-mg tablets. The recommended starting dose is 40 mg once daily, with a maximum dose of 80 mg/day. Higher doses provide no additional benefit and increase the incidence of certain adverse reactions. The dosage should not exceed 40 mg/day in patients with moderate-to-severe renal or hepatic impairment or in patients taking a moderate CYP3A4 inhibitor. Patients taking strong CYP3A4 inhibitors or inducers should not take Lurasidone. 12- Chemical Mode of action at receptor site : Receptor Binding Profile : Proposed mechanism of action of LATUDA * The lower the Ki Value, The higher the affinity. The mechanism of action of LATUDA, as with other drugs having efficacy in schizophrenia, is unknown. It has been suggested that the
  • 5. efficacy of LATUDA in schizophrenia is mediated through a combination of central dopamine D2 and serotonin 5HT-2A receptor antagonism. In vitro receptor binding of LATUDA The correlation between receptor binding affinities and clinical outcomes is uncertain . Lurasidone is an isoindole derivative that has a unique receptor- binding profile with high affinity for dopamine-2, serotonin- 2A, serotonin-7, serotonin-1A, and noradrenaline-2C receptors. These receptors are known to improve cognitive capabilities upon effective regulation. The drug has limited affinity for histamine-1 and acetylcholine- M1 receptors and is a partial agonist for the serotonin 5- hydroxytryptamine (5HT)1A receptor. Lurasidone enhances the functions of muscarinic acetylcholine receptors, which are known to aid in memory and learning functions.
  • 6. The dopamine D2-, D3-, D4 receptor There are two main subgroups of dopamine receptor – D1-like and D2-like. The D2- like family contains the D2, D3 and D4 subtypes and the D1-like receptor family contains the D1 and D5 receptor subtypes. The D2-like receptors are found throughout the brain and in smooth muscle and presynaptic nerve terminals. Coupled to inhibitory G-proteins, dopamine D2-like receptors have an inhibitory effect on neurotransmission when bound by an agonist. Many neuroleptic drugs are antagonists of the D2 receptors. This class of drug is used to treat psychotic disorders, such as schizophrenia. D2 receptor antagonist A D2 receptor antagonist prevents the activation of the dopamine D2 receptor. The D2 receptor is coupled to inhibitory G- proteins, which dissociate from the receptor on agonist binding and inhibit secondary messenger signaling mechanisms. This causes inhibition of down-stream signaling mechanisms. Antagonist binding inhibits this usual process, resulting in cell depolarization.
  • 8. 13- Pharmacophoric group : (1R,2S,6R,7S)-4-{[(1R,2R)-2-{[4-(1,2-Benzothiazol-3-yl)-1- piperazinyl]methyl}cyclohexyl]methyl}-4-azatricyclo[5.2.1.02,6]decane- 3,5-dione , structure shows 6 stereocenters that have major influence on its action as atypical antipsychotic drug . 14- Expected ADME Profile : - Absorption Lurasidone is absorbed and reaches highest concentration in 1-3 hours. Nine to 19 percent of oral administered dose is absorbed into the system. Its level is enhanced with food consumption. Cmax and AUC are increased by 3-times and 2-times, respectively, in the presence of food. - Distribution 98.8% of Lurasidone molecules is bound to plasma protein . - Metabolism Lurasidone is metabolized by CYP3A4 via oxidative N- dealkylation, hydroxylation and S oxidation. Major metabolites include two active and two non-active forms. - Elimination 80% is excreted in feces and 9% in urine.
  • 9. 15- Structures , Generic name(s) & Brand name(s) of related drugs : Generic Name Brand Name Structure Chloropromazine Largactil® (Sanofi Aventis) , Thorazine® (GlaxoSmithKline Haloperidol Haldol® (Janssen Pharm) , Serenace® (Pfizer) Quetiapine Seroquel® (Sun Pharma) Clozapine Clozaril® (Novartis) Olanzapine Zyprexa® (Eli Lilly) Aripiprazole Abilify ® (Bristol Myers Squibb)
  • 10. 16- SAR of drug relative to other available drugs for the same indication : Lurasidone is a chiral benzoisothiazol derivative - the benzoisothiazol is the fused five-six dual ring structure on the right of the figure. Its structure contains an imide heterocyclic and a piperazine functional group. The central piperazine nitrogen is basic. The chemical structure, properties and pharmacology are similar to Ziprasidone. 17- Advantages & Disadvantages of Drugs relative to other available drugs : - Favorable efficacy and safety profile than other antischizophrenic drugs. - LATUDA is contraindicated with strong CYP3A4 inhibitors (e.g., ketoconazole) and strong CYP3A4 inducers (e.g., rifampin). - Increased Mortality in elderly patients with Dementia – Related Psychosis (a severe mental health problem) . An increased risk for stroke and mini stroke has been reported in elderly people with dementia-related psychosis. - Neuroleptic malignant syndrome (NMS): High fever; stiff muscles; confusion; changes in pulse, heart rate, or blood pressure; sweating; or muscle pain and weakness. Treatment should be stopped if you have NMS. - Tardive dyskinesia (TD): TD is a serious and sometimes permanent side effect reported with LATUDA and similar medicines. TD includes uncontrollable movements of the face, tongue, and other parts of the body. The risk for developing TD and the chance that it will become permanent is thought to increase the longer a person takes the medicine and the more medicine a person takes over time. TD can develop after a person has been taking the medicine for a short time at low doses, although this is much less common. There is no known treatment for TD, but it may go away partially or completely if the person stops taking the medicine.
  • 11. - Metabolic changes : a) High blood sugar. b) High cholesterol and triglycerides. c) Weight gain. 18 Future Outlook : Latuda is predicted to be the number one selling atypical antipsychotic drug in the upcoming new years . Latuda binding to receptor may be enhanced to gain more efficiency and potency , may some modification make more potent drug and modify the partial agonist activity of the drug on the serotonin 5-hydroxytryptamine (5HT)1A receptor . Additional research is running to help developing the drug as third generation atypical antipsychotic drug. 19- References : www.wikipedia.org www.fda.gov www.Latuda.com www.latudahcp.com www.medscape.com www.chemspider.com www.Drugbank.ca www.chemdrug.com www.dailymed.nlm.nih.gov Journals : NDA Application number (200603) Medical Reviews. NDA Application number (200603) Chemical Reviews. NDA Application number (200602) Proprietay Name Reviews. Latuda Prescribing Information ( Available on www.Latudahcp.com )