THIRD GENERATION

ANTIPSYCHOTICS ???

By-
V.Janarthana
Atypical antipsychotics - review
S.No. DRUG TRADE NAME FDA APPROVAL
SCZ BPAD
1 Clozapine Clozaril 1989 NA

2 Risperidone Risperdol 1993 2001

3 Olanzapine Zyprexa 1993 2004

4 Quetiapine Seroquel 1997 2004

5 Ziprasidone Geodon 2002 2006

6 Aripiprazole Abilify 2002 2004

7 Paliperidone Invega 2007,April NA

8 Amisulpride Solian Approved in Europe,

Australia, etc.
 CLOZAPINE

Marked agranulocytosis and seizures.

 RISPERIDONE

Increased prolactin level and reproductive

problems.
OLANZAPINE

Marked weight gain.

QUETIAPINE

Most sedating.
 ZIPRASIDONE

QT interval prolongation and sedation.

Weight neutral
Used i.m. in acute agitation.
ARIPIPRAZOLE

Weight gain

Selective dopamine antagonist

PALIPERIDONE

Increases prolactin level.

 ATYPICAL
ANTIPSYCHOTICS
PROS:
1. No EPS
2. Also used in personality disorders, mania,
depression, BPAD, etc.
CONS:
1. Obesity
2. Diabetes
3. Raised cholesterol level
4. Heart diseases
CONTROVERSY
Are atypical
antipsychotics
superior over the
classical ones
 BL-1020
Firm : BioLine Rx

Inventors : Dr.Abraham Nudelman

Dr.Ada rephaeli
Dr.Irit Gil

Progress : Completed phase II-b clinical trials

under FDA-IND application.
 BL-1020
Areas covered : U.S., Europe and India.

Final results : August, 2009

Specialty : GABA enhanced

Acts at GABA-a receptors
 BL-1020
Star feature : First drug with the potential to
improve cognition in
schizophrenia.

Advantages : Increased patient compliance,

More efficacy and tolerability,
Also used in dementia associated
with Parkinsonism and
Adjunct in Alzheimer's disease.
N- DESMETHYL CLOZAPINE

Inventors : Dr. Sridhar Natesan

Dr. Greg E Reckless
Dr. Karen B l Barlow
Dr. Jose N Nobrega
Dr. Shitij Kapur
N- DESMETHYL CLOZAPINE

Action : 5HT2 antagonist,

Partial agonist at D2 and
Partial agonist at muscarinic.

Chemistry : NDMA is an active

metabolite of clozapine.
 MLC 1 Gene

Location : 22 q 13.33

Putative role : Product may be a integral

membrane cation channel.

Significance : Associated with schizophrenia in

southern parts of India.
 MLC 1 Gene

Researchers : Dr. Verma Ranjana

Dr. Mukerji Mitali
Dr. Grover Deepak
Dr. B Rao Chandrika
Dr. Das Swapan kumar
Dr. Kubendran
Dr. Shobana
Dr. Jain Sanjeev
Dr. Brahmachari Samir K
 MLC 1 Gene

Findings :
1. 33 sequence variations in MLC 1.
2. 3 novel mutations:
- Val210Ile
- Leu308Gln
- Arg328His
3. Most are missense mutations.
SHOULD ALL PSYCHOTIC CONDITIONS BE TREATED