DIAZEPAM, OXAZEPAM, ALPRAZOLAM AND QUETIAPINE WITH THEIR MECHANISM OF ACTION.

1. UNIVERSITY OF KOTA,
KOTA(Raj.)
SESSION - 2018
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2. SUBMITTED TO-
PREPARED BY-
DATE :- 13/04/2018
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3.  ACKNOWLWDGEMENT
 ANTIPSYCHOTICS
 STUDY OF SYNTHESIS OF THE FOLLOWING ATYPICAL ANTIPSYCHOTIC DRUGS :-
 DIAZEPAM
 OXAZEPAM
 ALPRAZOLAM
 QUETIAPINE
 MECHANISM OF ACTION :-
 STRUCTURE OF NEURON
 GENERATION AND CONDUCTION OF NERVE IMPULSE
 TRANSMISSION OF IMPULSE
 GABA AND BENZODIAZEPINE RECEPTOR COMPLEX
 MECHANISM OF ACTION OF BENZODIAZEPINES (DIAZEPAM, OXAZEPAM & ALPRAZOLAM)
 FLOWCHART
 MECHANISM OF ACTION OF QUETIAPINE
 REFRENCES
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4. I would like to express my deep gratitude to
Professor BHAWANI SINGH for their patient guidance and
enthusiastic encouragement. My grateful thanks are also
extended to Dr SHWETA VYAS MA’AM for her advice and
support.
Finally, I wish to thank my parents for their support and
encouragement throughout my study.
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6.  Antipsychotics, also known as neuroleptics or major tranquilizers, are a
class of medication primarily used to
manage psychosis (including delusions, hallucinations, paranoia or disordered
thought), principally in schizophrenia and bipolar disorder.
 Antipsychotics are usually effective in relieving symptoms of psychosis in the short term.
 First-generation antipsychotics, known as typical antipsychotics,were discovered in the
1950s.
 Most second-generation drugs, known as atypical antipsychotics, have been developed
more recently
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8.  Diazepam, first marketed as Valium, is a medication of the benzodiazepine family that typically produces a
calming effect.
 it is commonly used to treat a range of conditions including anxiety, alcohol withdrawal
syndrome, benzodiazepine withdrawal syndrome, muscle spasms, seizures, trouble sleeping, and restless
legs syndrome.
 It is a broad spectrum drug.
 It may also be used to cause memory loss during certain medical procedures.
 It can be taken by mouth, inserted into the rectum, injected into muscle, or injected into a vein.
 When given into a vein, effects begin in one to five minutes and last up to an hour. By mouth, effects may
take 40 minutes to begin.
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9. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
(DIAZEPAM)
Cl
6
7
8
9
N
N
CH3
O
1
2
3
4
5
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10. It can be synthesized by acetylation of the aminobenzophenone with chloro acetyl chloride, which gives an amide. By
heating this amide with ammonia or it’s latent equivalent, hexamethylenetetramine (HMTA), chlorine is displaced and
glycineamide is formed. It’s cyclization gives diazepam in the following manner :-
O
NHCH3
Cl ClCOCH2Cl Cl
N
O
Cl
OCH3
or HMTA
Cl
N
N
OCH3
Aminobenzophenone
Diazepam
NH3
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11.  Oxazepam is a short-to-intermediate-acting benzodiazepine.
 It is a CNS depressant drug.
 Oxazepam is used for the treatment of anxiety and insomnia and in the
control of symptoms of alcohol withdrawal.
 It is a metabolite of diazepam, prazepam, and temazepam, and has
moderate amnesic, anxiolytic, anticonvulsant, hypnotic, sedative,
and skeletal muscle relaxant properties compared to other
benzodiazepines.
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12. 7-chloro-3-hydroxy-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one
OXAZEPAM
Cl
N
N
H
O
OH
1
2
3
456
7
8
9
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13. Acetylation of demoxepam followed by hydrolysis gives oxazepam in the following manner :-
Cl
N
N
H
O
O
(CH3CO)2O
Cl
N
N
H
O
OCOCH3
H2O
Cl
N
N
H
O
OH
1 2
3
4
5
2C
3C
4C
6
7
8
9
Demoxepam
Oxazepam
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14.  Alprazolam, is a potent, short-acting benzodiazepine anxiolytic—a minor tranquilizer.
 It is commonly used for the treatment of anxiety disorders, especially of panic disorder,
but also in the treatment of generalized anxiety disorder (GAD) or social anxiety disorder.
 Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA receptor.
 It possesses anxiolytic, sedative, hypnotic, skeletal muscle
relaxant, anticonvulsant, amnestic, and antidepressant properties.
 Alprazolam is available for oral administration as compressed tablets (CT), orally
disintegrating tablet (ODT) and extended-release tablets (XR).
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15. Cl
N
N
N
NH3C
8
67
1
2
3
4
5
9
10
Alprazolam
8-Chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a] [1,4]benzodiazepine
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16. With phosphorus penta sulphide nordazepam forms a thioamide which, with hydrazine, gives the versatile
intermediate amidine. It gives alprazolam by using methyl orthoacetate.
C l
N
N
H
O
P 2 S 5
C l
N
N
H
S
N H 2 N H 2
C l
N
N
N H N H 2
C l
N
N
N
NH 3 C
N o r d a z e p a m T h i o a m i d e
a m i d i n eA l p r a z o l a m
C H 3 C ( O C H 3 ) 3
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17. Quetiapine, is an atypical antipsychotic drug.
It is used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder.
It is also sometimes used as a sleep aid due to its sedating effect, but this use is not
recommended.
Quetiapine is believed to work by blocking a number of receptors
including serotonin and dopamine receptors. (SDA antagonist)
It is taken by mouth.
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18. O
N
N
S
N
OH
2-(2-(4-Dibenzo[b,f][1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol
QUETIAPINE
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19. The synthesis of quetiapine begins with a dibenzothiazepinone. The lactam is first
treated with phosphoryl chloride to produce a dibenzothiazepine. A nucleophilic
substitution is used to introduce the sidechain.
Dibenzothiazepinone
1-(piperazinyl)ethoxy ethanol
Quetiapine
Chloro dibenzothiazepine
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20. The following points are really important to understand mechanism of
psychoactive drugs :-
STRUCTURE OF NEURON
GENERATION AND CONDUCTION OF NERVE IMPULSE
TRANSMISSION OF IMPULSE
GABA AND BENZODIAZEPINE RECEPTOR COMPLEX
MECHANISM OF ACTION OF BENZODIAZEPINES
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22. (AXOLEMMA)
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23. A. AT REST :- POLARISED STATE
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24. B. DEPOLARIZATION:-
C. REPOLARIZATION:-
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25. -60
-70
(NA-CHANNELS OPEN)
(K-CHANNELS OPEN)
-80 mV
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28.  In the CNS, the benzodiazepines interect with a macromolecular membrane complex which also has
a recognition site for GABA (gamma-aminobutyric acid) and a chloride ionophore.
 Benzodiazepines act preferentially on mid brain ascending reticular formation (which maintains
wakefulness) and on limbic system (thought and mental functions).
 Muscle relaxation is produced by a primary medullary site of action and ataxia is due to action on
cerebellum.
 Benzodiazepines work by increasing the efficiency of a natural brain chemical, GABA, to decrease
the excitability of neurons. This reduces the communication between neurons and, therefore, has a
calming effect on many of the functions of the brain.
 GABA controls the excitability of neurons by binding to the GABAA receptor. The GABAAreceptor is
a protein complex located in the synapses of neurons.
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29.  All GABAA receptors contain an ion channel that conducts chloride ions across neuronal cell
membranes and two binding sites for the neurotransmitter gamma-aminobutyric acid (GABA),
while a subset of GABAA receptor complexes also contain a single binding site for
benzodiazepines.
 Binding of benzodiazepines to this receptor complex does not alter binding of GABA. Unlike
other positive allosteric modulators that increases ligand binding, benzodiazepine binding acts
as a positive allosteric modulator by increasing the total conduction of chloride ions across the
neuronal cell membrane when GABA is already bound to its receptor.
 This increased chloride ion influx hyperpolarizes the neuron's membrane potential. As a result,
the difference between resting potential and threshold potential is increased and firing is less
likely.
 Different GABAAreceptor subtypes have varying distributions within different regions of the
brain and, therefore, control distinct neuronal circuits. Hence, activation of different
GABAA receptor subtypes by benzodiazepines may result in distinct pharmacological actions.
 In terms of the mechanism of action of benzodiazepines, their similarities are too great to
separate them into individual categories such as anxiolytic or hypnotic. For example, a
hypnotic administered in low doses produces anxiety-relieving effects, whereas a
benzodiazepine marketed as an anti-anxiety drug at higher doses induces sleep.
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32. • It’s actual mechanism is unknown.
• But some scientists suggested that it inhibits the reuptake of dopamine and norepinephrine like inhibitory
neurotransmitters and potent their function by negative allosteric effect as shown in following video:--
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33. ALKA L. GUPTA, MEDICINAL CHEMISTRY, PRAGATI
EDITION
WIKIPEDIA
SLIDESHARE.COM
VIDEO LECTURES BY Dr. RAJEEV RAJAN
NEETPREP, YOUTUBE CHANNEL
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