cholinestrases, mechanism of action

1. Cholinestrases
Submitted to:-
Prof. Narsimahan B.
Submitted by:-
Mukesh kumari
M. Pharmacy, 2nd sem.
Roll no.- 1840
Pharmaceutical chemistry

2. Cholinestrase
• A family of enzymes (esterase) that lyses choline based esters i.e. neurotransmitters.
• Present in central nervous system, particularly in nervous system, muscles and red cells.
• breaking acetyl choline into choline and acetic acid.
• Reactions are necessary to allow neuron to return to its resting state after activation.

3. Types of Cholinestrase
Two type of cholinesterase are:-
(false or pseudocholinestrase,cholinestrase-2,
plasma cholinestrase, serum cholinestrase)
 Found in liver and in blood plasma
 Butyl and butyryl syllables both refers to butane
with one of its terminal methyl group
substituted.
Acetyl-cholinestrase
(ACHE)
Butyryl-cholinestrase
(BCHE)
(True cholinestrase, RBC or erythrocyte
Cholinestrase, acetylcholine acetylhydrolase)
 Found in RBC, neuromuscular junction and
neural synpases.
 Exist in multi-molecular form.
 In mammalian brain , found in tetrameric
G4 form.

4. O
N
O
+
Acetylcholine
N
OH X
+ _
Choline
OH
O
Acetic acid
N
O
O
+
Butyrylcholine

5. Mechanism of action (cholinestrase):-

7. Anticholinestrases
Reversible Irreversible
Carbamates Acridine Organophosphates Carbamates
 Physostigmine
 Neostigmine
 Pyridostigmine
 Edrophonium
 Rivastigmine
 Donepezil
 Galantamine
 Tacrine  Dyflos
 Ecothiophate
 Malathion *
 Diazinon *
 Tabun £
 Serin £
 Soman £
 Carbaryl *
 Prooxur *
* Insecticide
£ nerve gas for chemical warfare

8. Mechanism of action (Anticholinestrase):-

11. Carbamates
 derived from Carbamic acid ( NH2COOH ).
 Structure of biologically active carbamates is….
Here,
X = can be oxygen or sulphur
R1 and R2 = organic and alkyl substituents
R3 = mostly an organic substituent
N
R1
X
R3
R2
X

12. 1. Physostigmine:-
 An alkaloid obtained from Physostigma Venenosum seeds. N
N
O C O N H C H 3
C H 3
H
C H 3
H 3C
MOA:-
At the body fluids pH,
Physostigmine
Protonated at N and form complex with active site of acetylcholinestrase
Cleavage of carbamate ester moiety
Transfer of N-methyl carbamoyl moiey to hydroxyl of Serine residue takes
place

13. 2. Neostigmine:-
 Quaternary ammonium synthetic analogue
Synthesis:-
N
OCON(CH3)2Br-
CH3H3C
CH3
+
N(CH3)2
OH
+ ClCON(CH3)2
N(CH3)2
OCON(CH3)2
CH3Br
m-dimethyl-aminophenol
Neostigmine Bromide

14. Organophosphates
 Esters or thiols derived from phosphoric, phosphonic, phosphinic or phosphoramidic acids.
P
X
R 2R 1
O
Here,
 R1 and R2 are aryl groups that are bonded phosphorus atom either directly or through an oxygen or
sulphur.
 X = halogen, aliphatic, aromatic and heterocyclic groups.
 Leaving group is released from phosphorus atom when OP is hydrolysed by phosphotriesterases.

15. N
C H 3
H 3 C
C H 3
C H 2 C H 2 S P
O C H 2 C H 3
O C H 2 C H 3 I-
O
+
E c o th io p a te I o d id e
P C N( H 3 C ) 2 N
O C H 2 C H 3
O
T a b u n
P FH 3 C
O C H (C H 3 ) 2
O
S a r in e
P FH 3 C
O C H C H 2 ( C H 3 ) 3
O
C H 3
S o m a n

16. OR
PH3C
X
O + EOH
O
PH3C
X
O-
E
RO
O
PH3C
OR
O
E
+ X-
OR
PH3C
ONR
O
OR
PH3C
OH
O
O
PH3C
O-
O
E
+ EOH
+ EOH + ROH + H+
H2O
R=NOH
R=NOH
Reactivation
Spontaneous hydrolysis
Ageing
Mechanism of action:-

17. Uses or Applications:-
 Occur naturally venoms and poisons.
 As insectisides.
 To treat myasthenia gravis.
 To treat glaucoma.
 As an antidote to anticholinergic poisoning.

18. References:-
 Singh Harikishan and Kapoor V.K., “Medicinal and Pharmaceutical Chemistry”, First Edition, Published
by- Vallabh Prakashan, Page no.- 211-217.
 Tripathi K.D., “Essentials of Medicinal Pharmacology”, Seventh Edition,Published by-Jaypee Brothers
Medical publishers(P)LTD, Page no. – 105-109.
 http://www.ncbi.nlm.nih.gov/pmc/artical/pmc3648782/as dated on 14/02/018.
 http://www.ncbi.nih.gov/pmc/artical/pmc4100123/as dated on 14/02/018.
 http://en.wikkipedia.org/wiki/Acetylcholinestrase-inhibitor as dated on 14/02/018.
 http://www.sciencedirect.com/topic/neuroscience/anticholinestrases as dated on 14/02/018.

19. Thank you