This document discusses cholinesterases, which are a family of enzymes that break down acetylcholine in the nervous system. There are two main types of cholinesterases: acetylcholinesterase and butyrylcholinesterase. Acetylcholinesterase is found primarily at neuromuscular junctions and neural synapses, while butyrylcholinesterase is found mainly in the liver and blood plasma. Cholinesterases break down neurotransmitters like acetylcholine to allow neurons to return to their resting state. The document also discusses anticholinesterases like carbamates and organophosphates, which act to inhibit cholinesterase activity. Common carbam

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