1. Medicinal chemistry l
Lecture 10
Para-Sympathomimetic agents –Indirect acting agents
• By Manjusha SK
• Associate professor
2. Para-Sympathomimetic agents
Introduction –
Parasympathomimetic agents are the compounds which mimic the actions of acetyl choline and causes
nerve stimulation.
The acetyl choline is the major neurotransmitter.
These agents are further divided into two types,
1.Direct acting para-sympathomimetics : These drugs bind to the nicotinic or
muscarinic receptors and causes excitation of cholinergic system.
2.Indirect acting para-sympathomimetics : These drugs inhibit the hydrolysis of
acetylcholine and hence increases the life of acetylcholine.
So it causes increased concentration of ACh at the receptor site to produce excitation of cholinergic
system.
These agents are also known as anticholinesterases.
4. PARA-SYMPATHOMIMETIC AGENTS (drugs) – B) Indirect acting agents –
Introduction -These agents are also known as acetylcholinesterase inhibitors.
The acetylcholinesterase inhibitors inhibits me ACh enzyme and cause accumulation of ACh in vicinity of
cholinergic nerve terminals.
So this higher concentration of the neurotansmitter increases the biological response.
These agents are of two types :
1) Reversible Inhibitors- As thé name indicates, these drugs binds riversibly to the choline subsite.
These agents form an ester like carbonate or phosphate and covalently binds to
the active site of enzyme. For example, Physostigmine and Neostigmine
2) Irreversible Inhibitors – These drugs binds irriversibly by covalently bonding to the
active site of enzyme. These drugs produces irreversible inactivation
of acetylcholinesterase.
This category includes various organophosphorous compounds.
For example, Parathion,Malathion.
5. Various drugs belonging to Indirect Acting Agents are as bellow,(Reversible Inhibitors- )
1) Physostigmine salicylate –
Structure –
Mechanism of action - Physostigmine is a reversible tertiary amine inhibitor of cholinesterase.
The cholinesterase activity similar to the neostigmine.
Uses – Used as miotics (causing constriction of the pupil of the eye) to decrease
interaocular pressure in glaucoma.
Used parentrally for reversal effects caused by anticholinergic and antidepressants.
2) Neostigmine Bromide –
Synthesis –
6. 2) Neostigmine Bromide –
Mechanism of action – Neostigmine indirectly stimulates
both muscarinic and nicotinic receptors.
It binds to the anionic and esteric site of cholinesterase
and block the activity of acetychlolinesterase.
Uses – Used in the treatment of myasthenia gravis.
(weakness of muscles)
Used in the treatment of paralytic ilens.
(muscle movement of food through your intestines
are temporarily paralyzed).
3)Pyridostigmine - Structure –
Mechanism of action – It works by blocking the action
of acetylcholinesterase and therefore
increases the levels of acetylcholine.
Uses - Used in the treatment of myasthenia gravis.
(weakness of muscles)
used in the prophylaxis of nerve gas poisoning.
used in the management of postoperative urinary.
7. Various drugs belonging to Indirect Acting Agents are as bellow,(Irreversible Inhibitors- )
1) Parathion –
Structure –
Mechanism of Action - It indirectly acts on acetyl cholinesterase enzyme.
Uses -It is used as insecticide in agriculture. It is often -applied by spraying to cotton,rice and fruit trees.
2) Malathion –
Structure –
Mechanism of Action – It act by irreversibly inhibiting the activity of cholinesterase, thereby allowing
acetylcholine to accumulate at cholinergic synapses and enhancing cholinergic receptor stimulation.
Uses – Used in treatment of head lice and body lice. Used as insecticide.
It is also used in the treatment of scabies (a skin disease-small red spots and want to rub or scratch it)
8. PARA-SYMPATHOMIMETIC AGENTS (drugs) – C) Cholinesterase Reactivator –
These are the drugs which causes the reverse of the inactivation of cholinesterase.
Means these agents causes reactivation of cholinesterases.For example ,Pralidoxime chloride .
1) Pralidoxime chloride –
Structure -
Mechanism of Action – It reactivate the acetyl cholinesterase enzyme rapidly by binding to the
anionic site of enzyme and displaces phosphate from the serine residue.
Uses – It is mainly used in the treatment of poisoning by organophophorous compounds.
(Organophosphorus compounds (OPCs) are organic chemicals derived from phosphoric acids and its derivatives
and contain at least one carbon-phosphorus bond.)
Used in the treatment of overdose caused by anticholinesterase drugs,neostigmine.
