Parasympathomimetics Agent {Cholinergic Drug}

Parasympathomimetic Agent_Medicinal Chemistry I _ B. Pharma (2nd Year)_ 4th Semester
Overview:-
SAR _Parasympathomimetic agent
Classification

1. Presentation Topic 1 . Parasympathomimetc Agent Medicinal Chemistry 1

2. Parasympathomimetic Agent Also Called as Cholinergic Agonists / Cholinergic Drugs Parasympathomimetic – Parasympotho means Parasympathetic Nervous System & Mimetic means copy Drugs that activate muscarinic receptors in the Peripheral Nervous system is called as Parasympathomimetic drugs. Because they mimic the effect of acetylcholine on Parasympathetic Nervous System. Parasympathomimetic agent are those chemical drugs which copy the action of Parasympathetic Nervous System. T here drugs bind with Cholinregic receptor (M & N) & give action. ( they Act as cholinergic Neurotransmitter). S AR of Parasympathomimetic Agents SAR -> Structure Activity Relationship It is defined as the relationship between the chemical structure of a molecules & its biological activity. This allows modification of the effect or potency of a substance by changing its chemical structure.

3. Paraympathomimetic Agent Overview Definition Classification Structure Mechanism of Action Uses

4. Classification of Parasympathomimetic Agent Acetylcholine Carbachol Bethanechol Methacholine Pilocarpine Direct Acting Indirect Acting Reversible Physostigmine Neostigmine Pyridostigmine Edrophonium chloride Tacrine Hydrochloride Ambenonium Chloride Irreversible Isofluorphate Ecothiophate iodide Parathione Malathion Cholinesterase reactivator Pralidoxime chloride

5. Direct Acting Agent Acetylcholine Mechanism of Action :- Chemical Formula – C 7 H 16 NO 2 It is Direct Acting Cholinergic Drug. It is powerful but its action is destructed by cholinesterase. Uses :- W idely used as eyedrop to cause miosis during surgery & recover. U sed as vasdilator & Cardiac Depressent etc. Carbachol Mechanism of Action:- Bind with both muscarinic & nicotinic . It is not inactivated by cholinersterase so its action are more prolonged than acetylcholine. Uses :- Chemical Formula :- C 6 H 15 CIN 2 O 2 Used in case of severe chronic glaucoma. G ive intra-ocularly to produce miosis in ocular surgery & to reduce post operative risk. T hese are those which directly bind with cholinergic receptor (N & M) & give its action.

6. Bethanechol Mechanism of Action :- Chemical Formula - C 7 H 17 N 2 O 2 More selective on the muscarinic receptors. It is more stable than Carbachol due to presence of methyl group on β -carbon. Uses:- Used to stimulate GIT & urinary bladder after surgery. Prolong effect than acetylcholine. Methacholine Mechanism of Action:- Chemical Formula - C 8 H 18 NO 2 It has muscarinic actions of acetylcholine. Prolonged action than acetylcholine. Uses :- Used in the treatment of Reynaud's syndrome & Glaucoma. Used in Case of Tachycardia Pilocarpine Mechanism of Action:- Direct Acting cholinergic drug that has muscarinic effect of acetylcholine.

7. Indirect Acting Agent Or Cholinesterase Inhibitors Uses:- Chemical Formula – C 11 H 16 N 2 O 2 Used in treatment of glaucoma & in treatment of dry eye or dry mouth. Used before surgery as part of emergency treatment of acute attack of angle closure glaucoma. Also called as anticholinesterases. These are those drug which does not directly act on receptors but inhibit the hydrolysis of acetylene by acetyl cholinesterases & hence increase the life of acetylcholine, so acetylcholine give their action. There are 2 types Reversible Inhibitors Irreversible Inhibitors Reversible Inhibitors These are those drugs which binds reversibally to the acetylcholinesterase enzyme. These drugs form an ester like carbonate or phosphate & bind with active site of enzyme. Now this enzyme does not hydrolyzed acetylcholine so increase in the concentration of acetylene. Physostigmine Mechanism of action :- Reversible Cholinesterase Inhibitor. It indirectly stimulate both Muscarinic & Nicotinic receptors. Uses :- Chemical Formula – C 15 H 21 N 3 O 2 Used as a miotic Used to intraocular pressure in glaucoma decrease.

8. Neostigmine Mechanism of Action:- Chemical Formula – C 12 H 19 N 2 O 2 I t indirectly stimulates both muscarine & nicotonic receptors. I t bind to the anionic & esteric site of cholinesterase & block the activity of acetylcholinesterase . U ses:- Used in the treatment of neyasthenia gravis. A lso used in glaucoma (lower intraocular pressure) Pyridostigmine Mechanism of action:- B lock acetyl cholinesterase enzyme & inhibit the destruction of released acetylcholine. I t is a quaternary carbamate about 30% of peripheral cholinesterase enzyme. U ses:- Chemical Formula – C 9 H 13 N 2 O 2 U sed in the treatment of myasthenia gravis. A lso helpful in nerve gas poisoning . Edrophonium Chloride Mechanism of Action:- Reversible Cholinergic Inhibitor Short duration of action than neostigmine & pyridostigmine. A cetylcholine stimulates nicotinic & muscarinic receptors. Uses:- U seful for the treatment of myasthenia gravis (not for regular). U sed in the treatment of snake bite. Chemical Formula – C 10 H 16 ClNO

9. Tacrine Hydrochloride Mechanism of action:- Chemical Formula – C 13 H 15 ClN 2 C entrally acting anticholinesterases. T acrine also inhibits butyryl cholinesterase activity. U ses :- U sed for the treatment of Alzheimer’s disease. Ambenonium Chloride Mechanism of action :- Reversibly inhibit acetylcholine. Uses:- Used in the treatment/management of myasthenia gravis. Irreversible Inhibitors These are those drug which produces irreversible inactivation of acetylcholinesterase enzyme. These drugs bind irreversibly by covalent bond to the active site of enzyme. This category include various organophosphorus compound. Isoflurophate Chemical Formula – C 6 H 14 FO 3 P Mechanism of action :- Irreversible inactivation of the acetyl cholinesterase.

10. Uses:- Used as miotic agent in treatment of glaucoma. Ecothiophate Iodide Mechanism of action :- Irreversible acetyl cholinesterase inhibitor. P ermanently inactive the enzyme. T he pupil of the eye is constricted by contraction of the iris sphincter, producing miosis. Chemical Formula – C 9 H 23 INO 3 PS Uses:- Used as an ocular antihypertensive in the treatment of chronic glaucoma. I t is ophthalmic (for the eye) reduces pressure in the eye. T his medicine also used to treat certain eye focusing disorders. Parathione Chemical Formula – C 10 H 14 NO 5 PS Mechanism of action :- Indirectly inhibitor It is absorbed via skin, mucous membranes & orally. A bsorbed parathion is rapidly metabolized to paraoxon as described in Insecticdal activity. Uses :- Used as insecticde in agriculture . It is pale yellow to brown liquid with an odor like garlic . Used by farmers as a pesticide on fruits, vegetables, nuts & grains.

11. Malathion M echanism of action :- B inding serine residue on cholinesterase enzyme & inactive it irreversily . T his eventually leads to the head lice’s death. Uses:- Chemical Formula – C 10 H 19 O 6 PS U sed for treatment of scabies. U sed as insecticide. M alathion lotion is used to treat head lice in adults & children 6 years of age & older. I t should not be used in infants & children younger than 2 years of age. I t is in a class of medication called pediculicide. I t works by killing lice. Cholinesterase Reactivators These are those drugs which cause reactivation of cholinesterase enzyme. These are mainly used in the treatment of poisoning by organophosphates, sulphonates & acetylcholinesterase inhibitors. Pralidoxime chloride Mechanism of action :- Chemical Formula – C 7 H 9 ClN 2 O It reactivate the enzyme by binding anioic site of enzyme & displaces the phosphate from the serine residue. Uses:- U sed for the treatment of poisoning by organophosphorus compounds.