cholinergic drugs
DESCRIPTION
Cholinergic drugs. Nervous system. CENTRAL NERVOUS SYSTEM PERIPHERAL NERVOUS SYSTEMS Sensory fiber motor fiber involuntary voluntary sympathetic parasympathetic. function. - PowerPoint PPT PresentationTRANSCRIPT
Cholinergic drugs
Nervous system
CENTRAL NERVOUS SYSTEM PERIPHERAL NERVOUS SYSTEMS
Sensory fiber motor fiber
involuntary voluntary sympathetic parasympathetic
function
Sympathetic and parasympathetic are complemantary
Composition: pre,ganglion and post Chemicals are Ach and NA
Cholinergic drugs
Drugs produce similar effects to acetylcholine
Classification
a. Direct cholinergic agents
b. Indirect
c. Cholinestrase reactivator
Effects of acetylcholine
A. Muscarinic effects Contaraction of smooth muscle Peripheral vasodilation Increase secretion of saliva, exocrine Dcrease the contraction of the heart
B. Nicotinic Stimulation of skeletal muscle tone
Trans acetylcholine active on muscarinic and nicotinic receptors
A. Direct cholinergic agents
Mode of action
Choline esters Cholinomimetic alkaloid
Methacholine
Carbachol
[Cholinomimetics & parasympathomimetics]
Pilocarpine
SAR
CH3
N+
O CH3
OCH3
CH3
Acetyl choline
Metacholine
CH3
N+
O CH3
OCH3
CH3
CH3
• CH3 on beta carbon increase muscarinic
• Long duration
• Uses: Mythenia gravis, paroxysmal tachycardia
Synthesis
O
+ N
HO
CH3
N+
O
CH3
N
O
Carbachol
Long duration Uses: glucoma Synthesis
CH3
N+
O NH2
OCH3
CH3
Bethanicol
Bioisoster of methacholine
Long durationMainly muscarinic
Uses:abdominal distention,urinary distention
O
CH3
N
O
H2N
2 .Cholinomimetic alkaloid
pilocarpine
O
N
NO
CH3
CH3
Uses: glucoma, antagonises mydriatics
cevimeline
For treatment of dry mouth in Sjogren’s syndrome
Similar to pilocarpinO
S
N
B.Indirect acting [anticholinesterase]
Carbamates
Physostigmine
Neostigmine methyl sulphate
Pyridostigmine
Neostigmine bromide(prostigmin)
Edrophonium
Organophosphorus
Physostigmine acts by interfering with the metabolism of acetylcholine. It is an inhibitor of acetylcholinesterase, the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft of the neuromuscular junction. It indirectly stimulates both nicotinic and muscarinic receptors. (Find the structure and uses).
Neostigmine bromide(prostigmin)
N+
CH3
CH3O
O
NCH3
CH3
CH3
Synthesis
OH OH
+ NH
CH3
CH3
OH N
CH3
CH3
O
Cl Cl
N
CH3
CH3O
O
ClNH
CH3
CH3
N
CH3
CH3O
O
NCH3
CH3
CH3Br
N+
CH3
CH3O
O
NCH3
CH3
CH3
Br-
III
IIIIV
V
Neostigmine methyl sulphate
Uses Contraindication
Bradycardia, cardiac disease, hypotension, parkinsonism.
Pyridostigmine bromide(mestinon)
N
O
O
N
B r+
Synthesis
Uses: Mysthenia gravis
N
OH+ C l
O
N
N
O
O
N CH3
Br
N
O
O
N
B r+
I II IVIII
Edrophonium Chloride
Short and rapid-acting cholinergic drug .Uses:myasthenia gravis , emergency treatment (short action)
Side effects: bradycardiaa, hypotension,increase saliva
Cholinesterase reactivators
N+
CH3
NOH
2)]-Hydroxyimino(methyl-[1-methylpyridinium chloride
Synthesis
NC l
+ N NH
+ OH
(I) (II)
-H2O
NN H
+
(III)
N N+ O H
NH2OH.HCl
Cholinergic blocking agents[Anticholinergic]
Act at different sites
Postganglionic of parasympathetic(Antimuscurinic)
At ganglionia of sympathetic and parasympathetic
(ganglion blockers)
Neuromuscular junction of voluntry system
(neuromuscular blocking agents)
I. Antimuscarinics[similar to Ach & alkaloid]
There effects will be : Mydriatic Antispasmodic antisecretory
1. Antimuscarinics similar to Acetyl choline
R C O (CH2)n N
O
5 AAntimuscarinic:aminoalcohol,aminoamides,
papaverine derivatives.Aminoalcohols:esters,ethers,carbamates.
Esters:solaneceous alk.,synthetic analouges,esters of other alc.
2 .Alkaloid antimuscarinics
Atropine, Hyoscin
Uses of Antimuscarinics:
Antispasmodic
Antisecretory
Antiparkinsonism
mydriatics
Esters of other aminoalcohol
CyclopentolateUses:
mydriatic ,cycloplegicN
O
OOH
2-(dimethylamino)ethyl 2-(1-hydroxycyclopentyl)-2-phenylacetate
Aminoalcohol ethers
OrphenadrineUses:
Antihistaminic,antiparki-nsonism.
N
O
N,N-dimethyl-2-(phenyl(o-tolyl)methoxy)ethanamine
Oxybutynin
used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination
Homework : find the structure and mechanism of action
Papaverine and related compounds .
N
H3CO
H3CO
OCH3
OCH3
Vasodilator relax smooth muscle.(GIT,bronchi,uretures,biliary system).
Trihexyphenidyl
Uses Parkinson’s disease
OH
N
1-cyclohexyl-1-phenyl-3-(piperidin-1-yl)propan-1-ol
Ipratropium bromide
Uses Bronchodilator
Ganglionic blocking agent
Hexamethonium
N+
N+ Cl-
Cl-
Neuromuscular bloking agents
Decamethonium bromide
Assay :volhard
N+
N
Br-
Br-
+
Neuromuscular blocking agents
C
C
O
O
O
O
N+
N+ Cl-
Cl-
Succinylcholine
ON+
ON+
O
N+
3I-
gallamine triethiodide
Uses