Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.

1

Muscarinic AgonistsNatural Alkaloids:

MuscarinePilocarpineArecholine

Synthetic Alkaloid:Oxotramorine

Mainly Nicotinic AgonistsNatural Alkaloids:

NicotineSynthetic Alkaloids:

Dimethylphenylpiperazinium(DMPP)

ReversibleTertiary amines

PhysostigmineQuaternary Ammonium compounds

NeostigminePyridostigmineDistigmineAmbenoniumDemecariumTacrine

Miscelloneous DonepezilGalantamineRivastigmine

Irreversible Anticholinesterases(Organophosphorus Compounds)

Ecothiophate2) War Gases:

SarinTuban,Soman

3) Insecticides:-ParathionMalathionDiisopropyl Flurophosphate (DFP)Tetramethyl Pyrophosphate (TMPP)Octamethyl Pyrophosphotetra amide (OMPA)

Central Nervous System (CNS) - Brain and spinalcord

Peripheral Nervous System (PNS) - Located outsidethe brain & spinal cord Autonomic NervousSystem (ANS) & the somatic

The PNS receives stimuli from the CNS & initiatesresponses to the stimuli after it’s interpreted by thebrain

HEMICHOLIUM

VESAMICOL

BOTULINUM

Sites of Cholinergic Activity-Preganglionic synapses of both sympathetic and parasympathetic ganglia

- Parasympathetic postganglionic neuroeffector junctions

- All somatic motor end plates on skeletal muscles

M2 M4 M5M3M1

Gi Go

Adenylyl cyclasecAMP

Hyperpolarization (heart)Cardiac inhibitionAntagonism of smoothmuscle relaxation

RECEPTOR

INTRACELLULARTRANSDUCER

ELECTRICALMECHANICALPHYSIOLOGICALRESPONSES

Gq

Phospholipase CDiacyl-glycerol IP3

DepolarizationSmooth muscle contractionGlandular secretion

Eyes: contraction of ciliary muscle and smooth muscle of the irissphincter (miosis) – aqueous humor outflow, drainage of theanterior chamber

Cardiovascular: Bradycardia (possibly preceded by tachycardia),vasodilation (all vascular beds including pulmonary andcoronary – M3) and hypotension, reduction of thecontraction strength (atrial and ventricular cells) diastolicdepolarization ,

Negative chronotropic effect (inhibition of adrenergic activation)Negetive ionotropic effect-activation of SA node M2 receptor

GI - increases in tone, amplitude of contractions, andperistaltic activity of the stomach and intestines,enhances secretory activity of the gastrointestinal tract.

Urinary bladder - increase ureteral peristalsis, contract thedetrusor muscle of the urinary bladder, increase themaximal voluntary voiding pressure, and decrease thecapacity of the bladder.

Respiratory system-brochoconstriction and increasedbronchial secretions

Other effects – Increased secretion from all glands thatreceive parasympathetic innervation (salivary, lacrimal,tracheobronchial, digestive and exocrine sweat glands)

CNS-there are complex stimulatory effects-ataxia,behavioral disturbances and restlessness with tremorsand convulsionsBlood vessels-arteries have M3 receptors but noinnervationexagenous cholinomimetic transientbut marked fall in blood pressuredue tovasodilationendothelium release EDRF-EndotheliumDerived Relaxing Factors-NO

Other effects – Increased secretion from all glands thatreceive parasympathetic innervation (salivary, lacrimal,tracheobronchial, digestive and exocrine sweat glands)

Homotropic receptor interaction Heterotropic receptor interaction

Is the neurotransmitter of the parasympathetic N.S andcholinergic nerves, it is therapeutically of no importancedue to:1. Multiplicity of actions.2. Rapid inactivation by acetyl-cholinesterase.3. Has both muscarinic and nicotinic activity.

Structurally related to ACH, has strong muscarinicactivity but no nicotinic actions.It directly stimulates muscarinic receptors of the GITcausing increase intestinal motility and tone,It also stimulates detrusor muscle of the bladdercausing urine expulsion.Clinical uses: Atonic bladder stimulation such as inpostpartum and post operative non obstructiveurine retention.Side effects: Sweating, salivation, flushing,hypotension, nausea, abdominal pain, diarrhea, andbronchospasm.

Has both muscarinic and nicotinic actions, hasstrong effect on CVS and GIT, it causes release ofepinephrine from adrenal medulla by its nicotinicaction, using it locally on the eye cause Miosis.

Clinical uses: Rarely used because of high potencyand long duration of action except in the eye tocause Miosis and to decrease intraocular pressure.

Mainly used in ophthalmology, it exhibit muscarinicactivity, it produces rapid miosis and contraction of theciliary muscle.Clinical uses; It is the drug of choice in the emergencylowering of inrtra-ocular pressure in case of glaucoma.Side effects:It can enter the brain and cause CNS disturbances, itstimulate profuse sweating and salivation.painful spasm of accommodation for near vision.

- sol. 1%, 2%, 4%- in open angle glаucomaApplied to the eye, itpenetrates cornea andpromptly causesmiosis, ciliary muscle contra-ction, and fall in intraocculartension (< 22 mm) lasting 4-8 h.Systemic effects:sweating, salivationCardiovascular effects: in small doses – fall in BP, but in highdoses elicits rise in BP and tachycardia, probably due toganglionic stimulation (through muscarinic receptors

50

100

150

200A B C D1 min

M- и N-effects of AChBl

ood p

ress

ure[

mm H

g]

ACh2 mcg i.v.

ACh50 mcg

ACh50 mcg

ACh5 mg

M-effect

M-effect

N-effect

Atropine2 mg i.v.