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Adrenergicdrugs PDF
Adrenergicdrugs PDF
CNS PNS
Autonomic Somatic
Preganglionic -
Nerve fibre Myelinated myelinated
Post ganglionic – non
myelinated
Peripheral plexus Absent Present
Formation
Vagusstuff of Dale
9 It should be present in the presynaptic neurons
9 It should be released following the nerve stimulation
9 Its application produces responses similar to those produced
by nerve stimulation
9 Its effect should be blocked or potentiated by the substance
which similarly alter the effect of nerve stimulation
STEPS IN NEUROHUMORAL TRANSMISSION
Impulse conduction
Transmitter release
Action on the postjunctional membrane
Postjunctional activity
Termination of transmitter action
????
Adrenaline
Adrenergic System & Drugs
Dr Satyajit
Catecholamines ????
“Catechol”
1,2 dihydroxybenzene
Most abundant endogenous
catecholamines
9 Adrenaline / Epinephrine
9 Noradrenaline / Norepinephrine
9 Dopamine
Adrenaline Dopamine
Noradrenaline
Noradrenaline
post ganglionic sympathetic sites (sweat glands,
hair follicles)
Adrenaline
Adrenal medulla, transmitter in brain
Dopamine
Major transmitter in basal ganglia, limbic system,
CTZ, anterior pituitary
Synthesis of catecholamines
Phenylalanine
Hydroxylase Liver
Tyrosine
Hydroxylase
DOPA Adrenal neuronal cytoplasm
Decarboxylase
Dopamine
ß Hydroxylase Inside granules
Noradrenaline
Methyl transferase Adrenal medulla cells
Adrenaline
Synthesis of NA/NE occurs in ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐???
Adrenaline occurs only in ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐??
Storage of catecholamines
Noradrenaline
Synaptic vesicles within adrenergic nerve endings
Vesicular membrane actively takes DA
Dopa decarboxylase
NA forms a complex with ATP (4:1)
Adsobed to chromagranin
Adrenaline
In adrenal medulla, NA is diffused to cytoplasm
Methylation – N‐methyl transferase
NA ‐‐‐‐‐‐‐> Adrenaline
Release of catecholamines
Release of CA occur by exocytosis
All components (NA, Adr, ATP,dopamine hydroxylase)
Co transmitters
Indirectly acting sympathomimetic ???
9 Displace NA from nerve binding site
9 Exchange diffusion by NET
Uptake of catecholamines
Axonal Uptake
9 Uptake 1
9 Active amine pump (NET)
9 Transports NA by Na+ coupled mechanism
9 Takes NA more than Adr
9 Most important in terminating action of NA
9 Inhibited by Cocaine, desipramine
Vesicular uptake
VMAT‐2 (vesicular monoamine transporter)
Transports NA from cytoplasm to vesicles
Exchange with H+ ion
Takes dopamine for synthesis of NA
Maintain the conc of NA
Inhibited by reserpine
Uptake 2
9 Extra neuronal uptake
9 No pharmacological importance
Metabolism of catecholamines
DOPGAL : 3,4 dihydroxyphenylglycolaldehyde
DOPEG: 3,4 dihydroxy phenylethylene glycol
DOMA: 3,4 dihydroxy mandelic acid
MOPEG : 3 methoxy 4 hydroxy phenylethyleneglycol
Excretion
9 Metabolites excreted in urine is VMA, MOPEG,
DOMA
9 Mostly conjugated with glucuronic acid or sulfate
before excretion
9 Only 2‐5 mic gm of Adr and 25‐50 mic of NA excreted
in free form in 24 hrs
Adrenergic receptors
Raymond Ahlquist , 1948
Types of Adreno receptors
2 types
¾ α receptors
¾ ß receptors
9 Membrane bound GPCR
9 Increase or decrease the cAMP or IP3 /DAG
¾ ß1
¾ ß2
¾ ß3
Beta receptor – ß1
Heart
JG cells of kidney
Agonist‐ Dobutamine
Selectivity : Adr = NA
ß1
↑Cardiac stimulation, ↑rate, force and conduction
Beta receptor – ß2
Smooth muscle : bronchus
GU, Intestine
Uterus
Urinary tract
Eye
Agonist : salbutamol, terbutaline
Selectivity : Adr > NA
ß2 ß2
↑Bronchodilatation Relaxation
ß2
Relaxation
Beta receptor – ß3
Adipose tissue
Affinity : NA
Agonist – antiobesity drugs
Alpha receptor – α
α1
α2
α3
Vasoconstriction
GU smooth muscle ‐ contraction
Gland ‐ secretion
Gut ‐ relaxation
Agonist: Phenylephrine
Antagonist ‐ Prazosin
α1
Alpha receptor – α2
Pre junctional nerve endings (α2A)
Post junctional – Brain, pancreatic beta cells
Inhibition of transmitter release
Decrease central sympathetic outflow
Decrease insulin release
Agonist: Clonidine
Antagonist ‐ Yohimbine
Organ αAction ß action
Blood vessels Constriction (α1) Dilatation (ß2)
(arterioles and
veins)
Heart Little action Stimulation (ß1)
Catecholamine
Adrenoreceptors
Thank you