Introduction:
- Autonomic nervous system is
a part of nervous system that controls and regulates the internal
organs/body.
- It control involuntary
response , e.g. Breathing, digestion.
- Two type:-
1. Sympathetic
: >When our body is in abnormal situation it works(fight or
flight situation). >Work such as increase heart rate, decrease digestion rate.
2. Parasympathetic:> When our body come back from sympathetic nervous system to normal condition. >Works such as normal heart rate & digetion rate
Adrenergic Neurotransmitters:
Adrenergic:
Adrenergic drugs are the agents which acts directly on the sympathetic
nervous system and these drugs are also known as sympathomimetic drugs as these
agents mimics(copy) the actions of sympathetic nervous system.
Neurotransmitters:
Neuro: Neuron ;
transmitter: transfer the
information
Neurotransmitter are chemical messenger that
transmit signals from a neuron to a target cell/neurons across a synapse.
- Sympathetic is called Adrenergic.
- Parasympathetic is called
Cholinergic.
- Both Adrenergic and Cholinergic
division work antagonistically.
- Dopamine: it is a naturally occurring catecholamine it acts as a neurotransmitter in the basal ganglia of CNS.
- Epinephrine: It produce in stressful situation,
increase heart rate & blood flow.
Leading to physical boost &
heightened awareness.
It is also named as Adrenaline.
- Norepinephrine: It affect attention and responding
action in the brain.
Contract blood vessels, increasing blood
flow.
Biosynthesis and catabolism of catecholamine
Catecholamines: It is a mono amino neurotransmitter, in which catechol ring is present with a side chain amine
Biosynthesis of catecholamine:
The biosynthesis take place in
adrenergic and dopaminergic neurons in the CNS, in sympathetic neurons in the
ANS and in the adrenal medulla.
1. Phenylalanine
get hydrolyzed into tyrosine in liver.
2. Tyrosine get
hydrolyzed into DOPA by the enzyme tyrosine hydroxylase, in cytoplasm.
3. DOPA
converted into Dopamine with the help of enzyme DOPA decarboxylase in
which CO2 removed, in cytoplasm of neurons, forms
Dopamine(first catecholamine formed).
4. Dopamine
is converted into nor-adrenaline with the help of enzyme dopamine β-hydroxylase,
nor-epinephrine formed.
5. Nor-adrenaline
get converted into adrenaline with the help of enzyme Pheylethanolamine-N
methyl transferase (PNMT), in the adrenaline medulla.
Catabolism of catecholamine
> It is the removal of Catecholamines and also termination of action of
catecholamine.
Enzymes:
1. MAO: Monoamine
oxidase(deamination)
2. COMT: Catechol
o-Methyl transferase(methylation in ring)
Adrenergic receptors and their distribution :
Adrenergic receptor:
Adrenergic receptor are
those receptor in which adrenergic drugs/neurotransmitter will bind directly to
increase various action/response.
- Adrenergic receptor are membrane
bound G-protein coupled receptors.
- these are classified into two
types:
> α
receptors: -α1, α2
> β receptors
:- β1, β2, β3
Distribution of adrenergic receptor with their action:
1. α1 receptors: > Present on post synaptic receptor sites. > Smooth muscles of blood vessels (vasoconstriction). Function: > Gland cells (Gland secretion). > Glycogenolysis in liver (glucose synthesis). > also present in iris, bladder, uterus etc. -these are mainly excitatory in nature.
2. α2 receptors : > Present on pre and post-synaptic receptor sites. > Presents in CNS, Pancreas Function:> inhibit neurotransmitter release. > Decrease insulin release. > Platelet aggregation. - these are mainly inhibitory in nature.
3. β1 receptors : > Present in cardiac tissue (myocardium) i.e. Heart and in Kidney. Function:> contraction and heart rate increases. > Release Renin from Kidney results increase B.P. - Excitatory in nature.
4. β2 receptors : > Present in smooth muscles and gland cells, i.e. Bronchi, Blood vessels, Veins, Liver, G.I.T. Function:> Relaxation- Bronchodilator, Vasodilatation, Vein relaxation. -inhibitory in nature.
5. β3 receptors : >Present in adipose tissue
and urinary bladder.
Function:>Lipolysis,
relaxation.
Sympathomimetic Agents: SAR of Sympathomimetic agents:
Sympathomimetic agents:
-Also known as adrenergic agonist.
-Sympathomimetic - Sympatho- sympathetic nervous system
mimetic- mimic (copy)
- Sympathomimetic agent are those
chemical agents/drugs which copy the action of sympathetic nervous
system.
- These agents/drugs bind with
adrenergic receptor and give action.(act as adrenergic neurotransmitter.
SAR of Sympathomimetic
agents:
SAR:-Structure
activity relationship
- It is defined as the relationship
between the chemical structure of a molecules and its biological
activity.
- This allows modification of the
effect or potency of a substance b changing its chemical structure.
Sympathomimetic agents:-
Structurally, Substitution is possible on :-
- Catechol(aromatic ring)
- β-carbon
- α-carbon
- Amino group
- Presence of -OH group at alternate
(3,4 position) gives maximum α,β activity, Absence of
these group decrease α,β activity(also their
potency)
- But unsubstituted(without
-oh group) aromatic ring, easily cross blood brain barrier (BBB)
and have more CNS
-OH group attachment
on carbon decrease CNS activity due to lower to lower liquid solubility
Of the drug .But increase the α activity
e.g.:- Ephedrine
Drugs having substitution
on carbon block the metabolism (activity of MAO) larger duration of
action
e.g.:- Amphetamine
The amino
group is essential (primary or secondary), but tertiary are poor direct
agonists
1° and 2° amino
group-high α selectivity (activity) e.g.:- adrenaline
More the size of alkyl substituent, higher will be β selective
action and lower α selectivity.
e.g.:-
Isoprenaline, salbutamol.
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