PHA3011 Lecture Notes - Lecture 1: Decongestant, Adrenergic, Sympathomimetic Drug
Lecture 2 Principles of neurotransmission
and the ANS
There are subtypes of adrenoceptors. The
first studies examined the effects of known
adrenergic agents of blood pressure.
This lead to the idea of alpha and beta
receptors. Based on their relative potencies.
NA at α1 ; Adr at α1 or β2 ; Iso at β2. These
catecholamines are released endogenously.
They all work at the same types pf receptors
have different types of effects.
• α1 AR ↑ IP3; ↑DAG
• α2 AR ↓cAMP
• β AR ↑ cAMP
In general alpha is associated with contraction
(alpha2 can be autoinhibitory though) and
beta is associated with relaxation.
Subtypes may co-exist and the response of a
tissue depends on the predominant subtype
of receptor activated, the relative populations
in the tissue, relative potency of the agonist
(NA vs Adr). Effects at a receptor depend on
the affinity for, and efficacy at,
adrenoceptors; interaction with removal
systems (eg uptake; MAO; COMT).
α-AR: NA ≥ Adr > Iso
β-AR: Iso > Adr ≥ NA
In the SM of blood vessels alpha1 and 2 are
present under the nerves (both have a similar
effect). The beta2 are present but are affected
by circulating adrenaline rather than the
nerve terminal release of NA.
Direct vs indirect activation of adrenoceptors
Indirectly acting sympathomimetics don’t act
directly at the receptor themselves they act
via:
• Enter the nerve terminal via uptake 1
(compete with NA)
• Taken up into vesicles in exchange for
NA
• Released NA escaped via uptake 1 or
broken down
The effects are similar to NA/ stimulation of
sympathetic nerves. Eg ampthetamine;
ephedrine/ pseudoephridrine; tyramine.
Indirectly acting sympathomimetics can be
used therapeutically as a nasal decongestant.
pseudoephedrine/ ephedrine acts at the
alpha1AR to decrease mucous production.
Note that we will not see the effect of an
indirectly acting sympathomimetic where
there are no nerves (will not see
bronchodilation ect). They only work were the
sympathetic nerves are.
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Autoinhibition occurs on the presynaptic
nerve terminal via alpha2 receptors which NA
bind to.
Document Summary
Ar: iso > adr na and the ans. The first studies examined the effects of known adrenergic agents of blood pressure. In the sm of blood vessels alpha1 and 2 are present under the nerves (both have a similar effect). The beta2 are present but are affected by circulating adrenaline rather than the nerve terminal release of na. This lead to the idea of alpha and beta receptors. Na at 1 ; adr at 1 or 2 ; iso at 2. They all work at the same types pf receptors. Have different types of effects: 1 ar ip3; dag, 2 ar camp, ar camp. In general alpha is associated with contraction (alpha2 can be autoinhibitory though) and beta is associated with relaxation. Subtypes may co-exist and the response of a tissue depends on the predominant subtype of receptor activated, the relative populations in the tissue, relative potency of the agonist (na vs adr).
