Chemistry of beta blockers Flashcards
What are the 2 types of nervous systems in the peripheral nervous system
Adrenergic (uses adrenaline and noradrenaline) and cholinergic (uses acetylcholine)
Which out of noradrenaline, adrenaline and acetylcholine are neurotransmitters and hormone
Adrenaline = hormone
Other 2 = neurotransmitter
What are the two types of adrenoceptors
There is alpha and beta GPCR adrenoceptors:
Alpha 1 = Gq receptors that produces IP3 and DAG
Alpha 2 = Gi receptor that lowers cAMP
Beta 1 = Gs receptor that activates adenylate cyclase increasing cAMP
Beta 2 = Gs receptor that activates adenylate cyclase increasing cAMP
Beta 3 = Gs receptor that activates adenylate cyclase increasing cAMP
Where are B1 receptors most likely to be found
Cardiac muscle
Where are B2 receptors most likely to be found
Bronchial smooth muscle
What are 2 agonists of b1 receptor and why
Noradrenalin and adrenaline,
The catechol ring system
What are 2 molecules that cannot bind to the b1 receptor
Tyramine and amphetamine because they lack 2 charged regions on the front of the ring
Why can isoprenaline not bind to b1 receptor but can bind to a1 receptor
The b1 receptor has a hydrophobic binding region and the dipole area on the isoprenaline prevents it from binding
What is referred to as the first lead
The part of the molecule which first binds to the binding site on the molecule
What is special about DCI (dichloroisoprenaline)
Has the same structure as adrenaline however modified catechol ring system (2 Cl- instead of OH-) however is still able to bind to the same binding site and so can act as a partial agonist ( same binding site however reduced efficacy)
What is special about pronethalol
It has the same structure as adrenaline however has a double phenol group as opposed the catechol ring structure.
Pronethalol was found to block beta receptors
What was pronethalol used for
To treat high blood pressure, cardiac arrhythmia and angina
Why did the structure of propanethalol need altering and how was it altered
It was toxic and caused tumours, thus spacers and linking groups were added. Alpha napthol ans opposed to a beta napthol ( so going upwards).
Advantages of propranolol vs propanethalol
Propranolol is 20x more effective, has a high potency and less side effects.
What are epoxides/ epichlorohydrins and what is its physical properties
A triangle shaped structure with 2 carbons and an oxygen at the top of the triangle
O / \ CH — CH
- The oxygen atom causes the 2 carbons to be electrophilic.
-the internal angle of the structure is 60º and so helps nucleophiles to bind
