Adrenergic

Question 1

1930

Answer 1

Z.M Bacq
Yohimbine Paradox
Took nicotsating membrane of cats eyes made of smooth muscle
At this point thought adnreline was the sympathetic neurotransmitter
Injected adrenaline and added yohimbine (knew it was a vasodilator) and found contraction was blocked - expect as adrenaline causes constriction and yohibine would reverse this
Then stimulated the nerve and found yohimbine didnt block the contraction

Question 2

1946

Answer 2

Von Euler

Discovered that it was noradrenaline not adrenaline in the sympathetic nervous system

Question 3

1948

Answer 3

Alquist
Took noradrenaline, adrenaline and isoprenaline and added them to the vas deferens and the heart
Found that in the vas deferens the potency order went NA > A > iso (called this the alpha tissues
and in the heart the potency order went Iso > A > Na (called this the beta tissues)

Question 4

1957

Answer 4

Brown and Gillespie
In a cat again
found when they used phenoxybenzamine (an alpha blocker) and stimulated the spenic nerve there was a huge increase in NA release from the vein - thought this was because the neurotransmitter was being used up by the receptors which is wrong - in 1960 it becomes clear than PBZ is an adrenoceptor antagonist and also blocks uptake 1 and uptake 2 mechanisms but even when all these are blocked with PBZ still potentiates neurotransmitter output so it must have another effect

Question 5

1974

Answer 5

Starke and Langer
Solve the yohimbine paradox
Take an uptake 1 antagonist, an uptake 2 antagonist and yohimbine and you get the effect of PBZ (increased transmitter output) - yohimbine must be blocking a PREJUNCTIONAL ALPHA RECEPTOR that leads to transmitter output - called this a2 and the original post junctional one alpha 1

Question 6

1980

Answer 6

Doherty and McGrath
Used xylazine (alpha 2 agonist) and phenylephrine (alpha 1 agonist) and found prazoin blocks phenylephrine response but yohimbne blocked both - since the prejunctional a2 would not be in action since there is no nerve stimulation but mean yohimbine is blocking the post junctional alpha 2

Question 7

1980-2

Answer 7

McGrath gone solo
Took phenylethanolamines (alpha 1 agonist like phenylephrine and noradrenaline) and imidazolines (alpha 3 agonists like xylazine) and showed that some the alpha adrenoceptor could be further subdivided into alpha1a and alpha1b based on the sensitivity to alpha2 drugs

Question 8

1986

Answer 8

Bylund
Took radioactive yohimbine (an alpha 1 and 2 antagonist) and prazosin (an alpha 1 antagonist) and found that in some cases the prazosin competed off the yohimbine which you would not expect - can now classify the alpha 2 adreoceptors into a2a = e.g. low affinity for prazosin and a2b high affinity for prasozin e.g. in the brain

Question 9

1967

Answer 9

Lands conducted a study like alquist and found that different tissues have different responses to sympathomimetics so subdivded the b receptors e.g. b2 in the lungs and b1 in the heart and fat

Question 10

Yohimbine

Answer 10

Alpha 1 and alpha 2 antagonist used in 1930 by Z.M bacq which lead to the yohimbine paradox, 1974 by starke and langer when they found it was an alpha 2 blocker and solved the yohimbine paradox

Question 11

Phenoxybenzamine

Answer 11

Alpha 1 and 2 adrenoceptor antagonist, uptake 1 and 2 blocker used

Question 12

Xylazine

Answer 12

An imidazolines alpha 2 agonist

Question 13

Phenylephrine

Answer 13

A phenylethanolamine alpha 1 agonist

Question 14

Prasozin

Answer 14

Alpha 1 antagonist

Question 15

Cocaine

Answer 15

Uptake 1 blocker

Question 16

Rauwolfia serpentina

Answer 16

Contains the ingredients resperpine, yohimbine, raulwolscine and corynanthine

Question 17

Raulwolscience

Answer 17

Stereoisomer of corynanthine

alpha 2 receptor blocker

Question 18

Corynanthine

Answer 18

Stereoisomer of raulwolscience
Alpha 1 receptor blocker
R

Question 19

Resperpine

Answer 19

Blocks the vesicular monoamine transpoter located on the vesicle that allows uptake of dopamine into the vesicle where it is converted to NA by DOPa b-hydroxylase so leads to a build up of dopamine and no NA
Reserpine also blocks the uptake 1

Question 20

Disulpfram

Answer 20

Blocks dopadecarboxylase which onverts dopa to dopamine

Question 21

Tetrodotoxin

Answer 21

Block sodium channels and inhibits nerve depolarisation and NA release

Question 22

Hexamethoium

Answer 22

A non-depolarising ganglion blocker that blocks acetylcholine at autonomic ganglia and therefore prevents AP firing to release NA

Question 23

a-methyltyrosine

Answer 23

Blocks tyrosine hydroxylase which converts tyrosine to DOPA

Question 24

Tyrmaine, amphetamine

Answer 24

Get into the varacosity via the uptake 1 and displace NA from the vesicles - this causes release of NA via the NET

Question 25

Guanethidine

Answer 25

gets in via the uptake 1 and displaces NA from the vesicles which causes an initial contract but then damages the varacosity leading to eventual relaxation

Question 26

Caridopa

Answer 26

Blocks dopadecarboxylase which breaks down levadopa used to treat parkinsons so carpidopa is used as an adjunct in parksinons treatment

Question 27

Methyldopa

Answer 27

Taken up into the nerve terminal where it acts asa false adrenergic transmitter and is released and acts on the alpha 2 receptors decreasing the release of NA without itself having any of the other actions of NA