Adrenergic and Cholinergic Receptors Flashcards
What are adrenergic receptors?
G-protein coupled receptors that bind adrenaline and noradrenaline, mediating the sympathetic nervous system
What are cholinergic receptors?
Ligand-gated ion channels or G-protein coupled receptors that bind acetylcholine
What are Muscarinic receptors and where do they function?
G-protein coupled receptors (cholinergic) that function in the CNS and PNS, as part of the parasympathetic nervous system.
What are Nicotinic receptors and where do they function?
Ionotropic ligand-gated ion channels (cholinergic) that function in the CNS (post-synaptic autonomic ganglia) and post-synaptic neuromuscular junctions, as part of the sympathetic and somatic nervous systems.
What are alpha1 adrenergic receptors?
Found in vascular smooth muscle cells, they mediate intracellular calcium concentration and muscle contraction
What are alpha2 adrenergic receptors?
Found in presynaptic neurons, they mediate calcium ion concentration and secretion of noradrenaline
What are beta1 adrenergic receptors?
Found in cardiac muscle, they mediate heartrate and force
What are beta2 adrenergic receptors?
Found in airway smooth muscle cells, mediate dilation
What are beta3 adrenergic receptors?
Found in adipose tissue, they mediate lipolysis
Describe a general adrenergic receptor agonist
Used for cardiac arrest or anaphylactic reactions, or taken with local anaesthetic to prolong activity. This is because adrenaline has a short duration of action and is non-selective
Describe an alpha1 antagonist
Used for treating hypertension
Describe an alpha1 agonist
Used for treating nasal congestion and hypotension. Most of these drugs have a lack of the para OH group to prevent beta activity, and a smaller substituent on the amine which allows binding in alpha receptors
Describe an alpha2 agonist
Act centrally (CNS) to decrease sympathetic flow of adrenaline and noradrenaline from the brain, treating hypertension
Describe a beta1 agonist
Used for cardiac shock treatment, short acting as it is easily metabolised due to catechol ring and phenol, the large R group makes it beta-selective, and the extra OH group in the phenol causes hydrogen bonding with the extra polar binding region
Describe a beta2 agonist
SABAs: e.g. salbutamol, used to treat asthma attacks. Drugs can be non-selective or beta- or beta2-selective
LABAs: hydrocarbon substituent causes it to be longer acting
Describe a beta1 antagonist
Beta blockers, used to treat angina and hypertension
What are direct, indirect and mixed acting drugs?
Direct - Drugs that target the receptor
Indirect - drugs that regulate neurotransmitter release, synthesis, breakdown, uptake or storage
Mixed - act directly and indirectly
Give an example of a mixed acting drug
Ephedrine and psuedoephedrine directly activate alpha and beta receptors, and indirectly act by inhibiting noradrenaline reuptake and increasing noradrenaline release from vesicles in nerve cells
What is acetylcholine and what makes acetylcholine a flexible molecule?
Acetylcholine is a excitatory neurotransmitter, which excites nerve cells to carry a signal.
It can adopt different conformations allowing it to bind to both muscarinic and nicotinic receptors
What do muscarinic antagonists do?
Cause increased heart rate, relaxation of smooth muscles, inhibition of gastric acid and saliva secretion
Describe drugs that act on nicotinic receptors
depolarising blockers - agonist, produces initial contraction of muscle fibres. Prevents end-plate potential from producing a propagated action potential by maintaining depolarisation
Non-depolarising blocker - competitive antagonist, competes against acetylcholine to block transmission
What does Anticholinesterase do?
inhibits acetylcholinesterases to slow/prevent degradation of acetylcholine released at synapses.
Short acting - bind to anionic site of cholinesterase, blocking cholinesterase binding
Medium acting - interact with the serine hydroxyl of esteractic site, produces carbamylated enzymes which are hydroxylated slower
Long acting - irreversibly phosphorylates serin hydroxyl group of esteractic site, changing the conformation of the binding site. this takes days to regenerate
Describe Cholinesterase and what it does
Serine hydrolases that catalyse hydrolysis of acetylcholine into choline and acetic acid, the active centre of cholinesterase has 2 areas (anionic and esteractic sites) that both interact with acetyl choline
What is the neurotransmission process of noradrenaline?
NA is synthesised in presynaptic neuron and stored.
Activation signal causes fusion of the vesicles and releases NA into the synaptic cleft.
NA binds to receptor on postsynaptic neuron, causing a new signal.
NA departs from receptor back to the presynaptic neuron.
NA is reabsorbed by active transport into the presynaptic neuron and repackaged or metabolised.
This process is inhibited by:
Self-inhibition, high conc of noradrenaline at presynaptic alpha2 receptors.
Prostaglandin acting on prostaglandinE2 receptors.
Acetylcholine acting on presynaptic muscarinic receptors.
Describe the levels of the Peripheral nervous system
Efferent neurons – carry signals away from CNS
- Automatic nervous system – controls involuntary bodily functions
- [Parasympathetic/cholinergic system (rest-and-digest, Acetylcholine)]
- [Sympathetic/Adrenergic system (fight-or-flight, adrenaline/noradrenaline)]
- [Enteric (gut) system]
- Somatic nervous system – controls skeletal muscle movement
Afferent neurons – carry signals towards CNS
Describe the structure-activity relationship for adrenergic drugs
The para and meta OH phenol substituents are both important, involved in H-bonding especially to beta-receptors. Lack of the para OH leads to alpha1 selectivity.
Primary and secondary amine groups have good adrenergic activity (ionic bonding to receptor), whereas tertiary amines and ammonium salts do not.
Noradrenaline is more alpha than beta selective. Replacing the nitro group with a bulky alkyl group (e.g. isopropyl) makes it a selective beta agonist, as the molecule cannot fit into the alpha-adrenoceptor, and creates new hydrophobic binding in beta receptors.
The aromatic ring is involved in van der Waals interactions. the R-Enantiomer is more active than the S-Enantiomer.
Describe the structure-activity relationship for cholinergic drugs
The general structure of cholinergic drugs includes the acetoxy group, the ethylene bridge and the quaternary amino group.
The acetoxy group - An acetyl group is more active that larger groups, and more susceptible to hydrolysis by cholinesterases, than carbomate esters.
Ethylene bridge - increasing the length of the carbon chain decreases the activity. Replacing a hydrogen atom with a methyl group increases cholinergic activity, but larger groups decrease activity.
quaternary amino group - Important for muscarinic activity. Compounds containing 1°/2°/3° amino groups are less active. Replacing the methyl group with larger alkyl groups creates an inactive compound.
