12 Properties of Drug Targets and their Biological Processes Flashcards
Drug target definition
molecules usually proteins, which play a pivotal role in existing physiological or biochemical process, the function of which can be modulated by a drug to produce a biological effect
Drug target examples
receptors / ion channels / transporters / enzymes
What are ion channels formed of
3-5 subunits
Regulation of ions
Ligands bind to an extracellular domain. Part of each subunit (pore domain) forms a hydrophilic (water filled) channel to selectively allow ions to flow through the membrane
2 types of ion gated channels
Ligand gated ion channel receptors
Voltage gated ion channels
Voltage gated ion channel process description
Action potential
Voltage gated Ca2+ channel open
Synaptic vesicles + Ach diffuse across the synapse
Nicotine Ach receptor (ligand gated ion channel is open)
Na+ influx, depolarisation and muscle contraction
Ion channel blcokers
Permeation blocked
Ion channel modulators
Increased or decreased opening probability
Voltage gated calcium channel blockers physiology
Ca2+ currents drive signalling in vascular smooth muscle cells and some cardiac cells
Voltage gated calcium channel blockers Pharmacology
Ca2+ channel blockers are used to treat cardiac disorders
Ion channel blocker example
- Muscarinic M3 acetylcholine G protein coupled receptor signalling
- Contraction of vascular smooth muscle
- Ca2+ channel blockers
- Treatment for Hypertension
- Lowers risk of cardiovascular events resulting from vascular damage
G-protein coupled receptors - what are they
Single protein polypeptide
7 transmembrane domains (alpha helices)
G protein is a guanine nucleotide binding protein made of 3 subunits (alpha, beta, gamma)
What do ligands bind to on g-protein coupled receptors
extracellular domain or within transmembrane domain (depending on type)
What happens upon ligand binding with g-protein coupled receptors
The alpha subunit binds GTP and dissociates (to GDP) from the complex
A subunit is then free to activate target ion channel or enzyme
What have endogenous chemical molecules evolved to do
fine-tune the control of cells and physiological functions
(eg. Neurotransmitters and hormones / stimulate and inhibit (mood) / contract and relax (muscle) / reduce and increase (heart beat)
Time - rapid (seconds)
Transporters / carriers use
Transporters move ions and chemicals against their electrochemical (concentration/voltage) gradient
This requires energy provided by ATP hydrolysis “active transport”
Primary active transport
Direct
Secondary active transport
Co-transport
Doesn’t require a chemical source of energy such as ATP, uses an electrochemical gradient generated by primary active transport. Ion is then transported back together with an additional molecule
Example - antidepressant transport
Drug - Fluoxetine (SSRI)
Block the reuptake of serotonin (5HT) back into the presynaptic neuron and recycling into vesicles, increase the exposure time od serotonin (5HT) in the synaptic cleft. Prolongsthe activation of serotonin receptors in different regions of the brain
Improve mood, emotion and sleep
What do enzymes catalyse
Enzymes catalyse the conversion of a substrate into a produce
Most drugs acting at enzymes are…
Inhibitors
What can drugs do (2)
Drugs can also potentiate enzymes (eg. Increase their activity)
Drugs can be converted from their inactive form to their active form
Example - Anticholinesterases and anaesthesia (drugs acting on receptors)
Nicotine acetylcholine receptor signalling
Drug - Neostigmine
Block the enzymatic clearance of Ach, increase the exposure time of Ach in the synaptic cleft, prolongs the activation of nicotine Ach receptors, reverses muscle relaxation
