Neuropharmacology Flashcards
Define drug
Chemical applied to a physiological system that affects it function in a specific way
Outline ligand
Any molecule or atom which binds reversibly to a protein
Define agonist
Drugs which ‘activate’ receptors
Define antagonist
A drug that binds to the receptor without causing activation, and therefore block the effect of agonists on that receptor
Outline reversible antagonist
Compete with agonist binding typically at the same site. Binds reversibly
Define irreversible (covalent) antagonist
Binds irreversibly to receptor. May change the conformation of the receptor to reduce ability of agonist to bind
Define affinity
How well a drug binds to its receptor
Define efficacy
How well a drug once bound to a receptor elicits a response
Define potency
A measure of the amount of drug required to elicit a response of a given intensity
Define orthosteric site
The primary ligand binding site of a receptor
Define Allosteric site
A site distinct from the endogenous ligand
Define neurotransmitters
Biochemical that mediates fast-acting direct communication between two neurons (pre-and post-synaptic)
Define neuromodulaters
Biochemical that modulates activity of neurons and neural networks by changing the ability of neurons to response to neurotransmitters. Can act locally or at sites remote from where they are synthesised
What is occupation (binding) governed by in the two-state model
Affinity - how well the drug binds to the receptor
What is activation governed by in the two-state model
Efficacy- how well a drug bound to a receptor elicits a response
Outline the Neuro modulator nitric oxide
-Ca2 influx into cells downstream of ion-channel opening leads to activation of neuronal nitric oxide synthase which increases intracellular nitric oxide levels
NO activates cGMP and MAPK signalling which modulates function of the postsynaptic neuron
NO can also diffuse retrogradely and impact neurotransmitter release from the presynpatic neurons
What transmitters can glial cells release which modulate neuronal activity
Glutamate
ATP
Adenosine
D-serine
Cytokines
Neuropeptides
Eicosanoids
Outline ionotropic receptors
Activated by binding of neurotransmitters
Channel opening
Ions flow into postsynaptic cell
What is the structure of ligand-gated ion channels
-typically heteromeric assemblies of 4 or 5 subunits
-each subunit has transmembrane spanning helices which when assembled for a central aqueous channel
Outline metabotropic receptors
-not directly coupled tp ion channels
-can regulate ion channel opening
What is the timescale of ligand gated ion channels
Milliseconds
What is the timescale of G protein coupled receptors
Seconds
What is the timescale of kinase linked receptors
Hours
What is the timescale of nuclear receptors
Hours
Outline G-protein coupled receptors
Metabotropic receptors
-ligand binding induces GDP to GTP exchange on the Ga subunit
-Ga subunit dissociates from By complex
-Ga subunit and By complex activate downstream targets
-when bound to target GTPase activity of Ga subunit is increased leading to hydrolysis of GTP to GDP
Outline kinase linked receptors
-ligand binding leads to dimerisation of receptors
-receptor diners undergo auto-phosphorylation at tyrosine residues
-pTyr sites recruit proteins with SH2 domains leading to activation of downstream signalling
