PH2113 - Neuropharmacology 4 Flashcards
What is the structure of the ionotropic receptor?
Membrane pore 4 transmembrane spanning helices Channel made up of 5 subunits M2 subunit lines the pore Charged amino acids at the top and bottom create the selectivity A ring of leucines for the 'gate' - closed in the absence of a ligand - determine the pore size - determines the size of the ion that passes through
What can ligand-gated ion channels be affected by?
Agonists - ligand Antagonists Channel blockers Allosteric modulators
What are the features of nicotinic acetylcholine and 5-HT3 receptors?
Na+/K+
Stimulatory
What are the features of GABA receptors?
Cl-
Inhibitory
What are the current or potential therapeutic applications of acetylcholine receptor active compounds?
Tobacco addiction - varenicline/bupropion General anaesthetics Alzheimer's disease Parkinson's disease Schizophrenia ADHD Neuropathic pain
Give examples of therapeutic applications of 5-HT3 receptor modulators
Agonists may alter mood - varenicline - lamotrigine maybe inverse agonist Antagonists - nausea and vomiting - chemotherapy - radiotherapy - post-surgical - post-operative neuropathic pain - headache and migraine
What is the structure of the GABA receptor?
5 subunits
- 2 alpha
- 2 beta
- 1 gamma
What are the two types of L-glutamate receptor?
NMDA receptor
non-MDA receptor
- AMPA
- kainate
What is the function of the AMPA glutamate and kainate receptor?
Fast synaptic excitation
Which diseases can be caused by faulty NMDA receptors?
Alzheimer's Parkinson's Huntington's Schizophrenia Epilepsy Encephalitis Stroke
Give an example of an agonist for an NMDA receptor
Glutamate
Aspartate
NMDA
Give an example of an antagonist for an NMDA receptor
D-AP5
What effect does having variable subunits have on a receptor structure?
Diversity of channels Different ligand binding affinities - AMPA vs kainate Differential expression in specific regions Developmental changes - nACh Differential permeability to ions - AMPA vs kainate Greater opening of the channel - AMPA receptor
What effect does having different types of pharmacological regulators have?
Direct binding - competitive agonists/antagonists Indirect binding - non-competitive agonists/antagonists Ion channel blockers Allosteric modulation
What is a metabotropic receptor?
G-protein coupled receptor
What is the function of a metabotropic receptor?
Mediate cellular response to neurotransmitters or hormones
Directly responsible for senses of sight, smell and taste
What are the two classes of metabotropic receptors?
Rhodopsin-like 7-transmembrane segment
Secretin receptors
What are the properties of rhodopsin-like 7-transmembrane segment receptors?
Largest group - > 300 Family 1 - family A Receptors for more transmitters Short extracellular N terminal
What are the properties of secretin receptors?
Approximately 34 Family 2 - family B Receptors for peptide hormones Ligand binding on intermediate extracellular tail
All have a hormone binding domain and bind peptide hormones
What is rhodopsin?
Photopigment in rods
Give four examples of hormones used to target secretin receptors?
Calcitonin - hypercalcaemia Glucagon - hypoglycaemia GLP-1a - glucose regulation Parathyroid hormone - osteoporosis
