LS1- Receptors and Ion Channels Flashcards
Isoprenaline
β-adrenoreceptor agonist. The D-isomer is inactive but has affinity so acts as a competitive antagonist with the L-isomer.
Acetyl-β-Methylcholine
AChR Agonist. Its isomer is inactive and has no affinity.
Nicotine
NAChR Agonist
Atropine
MAChR Antagonist
Muscarine
MAChR Agonist
D-Tubocurarine
NAChR Antagonist
Benzilylcholine
Irreversible MAChR antagonist. Causes alkylation of the receptor. Demonstrates the spare receptor principle, as maximal responses can still be achieved in the initial period after application.
Cholera Toxin
Causes ADP ribosylation of αs subunit, which inhibits it’s intrinsic GTPase activity. Results in sustained activation of adenylyl cyclase.
Pertussis Toxin
ADP ribosolation of αi prevents activation of Gi in response to receptor stimulation, therefore preventing inhibition of adenylyl cyclase activity.
Lithium
Uncompetitive inhibitor of phosphatase that converts IP1 to inositol. Blocks IP3 recycling pathway, affects the brain particularly since blood cannot provide an alternative source of IP3 as it does not cross the BBB. Used to treat manic depression.
Tyrphostins
Inhibitors of tyrosine kinases. Have potential uses if the treatment of neoplastic growth.
Prednisolone
Glucocorticoid Receptor Agonist. May have anti-inflammatory or immunosuppressive effects.
Mifepristone
Glucocorticoid R Antagonist. Also a partial progestagen R agonist. It has abortifacients effects.
Fludrocortisone
Mineralocorticoid R agonist. Used in replacement therapy to treat Addison’s disease.
Spironolactone
Mineralocorticoid R antagonist. Diuretic effects
Ethinylestradiol
Estrogen receptor agonist, used in HRT and for contraceptive purposes.
Tamoxifen
Estrogen R antagonist used in the treatment of breast cancer
Norethisterone
Progestagen receptor agonist used in contraception
Danazol
Progestagen R antagonist. Used in the treatment of endometriosis and menorrhagia. In men, it can be used to treat gynomastia
Lidocaine
V-gated Na+ channel blocker. LA. Use-dependent, so has a mild selectivity for rapidly firing pain fibres. Shifts the inactivation curve of the channel to the left, such that at any given membrane potential, a greater proportion of the channels are inactivated. It is a weak base (pKa 8-9) so exists in both forms at the physiological pH. It needs to cross the CSM in the unprotonated form, but is a more potent blocker in its charged, protonated form. It binds preferentially to the I form of the channel, so is most effects in ischaemic tissue. Used to treat ventricular dysthymia, and has fast association/dissociation properties.
Procaine
V-gated Na* channel blocker. LA. A weak base (pKa 8-9) so exists in both forms at physiological pH. Most potent in the protonated form, but needs to cross CSM unprotonated.
QX314
A quaternary LA which is a permanently charged form of lidocaine. It is inactive when applied externally, but potent when infused.
Benzocaine
V-gated Na+ channel blocker that acts as a LA. It is always uncharged (pKa 2.6) so it only enters via the hydrophobic pathway, showing no use dependence. It is not affected by pH changes in the physiological range, as shown in the Hille experiments.
Quinidine
V-gated Na+ channel blocker, LA. Slow association/dissociation properties means it shows use dependence at low rates of stimulation only. It is used to treat supraventricular tachycardia.
Tetradotoxin
Na* channel blocker. Possesses a guanidinium. Blocks the channels from the outside, showing no use dependence.
Bay K 1844
L-Type Ca2+ channel agonist
Nifedipine
L-type Ca2+ antagonist. It is a dihydropyridine, which preferentially binds to the inactivated form of the channel, so has a selectivity for vascular tissue (which undergoes prolonged periods of depolarization.) Used to treat hypertension and angina pectoral as it can cause both coronary and peripheral vasodilation.
Verapamil
L-type Ca2+ channel antagonist. It is a phenylalkamine that binds to a different site from the DHP, but decreases the affinity of DHP binding. It shows greater use dependence and a more prolonged block than produced by the DHPs. Anti-dysrhythmic uses.
Diltiazem
L-type Ca2+ antagonist. A benzothiazepine that binds to a site different to the DHP, but increases the affinity of DHP binding. Produces a more use dependent and prolonged block than the DHP.
Diazoxide, Minoxidil, Nicorandil.
K+ channel openers that acts on K+ATP channels. The increased K* effluent leads to hyperpolarisation which results in smooth muscle relaxation. Potential clinical applications in the treatment of IBS, asthma and male alopecia. They are useful in the treatment of hypertension, however their action on insulin release leads to decreased glucose tolerance and hyperglycemia.
Tolbutamide and Glibenclamide
Orally acting anti-hyperglycemic agents. Sulphonylureas bind to sulphonylurea Rs on sites associated with the K+ATP channel. This results in β islet cell depolarization, Ca2+ influx and insulin release . Used in the treatment of NIDDM.
