Mechanisms of action Flashcards
What is the MOA of mirtazapine?
Noradrenaline and serotonin specific antidepressant.
5HT2A and 5HT2C antagonist, 5HT3 antagonist, H1 antagonist, alpha 1 and alpha 2 antagonist, moderate muscarinic antagonist. Presynaptic alpha 2 antagonist (which stimulates the release of NA and 5HT.
What is the MOA of venlafaxine?
Serotonin and noradrenaline reuptake inhibitor
What is the MOA of duloxetine
Serotonin and noradrenaline reuptake inhibitor
Weak inhibitor of dopamine reuptake
What is the MOA of reboxetine?
Noradrenaline reuptake inhibitor (NaRI)
What is the MOA of St John’s Wort?
Weak MAOi and weak SNRI
What is the MAO of trazadone?
Serotonin antagonist and reuptake inhibitor
Blocks serotonin reuptake pump (SERT) and also antagonist at 5HT2A and 5HT2C.
SERT blockage at 5HT1A is thought to be responsible for the antidepressant effect of SSRI but they also block SERT at 5HT2A and 5HT2C (thought to cause the side effects)
Trazadone has simultaneous effect of blocking SERT and also antagonising those receptors responsible for the SSRI side effects such as insomnia, sexual dysfunction and anxiety
What is the MOA of meclobemide?
Reversible inhibitor of MOA-A
What is the MOA of agomelatine?
Melatonergic antagonist (MT1 and MT2 receptor) and 5HT2C antagonist
What is the MOA of bupropion?
Norepinephrine-dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist
What is the MOA of donepezil?
Reversible acetylcholinesterase inhibitor
What is the MAO of tacrine ?
Reversible acetylcholinesterase inhbitor
What is the MOA of rivastagmine?
Reversible acetylcholinesterase inhibitor and butyrylcholinesterase inhibitor
What is the MOA of galantamine?
Selective, competitive and reversible inhibitor of acetylcholinesterase. In addition, galantamine enhances the intrinsic action of acetylcholine on nicotinic receptors, probably through binding to an allosteric site of the receptor
What is the MAO of memantine?
Non-competitive NMDA antagonist
What is the MOA of valproate?
GABA modulation - increases GABA in the brain, sodium channel inhibition and NMDA antagonist
What is the MOA of gabapentin?
Binds to the alpha-2-delta subunit of voltage-gated calcium channels, which reduces the release of certain neurotransmitters, including glutamate and substance P, and can help reduce neuronal excitability.
What is the MOA of topiramate?
GABA modulator, NMDA antagonist, and Na channel stabiliser
What is the MOA of carbamazepine?
Stabilises sodium channels
What is the MOA of phenytoin?
Stabilises sodium channels
What is the MOA of lamotrigine?
NMDA receptor modulation, stabilises Na channels and blocks calcium channels, some GABA modulation
What is the MOA of pregabalin?
Binds to the alpha-2-delta subunit of voltage-gated calcium channels, which reduces the release of certain neurotransmitters, including glutamate and substance P, and can help reduce neuronal excitability.
What is the MOA of benzos?
Enhance action of GABA by action of non-specific positive allosteric modulation of GABA-A, in the absence of GABA they have no effect on GABA functioning
What is the MOA of Z-drugs?
Enhance action of GABA by action of specific positive allosteric modulation of GABA-A (high affinity for α1-containing GABA-A receptors)
What is the MOA of buspirone?
Agonist of pre-synaptic and partial agonist of post-synaptic 5-HT1A subtype receptors, antagonist activity at D2 receptors (not linked to anxiolytic activity, indirect evidence for buspirone having a GABA antagonist-like action
What is the MOA of flumazenil?
Benzo antagonist
What is the MOA of propranolol?
Non-selective beta 1 and beta 2 beta-adrenergic receptor antagonist (beta blocker)
What is the MOA of amisulpride?
D2/D3 selective antagonist (low affinity selective antagonist of ‘D2 like’ receptors (D2=D3>D4) it has little affinity for D1 like’ receptors (D1 and D5) or non dopaminergic receptors (serotonin, histamine, adrenergic, and cholinergic)
What is the MOA of olanzapine?
dopamine and 5HT2 antagonism
What is the MOA of aripiprazole?
partial agonist at 5HT1A and D2, 5HT2A antagonist
WHat is the MOA of clozapine?
Dopamine and serotonin antagonist (5HT2A)
High affinity for D4, (to a lesser extent D1, D2, D3, D5) which may explain less EPSEs
5-HT1A partial agonist which may explain reduction of negative symptoms
Muscarinic M1, M2, M3, M5, histamine, and alpha-1 adrenergic-receptor antagonist
Norclozapine, the metabolite of clozapine, actively works on the M1 and M4 receptors.
What is the MOA of lurasidone?
Dopamine D2, 5-HT2A, 5-HT7, alpha2A- and alpha2C- adrenoceptor antagonist, and is a partial agonist at 5-HT1a receptors. Lurasidone does not bind to histaminergic or muscarinic receptors.
What is the MOA of cariprazine?
D3/D2 partial agonist
5HT1A partial agonism
5HT2B and 5HT2A antagonism
What is the MOA of raclopride?
D3/D2 antagonist - used in PET scans not therapeutically
What is the MOA of dexamfetamine?
Inhibiting dopamine and noradrenaline reuptake
What is the MOA of methylphenidate?
Inhibits DA and NA reuptake
What is the MOA of lisdexamfetamine?
Prodrug, absorbed by GI tract, converted to dexamfetamine which inhibits the reuptake of NA and DA. Converted by enzymes in red blood cells into dexamfetamine and L-lysine (amino acid). The activation of the prodrug results in longer action and a reduced abuse potential
What is the MOA of atomoxetine?
Targets the NET (noradrenaline transporter), inhibiting the reuptake of NA, therefore increasing NA levels in the synaptic cleft. Selective NA reuptake inhibitor
What is the MOA of guanfacine?
Selective agonist of α2A-adrenergic receptors. Binds to postsynaptic α2A-adrenergic receptors, mimicking NA
What is the MOA of clonidine?
Agonist of α2-adrenergic receptors, mimic NA
What is the MOA of methadone?
Mu-opioid receptor agonist, NMDA receptor antagonist, Inhibition of serotonin and norepinephrine reuptake
What is the MOA of lofexidine?
Alpha 2 agonist
What is the MOA of buprenorphine?
Partial agonist at the mu-opioid receptor?
What is the MOA of naloxone?
Pure opioid antagonist
Will reverse mu,delta and kappa
What is the MOA of naltrexone?
Long acting (compared to naloxone) opioid antagonist, targeting endogenous opioid receptors
(mu, delta, and kappa receptors), but particularly the mu-opioid receptor
What is the MOA of varenicline?
Nicotinic receptor partial agonist
What is the MOA of disulfiram?
Binds irreversibly to enzyme aldehyde dehydrogenase (ALDH) and causes acetaldehyde to accumulate following ingestion of alcohol. Elevated blood acetaldehyde causes facial flushing, severe headache, palpitations, tachycardia, hypertension, respiratory distress, nausea and vomiting. These symptoms commence within 15-30 min of ingesting alcohol and persist for several hours.
what is the MOA of acamprosate?
NMDA glutamate receptor antagonist and positive allosteric modulator of GABA-A receptor (effect on both receptors is indirect)
What is the MOA of selegiline?
Selective irreversible inhibition of MOA- B and inhibits MOA-A at higher doses
What is the MOA of sildenafil?
Inhibits cGMP-specific phospodiesterase type 5
What is the MOA of prazosin?
Alpha-1 adrenergic receptor antagonist
What does lurasidone not bind to?
Histamine H1 or muscarinic M1 receptors
Which illicit drugs interfere with ionotropic receptors or ion channels
Alcohol
Nicotine
Benzos
Ketamine
Which illicit drugs interfere with G coupled receptors
Opioids
Cannabinoids
GHB (y-hydroxybutyrate)
Which illicit drugs target monoamine transporters?
Amphetamine
Ecstasy
Cocaine
What illicit drugs target 5HT receptors?
Hallucinogens - LSD, psilocybin, DMT and mescaline
Which illicit drugs impact the glutamate system? (NMDA antagonists)
Dissociatives - ketamine, PCP, dextromethorphan, nitrous oxide
Which illicit drugs act on cannabinoid receptors?
THC
Which drugs act n GABA?
Benzos (GABA-A) and y-hydroxybutyrate (GHB - GABA-B)
How does cocaine work?
Blocks the dopamine transporter (DAT) -> increased dopamine in synaptic cleft
How do amphetamines work?
Binds to DAT and then taken up into the presynaptic axon terminal, increases monoamine neurotransmitters in the cytosol through the inhibition of vesicular monoamine transporter 2 (VMAT2) as well as through disruption of the electrochemical gradients necessary for the vesicular transporter function.
Inhibits the metabolism of monoamine transporters by inhibiting monoamine oxidase.
Stimulates the intracellular receptor TAAR1 inducing internalisation or transporter reversal of DAT.
All results in increased efflux of dopamine into the synaptic cleft and reuptake inhibition in the synaptic cleft through DAT internalisation and direct competition.
WHat class does caffeine belong to?
Xanthines
What is the primary mechanism of action of caffeine?
Antagonist of adenosine receptors
What is the function of adenosine ? What are the main receptor subtypes?
neurotransmitter that promotes sleep and relaxation
A1
A2A
