Agonists and Antagonists Flashcards
What are AMPA receptor agonists?
Glutamate and AMPA (the latter causes fast desensitisation)
What are AMPA receptor antagonists?
NBQX (competitive) and Telampanel (non-competitive)
What are the positive allosteric modulators of AMPA receptors?
Cyclothiazide, ampakines and LY404187
What are kainate receptor agonists?
Kainate, glutamate and domoate
What are kainate receptor antagonists?
CNQX and ACET
Which kainate antagonist is selective for GluK1?
ACET
What is the glu site agonist that binds at the SIS2 domain of GluN2A?
NMDA
What are the competitive Glu site antagonists that bind to the S1S2 domain of GluN2A-D?
R-AP5 and (R)-CPPene
What are the glycine site agonists that bind at the S1S2 domain of GluN1?
Glycine and D-Serine (but affinity of glycine for GluN1 is dependent on GluN2 tetramer)
What are the Glycine binding site antagonists at S1S2 domain of GluN1?
Kyurenate (endogenous) and 5,7-DCKN (synthetic)
What is the antagonist at the N-terminal domain of GluN2B leading to inhibition of NMDA receptors?
Eliprodil - it binds to the dimer interface between GluN2B and GluN1 subunits
What are the uncompetitive antagonists/channel blockers of NMDA receptors?
Ketamine, Memantine - low affinity
Phencyclidine (PCP)
MK-801 - high affinity, withdrawn from trials
What can block the pore of a glycine receptor?
Picrotoxin
What potently inhibits glycine receptors?
Strychnine and RU5135
What are the agonists of GABA A receptors?
GABA, gaboxadol, muscimol the psychoactive constituent of Amanita muscaria
What are the orthosteric (competitive) antagonists of GABA A receptors?
Dicentra cucullaria (Dutchman’s breeches), bicuculline and GABAzine
What are the non-competitive antagonists of GABA A receptors?
Anamirta cocculus, picrotoxin and U93631
What are allosteric modulators of GABA A receptors?
Benzodiazepines, barbiturates, anaesthetics and alcohol
What effect do benzodiazepines has on GABA A receptors?
Positive allosteric modulators - increase frequency of bursts of channel opening
What are inverse agonists of the benzodiazepine binding site on GABA A receptors?
DMCM (which is seizure promoting and anxiogenic) and flumazenil (also promotes anxiety but used to treat overdose)
Barbiturates directly activate GABA A receptors at high doses, what do they do at low doses/concentration?
They are positive allosteric modulators at lower doses.
Barbiturates tend to increase the duration of bursts of channel opening of GABA A receptors which means…
there is not a large toxicology window
Which anaesthetics target GABA A receptors?
Etomidate, propofol and pentobarbitol (Group 1 - IV anaesthetics)
Which receptors do the Group 2 anaesthetics (nitrous oxide, ketamine, xenon and cyclopropane) target?
NMDA receptors, AMPA receptors, neuronal acetylcholine receptors and 2 pore potassium channels
Which receptors do the Group 3 anaesthetics (halogenated ethers e.g. isofluorane and alkanes e.g. halothane, chloroform) target?
GABA A receptors, glycine receptors, NMDA receptors, AMPA receptors, neuronal ACh receptors, 2 pore potassium channels.
Parasympathomimetic drugs exert a similar action to which neurotransmitter?
Acetylcholine
What are examples of parasympathomimetic drugs?
Metacholine, carbachol, muscarine - drugs that directly stimulate cholinergic receptors
What are examples of drugs that inhibit the cholinesterase enzyme?
Phyostigmine (used in glaucoma eyedrops) and neostigmine (used in treatment of myasthenia gravis)
What parasympathomimetic drugs have irreversible effects?
Parathion (an insecticide) and DFP (a toxic nerve gas)
What are examples of sympatholytic drugs?
Guanethidine, reserpine and methyldopa
What are some examples of sympathomimetic drugs?
Ephedrine, amphetamine and tyramine
Which drugs increase alpha adrenergic receptor activity?
Methoxamine and phenylepinephrine
Which drugs decrease alpha adrenergic receptor activity?
Phenoxybenzamine, phentolamine, prazocin (alpha1) and yohimbine (alpha2)
Which drugs increase beta adrenergic receptor activity?
isoproterenol and the beta2 stimulators salbutamol and terbutaline
Which drugs decrease beta adrenergic receptor activity?
propranolol and metaprolol (both beta blockers) and atenolol (beta1) and butoxamine (beta2)
How does cocaine increase spatial and temporal distribution of dopamine?
By antagonism of dopamine transporter (DAT), norepinephrine transporter (NET) and serotonin transporter (SERT) preventing reuptake of dopamine from the synaptic cleft.
How does amphetamine increase dopamine signalling?
It provides an alternative substrate to amines which usually couple with the co-transporters DAT and NET so is therefore a competitive antagonist at this site. When it alters the vesicular monoamine pump VMAT-2 it leads to long-lasting rewiring.
How do SSRIs increase availability of 5HT in the synaptic cleft?
By blocking SERT
What are the 5HT receptor agonists triptans and ergot alkaloids used for?
Migraine treatment - they increase cerebral vasoconstriction to counteract cranial vasodilation by targeting 5HT1B/D/F. They are counter indicated in CVD as 5HT1B is also found in peripheral smooth muscle.
What is the anti-hypertensive 5HT2 receptor antagonist?
Ketanserin
What are the 5HT3 receptor antagonists tropisetron and ondansetron used for?
To prevent nausea and vomiting
What is the 5HT2C receptor agonist locaserin used for and why?
Obesity therapy as activation of 5HT2C receptor suppresses appetite.
LSD is an agonist of which receptor?
5HT2A receptor (but also full or partial agonist of 1A/B/D/E, 2C, 5A, 6 and 7)
Psilobycin is an agonist of which receptor?
5HT2A receptor (but high affinity for 2B and 2C, lower affinity for 1A and 1B)
How does MDMA act on neurons?
It enters neurons via monoamine transporters (SERT=NET>DAT) where it then inactivates VMAT2 and inactivates or reverses SERT, NET and DAT. It is also a weak agonist at 5HT1 and 5HT2 receptors.
Is cannabidiol an agonist or antagonist of CB1 receptors?
Antagonist
Is THC an agonist or an antagonist at CB1?
Partial agonist
What are two endogenous CB1 receptor agonists?
Anandimide (AEA) and 2-achidonylglycerol (2-AG)
Which endocannabinioid is more abundant in the human brain and has higher efficacy?
2-arachidonylglycerol (2-AG)
What are some examples of opiates (naturally occurring compounds that are usually derived from the resin of the opium poppy)?
Morphine, codeine and thebaine
What is an example of a morphine ester?
Prodrugs such as diacetylmorphine (heroin)
What are two examples of semi-synthetic opioids (derived from opium or morphine esters)?
Buprenorphine and oxycodone
What are some examples of synthetic opioids?
Fentanyl, pethidine, methadone and tramadol
What are some examples of endogenous opioids?
Enkephalins and endorphins
What is diacetylmorphine (heroin) rapidly metabolised into?
6-monoacetylmorphine and then morphine through rapid removal of acetyl groups.
Caffeine is an agonist or antagonist of adenosine receptors?
Competitive antagonist
