• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

Card Range To Study



Play button


Play button




Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

513 Cards in this Set

  • Front
  • Back

epinephrine aka?

hormone adrenaline

norepinephrine aka?

hormone noradrenaline

true NT of the sympathetic NS?



alpha and beta activity


more beta than alpha activity

ortho-dihidroxybenzene moiety aka?


class of pharmacologically active substances that contain both an amine and an ortho-dihidroxybenzene moiety?


many adrenergic ligands are?


cells bearing adrenergic receptors are called?

effector cells

act on effector cells or act on the neurons that release norepinephrine?

adrenergic drugs

can have a variety of physiological effects and regulate many processes implicated in disease?

adrenergic drugs

what kinds of peripheral effector cells are affected by stimulation of adrenergic receptors?

cardiac muscle, smooth muscle (lung bronchodilation), liver cells (gluconeogenesis, glycogenolysis), fat cells (lipolysis), secretory epithelia, connective tissue

key physiologic effects of stimulation of sympathetic NS?

increased HR and force of contractions, increased BP, shift in blood flow to skeletal muscles, dilation of bronchioles and pupils, increased blood glucose

where does the biosynthesis of norepinephrine take place?

in adrenergic neurons near the terminus of the axon and junction with the effector cells

first step in biosynthesis of norepinephrine?

active transport of L-tyrosine into the adrenergic neuron

rate-limiting step in norepinephrine biosynthesis?

tyrosine hydroxylase (feedback inhibition may occur)

describe the biosynthesis of norepinephrine?

L-tyrosine (through tyrosine hydroxylase) L-dopa (through aromatic L-amino acid decarboxylase) dopamine (through dopamine beta hydroxylase within storage vesicle) norepinephrine

describe the process of norepinephrine release?

depolarization of presynaptic terminal > activation of voltage dependent Ca channels > fusion of vesicles > release of norepinephrine onto effector cell > activation of adrenergic receptors

how are presynaptic alpha-2 receptors involved in norepinephrine termination?

provide feedback inhibition

how is most norepinephrine terminated?

active reuptake through NET (~95%)

what happens to NE once it undergoes reuptake into the terminal?

either recycled or metabolized by MAO

diffusion of NE to extraneuronal sites results in metabolism by?


how is NE metabolized in the presynaptic terminal?


subject to metabolism by COMT?

catechols (1, 2 diphenolic moiety)

often substrates of MAO?

drugs with aliphatic amino groups

how are adrenergic receptor subtypes encoded?

by distinct genes

what type of receptor are adrenergic receptors?


have 7 transmembrane helices?


binds G proteins and structural differences in this control the specificity for different G proteins?

intracellular loops

how to adrenergic receptor subtypes mediate distinct cellular responses?

through coupling to different G proteins

alpha-1 receptors are coupled to which G protein?


The Gq pathway is?

PLC > DAG + IP3 > DAG activates PKC, IP3 releases intracellular stores of Ca

alpha-2 receptors are coupled to which G protein?


The Gi pathway is?

inhibit adenylyl cyclase > reduce cAMP concentration

beta receptors are coupled to which G protein?


The Gs pathway works by?

stimulate adenylyl cyclase, increase cAMP concentration

used to treat shock, hypotension?

alpha-1 agonists

used as antihypertensives?

alpha-2 agonists

beta-1 antagonists

used as bronchodilators?

beta-2 agonists

GPCR binding with suitable conformational change to stimulate effector signaling cascade; endogenous drug or drug that is similar to NT describes?


GPCR binding without suitable conformational change and thus no signaling; drug with more complex structure than neurotransmitter or related agonist ligands describes?


minimal requirements for adrenergic agonist activity

primary or secondary aliphatic amine separated by two carbons from a subbed benzene ring

basic amino group

hydroxyl-subbed carbon in R configuration


nonselective beta agonist

beta-1 receptor side effects

what happens to selectivity as the amine of NE is substituted with larger, lipophilic groups?

beta receptor agonist activity increased, alpha receptor agonist activity decreased (large enough can become antagonists)


beta-2 selective agonist

small alkyl group (methyl or ethyl) substitutions at carbon next to amine group in NE structure have what effect? does this have an effect on duration of action for catecholamines?

slows metabolism by MAO, no as the structure is still a substrate for COMT

resistance to MAO activity more important in?

non-catechol, indirect-acting phenylethylamines


direct acting stereoisomer

define indirect-acting?

displacement of NE from vesicles or reuptake inhibition

what is unique about indirect-acting sympathomimetics in terms of metabolism?

not substrates for COMT and poor substrates for MAO

(1R, 2S)-ephedrine

direct and indirect activity

CNS activity and side effects

ephedrine activity?

direct and indirect

(1S, 2S)-pseudoephedrine

indirect activity

fewer CNS side effects than ephedrine

pseudoephedrine activity?



indirect activity

dramatic CNS stimulation and abuse potential

combined salts used for ADHD (Adderall)


indirect activity

dramatic CNS stimulation and abuse potential

combined salts used for ADHD (Adderall)

not even once


selective beta-2 agonist

orally active bronchodilator

catechol (3', 4'-dihydroxy) oral activity?


3', 5'-dihydroxy compounds metabolism and selectivity?

not substrates for COMT, provide beta-2 selectivity


selective beta-2 agonist

shorter acting

orally active bronchodilator

resistant to COMT

beta-2 agonist that is resistant to COMT?



selective beta-2 agonist

prevents premature labor, relaxes uterus


selective alpha-1 agonist

hypotension, dilation of pupil, nasal decongestant, causes vasoconstriction

altered substitution pattern and groups on the aromatic ring of the NE parent affords?

beta-2 selectivity

what must be present and where must it be present on the NE parent structure to retain beta activity?

hydrogen forming group at the 4' position (if it is the only hydrogen forming group on the ring, it must be at this position to retain beta activity)

presence of only 3'-OH on NE parent structure means what?

eliminates activity at beta receptors affording selective alpha-1 agonists

epi and NE oral activity?

none, metabolized by intestinal and liver COMT and MAO

both cause vasoconstriction and cardiac stimulation?

epi and NE

between epi and NE, which is more widely used?


used in hypotensive crisis (allergic rxn, anaphylaxis, alpha activity), cardiac arrest (beta activity), asthma (bronchoconstriction) and inhibits uterine contractions (beta-2 activity)?


phenylephrine, metaraminol, and methoxamine are what family of drugs?



alpha-1 selective agonist

minimal cardiac stimulation

not substrate for COMT

long duration

strong vasoconstrictor

used for hypotension treatment in surgery/shock


alpha-1 selective agonist

bioactivated by demethylation to active phenol

minimal cardiac stimulation

not substrate for COMT

long duration

strong vasoconstrictor

used for hypotension treatment in surgery/shock

OTC nasal decongestant with less than 10% oral bioavailability due to hydrophilicity and intestinal 3'-O-glucuronidation?



alpha-1 selective agonist


nasal decongestant and eye drop

what do bulky, lipophilic meta/para substituents do for selectivity?


xylometazoline, oxymetazoline, tetrahydrozoline, and naphazoline are what family of drugs?



alpha-1 selective agonist


nasal decongestant and eye drop


alpha-1 selective agonist


nasal decongestant and eye drop


alpha-1 selective agonist


nasal decongestant and eye drop


alpha-2A selective agonist


other uses: sedation, ADHD, nicotine and opiate withdrawal, glaucoma




open form of clonidine


open form of clonidine


alpha-2C selective agonist

muscle relaxant

reduces spasticity associated with cerebral or spinal cord injury

alpha-2 subtype associated with antihypertensives, antiglaucomas, ADHD drugs?


alpha-2 subtype associated with antispasmolytics and analgesics?


arises from replacing carbon with amine NH to form a guanidino group with the imidazoline ring (NH bridge)?

alpha-2 selectivity


beta-2 selective agonist

used as bronchodilator in asthma and other constrictive pulmonary conditions

oral dosage or inhalers

what can the longer acting nature of some beta-2 agonists be attributed to?

higher lipophilicity and greater affinity


beta-2 selective agonist

unique binding; "anchoring" by the phenyl group gives high affinity


beta-2 selective agonist

inhaled powder, fast onset

12 hour duration


beta-2 selective agonist

newest bronchodilator

24 hour duration (once daily)

also governs indirect versus direct activity?


no aromatic substitution allows for what in adrenergic drugs?

indirect activity

alpha antagonists are expected to be?


are more structurally removed from NE?

adrenergic antagonists

antagonists typical dosing?

once daily


alpha-1 selective antagonist


alpha-1 selective antagonist

contain quinazoline (far left) and piperazine (second from right) rings


alpha-1 selective antagonist

contain quinazoline (far left) and piperazine (second from right) rings


alpha-1A selective antagonist

N-group open chain

first line in BPH

no utility as antihypertensive


alpha-1A selective antagonist

N-group open chain

first line in BPH

no utility as antihypertensive


alpha-1A selective antagonist

N-group open chain

first line in BPH

no utility as antihypertensive

used to treat HBP, CV problems, glaucoma, migraines, generalized anxiety disorder, hyperthyroidism, certain types of tremors?

beta antagonists (blockers)

are beta blockers first line treatment?

no, often used in combination


beta antagonist


pronethalol aka arylethanolamine

beta antagonist


propranolol aka aryloxypropanolamine

beta antagonist



beta nonselective antagonist

multiple uses


beta nonselective antagonist

multiple uses


beta nonselective antagonist

multiple uses


beta nonselective antagonist

multiple uses


beta nonselective antagonist

multiple uses


beta-1 selective antagonist


beta-1 selective antagonist


beta-1 selective antagonist


beta-1 selective antagonist

what are NRIs?

NE reuptake inhibitors, a class of antideppressant


NE reuptake inhibitor


NE reuptake inhibitor


NE reuptake inhibitor

indications for treatment with serotonergic agents?

psychosis, irritable bowel, migraine, nausea, depression, emesis

derived from ergot, a grain fungus, and can cause psychadelic effects involving stimulation of 5-HT receptors in the CNS?


serotonin (5-HT)


3,5-disubstituted indole ring

(+)-lysergic acid diethylamide

what does 5-HT stand for?


name 3 biogenic amines?

serotonin, norepinephrine, dopamine

which NT is an indolalkylamine?


results in overproduction of 5-HT?

tryptophan loading

increase synaptic 5-HT and can be antidepressants, but are nonselective and interfere with metabolism of other NT and therapeutics?

MAO inhibitors

amino acid precursor for 5-HT?


rate limiting step in 5-HT synthesis?

tryptophan hydroxylase

where does tryptophan hydroxylase act on tryptophan?

in the neuron

which 5-HT receptor is a ligand-gated ion channel?


what kinds of ions go through 5-HT3 receptors?


which 5-HT receptors are GPCRs?


which 5-HT receptors are coupled to Gi and what is the effect of binding?

5-HT1,5; inhibit adenylyl cyclase, decrease cAMP

which 5-HT receptors are coupled to Gs and what is the effect of binding?

5-HT4,6-7; stimulate adenylyl cyclase, increase cAMP

which 5-HT receptors are coupled to Gq and what is the effect of binding?

5-HT2; PLC > PKC and IP3 > increase of intracellular Ca

describe the process of serotonin release?

depolarization of presynaptic terminal > activation of voltage dependent Ca channels > fusion of vesicles > release of serotonin > activation of serotonin receptors

which 5-HT receptor subtype is present on the presynaptic neuron and thus aids in feedback inhibition?


which 5-HT receptor subtypes are present o n the postsynaptic neuron or effector cell?

5-HT1-7 (all of them)

how is 5-HT signaling mainly terminated?

active transport reuptake by SERT

how is 5-HT metabolized?

MAO in presynaptic terminal and synaptic cleft

most widespread of all of the 5-HT receptors?


5-HT1A receptors exist in the CNS in high amounts in which areas?

cerebral cortex, hippocampus, septum, amygdala, raphe nucleus

5-HT1A receptors exist in the CNS in low amounts in which areas?

basal ganglia, thalamus

5-HT1A receptors in this area are largely somatodendritic autoreceptors?

raphe nucleus

main focus of drug development for 5-HT1A receptors is for?

treatment of anxiety and depression

first LCAP (long-chain arylpiperazine) to be approved as an anxiolytic agent?


important SAR for 5-HT1A binding?


many of these are nonselective and have activity at dopamine and adrenergic receptors?



5-HT1A LCAP agonist

first LCAP to be approved as an anxiolytic agent


5-HT1A LCAP agonist

useful as an antidepressant

could involve presynaptic 5HT receptors; increased feedback inhibition and lower serotonergic activity?

antianxiety actions

could involve postsynaptic 5-HT1A receptors?

antidepressant actions

could produce different clinical outcomes?

full versus partial agonism

5-HT1A receptor partial agonists are similar to agonists except for?

2-methoxyphenyl group

new classes of true antagonists bind pre-, post-synaptic 5HT-1A receptors or both?


can increase 5-HT concentration by blocking presynaptic feedback inhibition of 5-HT release?

5HT-1A receptor antagonists

are promising therapeutic agents for the treatment of depression?

5HT-1A receptor antagonists


5-HT1A receptor antagonist

also binds D2 and 5-HT2A receptors

can have antagonistic effects on full agonists?

weak partial agonists

dominant serotonin receptor subtype in cerebral blood vessels?


serotonin receptor in arterial smooth muscles that are the targets of triptans (agonists) used for the treatment of severe migraine (vasoconstriction)?


a migraine appears to begin when what becomes overactive?

trigeminal nucleus caudalis (TNC) system (causes blood vessels to dilate)

drugs that are tryptamine derivatives?


which drugs have poor selectivity for 5-HT1D receptors and also often bind 5-HT1B and 1F receptors?



5-HT1D agonist

original triptan


5-HT1D agonist

newer triptan with improved oral bioavailability and half-life


5-HT1D agonist

newer triptan with improved oral bioavailability and half-life


5-HT1D agonist

newer triptan with improved oral bioavailability and half-life


5-HT1D agonist


5-HT1D agonist


5-HT1D agonist


5-HT1D agonist


5-HT1D agonist

structural outlier, not a tryptamine derivative

identified early as 5-HT2 receptor antagonist with no affinity for 5-HT1 receptors; helped identify the 5-HT2 receptors?



5-HT2A/C, alpha-1, H1 receptor antagonist


5-HT2A receptor agonist

psychadelic mushrooms


5-HT2A receptor agonist

acts as full or partial agonist

from peyote, used by Nativ Americans in Mexico

activation of which receptor is necessary for the effects of "classic" psychadelics like LSD, psilocin, and mescaline?


effect of 5-HT2A receptor activation in the periphery?

reduction of intraocular pressure

5-HT2A agonists could be useful in the treatment of?


the goal of compounds used to reduce eye pressure?

reduce pressure without crossing BBB and causing hallucinogenic side effects

many of this type of drug's actions involve antagonism of 5-HT2A receptors?



5-HT2A, D2 receptor antagonist


alpha-1 activity too


5-HT2A receptor antagonist

antipsychotic, antianxiety


5-HT2A, D2 receptor antagonist

atypical antipsychotic

muscarinic acetylcholine activity too


5-HT2A, D2 receptor antagonist

schizophrenia, bipolar

very "dirty"


5-HT2A, D2 receptor antagonist

atypical antipsychotic


5-HT2A, D2 receptor antagonist

atypical antipsychotic


5-HT2A, D2 receptor antagonist

atypical antipsychotic

many hallucinogens bind which receptor and how do they act?

5-HT2A agonists (LSD for example)

5-HT2A drugs can selectively choose the A subtype instead of the C, but which receptor do they also often act on?



binds mostly D2

typical (classical) antipsychotic

nonselective (dirty)


binds mostly 5-HT2

atypical antipsychotic

which receptor is a member of the cys-loop family of ligand gated ion channels that includes nicotinic acetylcholine, GABA, glycine receptors, and Zn activated ion channels?


which receptor is a homomeric or heteromeric pentamer?


which receptor is an ion channel that opens in response to agonist binding to the extracellular domain and is cation permeable?


mainly used for treatment of chemo and radiation induced emesis and irritable bowel syndrome?

5-HT3 drugs

5-HT3 partial agonists are general used for?

IBS (investigational)

5-HT3 antagonists are generally used for?

emesis and IBS

5-HT3 receptor activation effect in the CNS?

emesis (brain stem), anxiety, seizures

5-HT3 receptor activation effect in the PNS?

abdominal pain and emesis

where is the vast majority (~95%) of all 5-HT found in the body?

gut, involved in regulating normal intestinal function

functional bowel disorder largely characterized by abdominal pain?


impacts quality of life for approximately 10-20% of the world population that is affected?


two major subtypes of IBS?

IBS-D (diarrhea predominant), IBS-C (constipation predominant)

what type of drug is given to treat IBS-D?

5-HT3 antagonist or partial agonist

what type of drug is given to treat IBS-C?

5-HT3 agonist or partial agonist

what are the SARs for 5-HT3 receptor agonists?

indole ring or equivalent with amine side chain

aromatic with piperazine ring (quipazine analogs)


one of parent structures for SAR of 5-HT3 receptor agonists

what is the N4-piperazine nitrogen in quipazine important for?

binding (N1 nitrogen is not)

what is the quinoline nitrogen in quipazine required for?

high affinity

clinically useful for antiemetic properties?

5-HT3 antagonists (setrons)

what head group is typically found in 5-HT3 receptor antagonists?


which functional group is indicative of a second generation "setron"?

imidazole ring

activity of the second generation "setrons" is defined generally by?



5-HT3 antagonist


5-HT3 antagonist

5-HT4 receptors are coupled to which pathway and binding produces what effect?

Gs, stimulates adenylyl cyclase, increase cAMP

how do the multiple isoforms of 5-HT4 receptors vary?

in their intracellular C-terminal region

located in the GI tract, urinary bladder, heart (atrium), adrenal gland and CNS?

5-HT4 receptors

5-HT4 receptor antagonists have been developed for the treatment of what?


which agonists have some structural crossover with 5-HT3 ligands?


many 5-HT4 agonists are?



5-HT3, 4 antagonist


5-HT3, 4 antagonist

which NT helps stimulate gut motility?


5-HT4 receptor agonists can be used for?


5-HT4 receptor antagonists can be used for?


what is responsible for the termination of serotonergic transmission?


agents that block this can increase synaptic 5-HT?


can be useful in the treatment of depression, OCD, panic disorders?

SERT blocking agents

structure is similar to that of NET and DAT?


SSRI stands for?

selective serotonin reuptake inhibitor

SNRI stands for?

selective norepinephrine reuptake inhibitor

NSRI stands for?

norepinephrine and serotonin reuptake inhibitor

DNRI stands for?

dopamine and norepinephrine reuptake inhbitor

serious depression that interferes with the ability to work, study, eat, sleep, and enjoy?

major depressive disorder

treatment for this can include antidepressants, psychotherapy, and electroconvulsive therapy?

major depressive disorder

mild, chronic depression that lasts for 2 years or longer (1 year in children and adolescents) that is less severe?

dysthymia, persistant depressive disorder

treatment for this can include antidepressants and psychotherapy?

dysthymia, persistant depressive disorder

characterized by cyclical periods of depression and mania with varying duration, frequency, and intensity?

bipolar disorder, manic-depressive illness

treatments for this can include "mood stabilizers" and antipsychotics in combination with antidepressants?

bipolar disorder, manic-depressive illness

what is the monoamine hypothesis?

depression results from a deficiency in serotonin and/or norepinephrine

which type of antidepressant drugs had considerable side effects and are therefore not used anymore?

MAO inhibitors

major pharmacologic treatment for depression but affect many other systems in addition to inhibiting monoamine uptake?

tricyclic antidepressants (TCAs)

have improved safety and tolerability compared to TCAs?


the majority of antidepressants in current use employ which mechanism of action?

inhibition of reuptake of 5-HT and/or NE

desipramine, nortriptyline, and atomoxetine are?

selective norepinephrine reuptake inhibitors (SNRIs)

citalopram, escitalopram, fluoxetine, paroxetine, sertraline are?


amitriptyline, duloxetine, imipramine, venlafaxine are?

norepinephrine and serotonin reuptake inhibitors (NSRIs)

bupropion is what type of drug?

dopamine and norepinephrine reuptake inhibitor (DNRI)

what opportunity is created by variation in selectivity for serotonin and norepinephrine?

treatment of different symptoms

broader antidepressant activity if?

both NET and SERT inhibited

limitations to current antidepressant treatments?

low remission rates, delayed onset of action, side effects, drug-drug interactions

5-HT2A drug side effects?

insomnia, anxiety/agitation, and sexual dysfunction

5-HT2C drug side effects?

irritability and decreased appetite

5-HT3 drug side effects?

nausea, vomiting, headache

why do antidepressants have a delayed onset of action?

adaptive changes must occur with chronic administration of SSRIs and NSRIs (many theories)

which CYPs metabolize antidepressants?


proven treatments for depression, OCD, and panic disorder with reduced adverse effects compared to TCAs?


first SSRI?



first SSRI

long term admin of SSRIs causes?

adaptibe changes in the serotonergic system

which SSRI contains a 4 carbon side chain unlike the 3 carbon side chain of 5-HT and the other SSRIs?


fluoxetine, paroxetine, and citalopram are what kind of SSRIs?

phenoxyphenylalkylamine SSRIs

many SSRIs contain EWG on which position and what does this do?

para position, adds SERT selectivity and reduces metabolism







4 carbon chain

which drugs have the potential to produce serotonin syndrome?


symptoms of this include agitation, sweating, diarrhea, fever, hyperreflexia, incoordination, confusion, myoclonus, shivering, tremor?

serotonin syndrome

what do the 5-cyano and 4-fluoro gorups do for citalopram?

yield high selectivity for SERT

which enantiomer of citalopram is active?


one of the most SERT-selective inhibitors and therefore has few side effects?


which SSRI has less potential for drug-drug interactions as a result of weak CYP inhibition and less plasma protein binding?


structurally distinct from other SSRIs due to a rigid bicyclic system?


have prolonged half lives and require long washout periods before switching to another antidepressant?


extensively metabolized to pharmacologically active N-demethylated metabolites when possible and excreted in urine and feces?




rigid bicyclic system

which SSRI can undergo glucuronidation as part of its metabolism?


often inhibit both NET and SERT but bind to other targets leading to side effects?


have been reported to produce a faster and greater antidepressant response compared to an SSRI alone?


active metabolite of venlafaxine?





NSRI that is a phenylethylamine with a 2 carbon chain?


drug that is associated with withdrawal problems and requires a slow taper?


30-fold more potent at inhibiting SERT over NET but acts at both?


5-fold more potent at inhibiting SERT over NET and more potent than venlafaxine?


demonstrates less off-target binding (lower adverse effects) and has a unique crossover into chronic pain treatment?



antidepressant that is structurally related to CNS stimulants?


this antidepressant is a nicotinic antagonist and it and its metabolites are essentially indirect acting adrenergic and dopaminergic agonists?


antidepressant that is indicated for the treatment of MDD and as an aid in smoking cessation?


bupropion is activated by which CYP?


antidepressant that is a DAT blocker like methamphetamine and also blocks NET?


antidepressant that is a potent CYP2D6 inhibitor?



excitatory amino acid NT


inhibitor amino acid NT

provide most of the excitatory and inhibitory neurotransmission in the NS?


what are the NT criteria?

presence of the substance within presynaptic cells, must be released from terminals upon stimulation, must have action on postsynaptic cells, must have a mechanism for removal/termination

main excitatory NT in CNS?


actions of other excitatory NT are mediated through?

glutamate receptors/transporters

main inhibitory NT in the CNS?


another important inhibitory NT?


actions of other inhibitory NT are mediated through?

GABA and glycine receptors/transporters

influx of positive ions in neurotransmission leads to?

depolarization > AP (neuronal firing)

influx of negative ions or efflux of positive ions in neurotransmission leads to?

hyperpolarization > resting state (no neuronal firing)

what determines whether the actions in neurotransmission are excitatory or inhibitory?

ion selectivity

essential for CNS processes like perception of pain, neuronal development, memory, learning?

glutamateric neurotransmission

why are there so few FDA-approved glutamatergic drugs?

because the glutamate system is essential and very sensitive to manipulation

glutamate is synthesized in the neuron from glutamine via?


glutamate transported into vesicles by?


glutamate activates which kinds of postsynaptic receptors upon release?

metabotropic (GPCR) and ionotropic (ligand-gated ion channels)

very important to the termination of the glutamatergic signal?

astroglial uptake of glutamate via EAATs

which transporter is responsible for the uptake of glutamate?

excitatory amino acid transporter (EAAT)

glial cells aka?


what happens to glutamate inside of astrocytes

glutamate converted to glutamine via glutamine synthetase

what is the purpose of switching glutamate back to glutamine?

allows silencing of glutamate and shuttling between cells

what happens to glutamine once it has been processed by the glial cell?

secreted by glial cell, taken up by the neuron, and converted back to glutamate and packed back into vesicles

what kinds of receptors are NMDA, AMPA, and kainate receptors?


what is the effector for the group 1 metabotropic receptors?


what is the effect for the group 2 metabotropic receptors?

decreased cAMP

what is the effect for the group 3 metabotropic receptors?

decreased cAMP

have distinct expression patterns in the CNS in terms of both cell types and regions?

metabotropic glutamate receptors (selective drug effects?)

drugs that target which types of glutamate receptors are in general better tolerated?


are there any metabotropic glutamate receptor drugs yet?


potential applications of mGluR allosteric modulators in CNS diseases? (very active area of drug discovery)


PAM stands for?

positive allosteric modulator

NAM stands for?

negative allosteric modulator

what kinds of ions do NMDA, AMPA, and kainate receptors deal with?


ionotropic glutamate receptors are formed by how many subunits?

4 (tetrameric)

can an NMDA receptor be made up of subunits from the AMPA receptor class?


in the continuous presence of agonist, the interface between two agonist binding domains can become unstable leading to the closure of the ion channel with agonist still bound which is a process called?


how does glutamate binding trigger opening of an ion channel?

binding causes closure of the cleft in the agonist binding domain which pulls lower lobes of agonist binding domain apart which triggers opening of ion channel

what part of the AMPA receptor is critical for agonist binding?

conserved arginine in the receptor

how do ionotropic glutamate receptor agonists interact with the receptor?

agonist interacts via its carboxylate group with the arginine in the upper lobe of the receptor


positively charged nitrogen

negatively charged acidic oxygens


postively charged nitrogen

negatively charged acidic oxygen near nitrogen


positively charged nitrogen

negatively charged acidic oxygens

glutamate agonists must form contacts between?

amino acid moiety of agonist and upper lobe of the agonist binding domain

NMDA is an analog of?


AMPA is an analog of?


kainate is an analog of?


how must the glutamate agonist interact with the lower lobe?

in a manner that induces closure of the agonist binding domain

how do glutamate agonists interact with the lower lobe?

through a carboxylate or equivalent bioisostere

NMDA receptors can be activated by analogs of which AA?


which glutamate receptor agonists share similar SARs?

AMPA and kainate

how can you spot a glutamate analog?

alpha, beta, gamma

can be both aspartate and glutamate analogs?

NMDA receptor agonists

bulky substitutions are generally tolerated on the agonists of which glutamate receptor(s)?

AMPA and kainate

why are bulky substituents poorly tolerated by NMDA receptors?

tyrosine residue caps the lower portion of the binding socket, there is no room

what are the two MOAs of ionotropic glutamate receptor antagonists?

antagonists bind the conserved arginine and shield it to prevent agonist binding

antagonists bind similarly to agonists but are longer and unable to induce agonist binding domain closure

NMDA receptor antagonist primary mechanism?


AMPA and kainate receptor antagonist primary mechanism?


how can a shielding glutamate receptor antagonist be spotted?

hidden amino acid moiety

many are 2,3-quinoxalinediones

how are ionotropic glutamate receptor agonists and antagonists tolerated?

poorly and produce severe side effects

over-activation of which NT can cause seizures and neuronal death?


over-inhibition of glutamate can cause?

sedation, psychosis, and also neuronal death

agents that lower activity of ionotropic glutamate receptors could be useful for?


how do NMDA channel blockers work?

same way Mg blocks receptors in membrane potential dependent manner

are NMDA channel blocker selective?


NMDA receptor block is not relevant to clinical effect of this drug but abuse potential is mediated by NMDA receptors?


NMDA receptor channel blockers must be?

positively charged


NMDA receptor channel blocker

treats AD


NMDA receptor channel blocker

treats AD

fast kinetics

phencyclidine (PCP)

NMDA receptor channel blocker

slow kinetics


NMDA receptor channel blocker

fast kinetics


NMDA receptor channel blocker


NMDA receptor channel blocker

only work when the membrane potential is negative?

NMDA channel blockers

which NMDA channel blockers are well tolerated and useful for neuroprotection?

fast kinetics

which NMDA channel blockers produce severe adverse effects including dissociative and psychomimetic effects?

slow kinetics

which drugs induce all symptoms of schizophrenia?

NMDA receptor channel blockers

enhancement of NMDA receptor transmission via glycine site agonists does what?

improves symptoms in schizophrenia

mice with a partial deletion of GluN1 NMDA receptor subunit showed?

behavior abnormalities resembling schizophrenia

has rapid and potent antidepressant effects in treatment resistant MDD and bipolar depression?


NMDA receptor channel blocker

a single dose of this NMDA receptor channel blocker rapidly resolves suicidal behavior?


have high response rates in treatment of resistant MDD?

ketamine, other channel blockers

rapid and sustained antidepressant effect following a single injection of?


currently in clinical trials for the treatment of MDD?

ketamine, other channel blockers, GluN2B selective antagonists

GABA levels in the CNS are?

very high

anxiolytic and anticonvulsant effects, sedation, general anesthesia, coma and death are the effects of enhanced?

GABAergic transmission

anxiety and hyperexcitability, seizures and status epilepticus, and death are the effects of decreased?

GABAergic transmission

important therapeutic target for anxiolytics, sedatives, anticonvulsants, anesthetics?

GABAergic system

rate-limiting enzyme in GABA biosynthesis?

GAD (glutamic acid decarboxylase)

how do the concentrations of GAD compare to that of GABA?


GABA can be synthesized from?

glutamate via glutamate decarboxylase

enables synthesis of glutamate from alpha-ketoglutarate in the GABAergic presynaptic neuron?

GABA-T mitochondrial

is GABA-T reversible?


GABA metabolism is linked to?

the Krebs cycle

increase levels of GABA by inhibiting metabolism by GABA-T?




pi bond matters

acetylenic GABA


pi bonds matter



pi bonds matter

GABAergic neurotransmission is terminated through?

active uptake by GABA transporters (GATs) into both the presynaptic neuron and astroglia

how many GAT subtypes exist in both neurons and glia cells?



GAT inhibitor


how is GABA removed?

by active uptake into both the presynaptic neuron and astroglia

how does GABA get back to terminal after uptake into the astroglia?

via the glutamate-glutamine cycle

which GABA receptor is a ligand-gated ion channel?


which ion does GABAa select for?


which GABA receptor is a GPCR?


which pathway is GABAb coupled to and what is the effect?

Gi, decreased cAMP

GIRK channels

are obligatory dimers of B1 and B2 subunits?

GABAb receptors

which part of GABAb does GABA bind?

B1 subunit

cellular responses to GABAb activation depend on?

their location

presynaptic activation of GABAb receptors leads to?

inhibition of Ca channels, reduced cAMP (reduced NT release overall)

postsynaptic activation of GABAb receptors leads to?

activation of K channels (GIRKs) (hyperpolarization)

reduction of cAMP (regulation of gene expression)

how many types of GABAb receptors are there?



selective GABAb agonist

muscle relaxant for spasticity

adverse side effects such as exacerbation of seizures, reduction of cognitive function, insomnia


selective GABAb antagonist

do GABAb receptors bind GABAa agonists or antagonists?


are GABAb receptors modulated by benzodiazepines?


what might GABAb antagonists be good for treating?

mild cognitive impairment by indirectly increasing glutamatergic transmission

what are the two combinations in which GABAa subunits come together to form pentamers?

2 alpha + 2 beta + gamma

2 alpha + 2 beta + delta

where does GABA bind the GABAa receptor and how many GABA are required for binding?

alpha-beta interface, two GABA

where do benzodiazepines bind GABAa receptors?

alpha-gamma interface (or alpha-delta)

what are the two types of GABAa receptors?

extrasynaptic and synaptic

what is special about alpha-4 and alpha-6 containing GABAa receptors?

not sensitive to benzodiazepines because they contain delta subunits

which drugs are alpha-1 preferring "agonists" that bind to the benzodiazepine site?

Z drugs

alpha-5 is high in the hippocampus GABAa receptors and alpha-5 antagonists could do what?

improve cognition

alpha-1 in GABAa receptors does what?

mediates sedative effects

alpha-2 in GABAa receptors does what?

mediates anxiolytic effects


selective GABAa antagonist


GABAa agonist


GABAa agonist


GABAa agonist


GABAa antagonist (convulsant)

blocks GABAa receptors

clinically useful general anesthetic that enhances GABAa receptor activity?


vapour concentration that prevents patient movement in response to a supramaximal stimulus in 50% of subjects?


MAC relationship to potency?


how is the MAC of a volatile substance related to its lipid solubility?

inversely proportional


GABAa agonist

general anesthetic

has a specific binding site in the GABAa receptor

enhance GABAa receptor activity but directly open the GABAa receptor channel at high concentrations?


barbiturates are largely replaced by what drug in routine medical practice but are still used in general anesthesia and epilepsy?


where is the barbiturate binding site?

interface between the alpha and beta transmembrane domains of the GABAa receptor


GABAa agonist


controls convulsions and is used in assisted suicide and euthanasia

ligands at the benzodiazepine binding site are what?

allosteric modulators

what are the 4 groups of the ligands at the benzodiazepine binding site?

benzo agonists (PAMs)

non-benzo agonists (PAMs)

benzo inverse agonists (NAMs)

benzo antagonists (neutral ligand)

new non-benzo agonists aka?

Z drugs

what are the Z drugs?

zolpidem, zaleplon, eszopicolone


non-benzo agonist (PAM)

Z drug



non-benzo agonist (PAM)

Z drug



non-benzo agonist (PAM)

Z drug


indications for anxiolytics?

generalized anxiety disorder, phobic disorders, psychological factors affecting anxiety, panic disorder, OCD, PTSD

what kinds of drugs can be used for sleep disorders?


reduces anxiety and exerts a calming effect?

a sedative drug

produces drowsiness and reduces the latency to onset of sleep?

a hypnotic drug

what determines a drugs utility as either anxiolytics and/or sedative hypnotics?

PK and PD properties

sedative hypnotics drug classes?


Z drugs


major factors determining the clinical use of benzodiazepines?

rate and extent of absorption, presence and absence of active metabolites, degree of lipophilicity

a long acting benzodiazepine that has slow absorption, low lipophilicity, and active metabolites could be used for what purpose?


a short acting benzodiazepine that has rapid absorption, high lipophilicity, without active metabolites could be used for what purpose?


how do class A benzos differ from class B benzos?

class B benzos have a 1,2-annelation (extra ring)

benzo inverse agonists and antagonists are lacking in which SAR?

phenyl ring

do benzos and their metabolites bind plasma proteins?


how are benzos metabolized?

hepatic, microsomal oxidation including N-dealkylation and aliphatic hydroxylation, conjugation and excretion in the urine, rates vary

what is the problem with long lived benzo metabolites?

adverse effects, residual hypnotic effects, daytime drowsiness, oversedation, cognitive decline, confusion


GABAa agonist


rapid absorption, short half-life, one active metabolite

difference between benzos and Z drugs in terms of selectivity?

benzos non-selective of alpha units but Z drugs are more selective of alpha-1 (sedative effects)

absorbed faster than benzos, less side effects, better for sleep?

Z drugs

timeline of GABAa receptor sedatives?

barbiturates, benzos, Z drugs

how many approved barbiturates are there?


how can barbiturates form water soluble salts?

keto-enol tautomerization

produce dose dependent sedation?


replaced in routine treatment of sleep disorders but still used in general anesthesia, pre-op sedation, and acute treatment of seizures?


barbiturate adverse effects?

tolerance, dependence, potential for abuse, low toxicity threshold

an abnormal mental state involving a loss of contact with reality?


characterized by delusions, hallucinations, absent or inappropriate emotions, reduced motor activity?


symptom of psychiatric disorder and sometimes other causes?


are psychosis and schizophrenia the same thing?

no, symptoms of schizophrenia include psychosis

positive symptoms of schizophrenia?

hallucinations, thought disorders, delusions, disorganized behavior, catatonia

negative symptoms of schizophrenia?

social withdrawal, anhedonia, poverty of speech, emotional flattening

cognitive symptoms of schizophrenia?

memory, executive function, attention

core symptom of schizophrenia?

cognitive decline

risk factors contributing to schizophrenia?

genetic components, developmental errors caused by infections or trauma, autoimmune diseases, NT abnormalities, stress

is the risk of schizophrenia if one twin has it 100% for the other twin?


antipsychotics that block dopamine receptors are known as?


the hypothesis that enhanced dopaminergic neurotransmission leads to schizophrenia and decreasing it would reduce psychotic symptoms?

dopamine hypothesis

does not explain cognitive symptoms

history of antipsychotic treatment?

chlorpromazine (phenothiazine and thioxanthene neuroleptics)

haloperidol (butyrophenone neuroleptics)

clozapine (atypical antipsychotic)

primary action of neuroleptics?

reduce dopaminergic signaling in the mesolimbic-mesocortical pathways

how are neuroleptics supposed to work primarily?

as antagonists of D2 like dopamine receptors

what type of receptors are dopamine receptors?


which are the D1 like receptors and what is their effect?

D1 and D5, increase cAMP

which are the D2 like receptors and what is their effect?

D2, 3, and 4, decrease cAMP

which dopamine pathway is involved in motor control (Parkinson's)?

nigrostriatal system

which dopamine pathway is involved in reward (drug abuse)?

mesolimbic system

which dopamine pathway is involved in the symptoms of schizophrenia?

mesolimbocortical system

which dopamine pathway is involved in hormone release?

projections to the pituitary gland

which antipsychotic class is associated with extrapyramidal effects and only improve positive symptoms?

classical or typical antipsychotics

which receptors are altered in schizophrenic brains?

5-HT1A and 2Ai

is the serotonin hypothesis of schizophrenia correct?


induce synesthesia, pleasant perceptual perturbations?

psychadelics like LSD

act indirectly through the serotonergic system to enhance dopaminergic signaling in the striatum?

atypical antipsychotics

NMDA receptor channel blockers induce all symptoms of schizophrenia is a part of which hypothesis?

glutamate hypothesis of schizophrenia

have any drugs been developed based on the glutamate hypothesis for treatment of schizophrenia?


development began with antihistamines (sedatives) and ended with antipsychotics?

phenothiazine neuroleptics

achieved symptomatic relief of agitation and anxiety and had a reducing effect on psychosis?


initiated a new era in the drug therapy of the mentally ill?



typical antipsychotic

phenothiazine neuroleptic

chloride confers asymmetry

there must be 3 carbons separating nitrogen atoms


typical antipsychotic

which configuration of thioxanthene is the most active neuroleptic?


what is the benefit to long acting neuroleptics?

less side effects and better patient compliance

were discovered in an attempt to obtain more potent analgesics?

butyrophenone neuroleptics

how is haloperidol dosed?


neuroleptic associated with very high extrapyramidal side effects, less weight gain, little sedation, used in schizo and psych emergencies, used for Tourette syndrome and manic phase of bipolar?


neuroleptic that is short-acting, heavily sedating, anti-emetic, used in pre-op and psych emergencies?