Depression Medicinal Chemistry (Dr. Ali) flashcards |

This is a Free Service provided by Why Fund Inc. (a 501 C3 NonProfit) We thank you for your donation!


(1. Click on the course Study Set you wish to learn.) (2. If you wish you can click on "Print" and print the test page.) (3. When you want to take a test...click on anyone of the tests for that Study Set.) (4. Click on "Check Answers" and it will score your test and correct your answers.) (5. You can take all the tests as many times as you choose until you get an "A"!) (6. Automated college courses created from lecture notes, class exams, text books, reading materials from many colleges and universities.)

๎„?

Long-Term Learning

Learn efficiently and remember over time.

Start Long-Term Learning

Get personalized study reminders at intervals optimized for better retention.
Track your progress on this set by creating a folder

Increase in amine activity (dopamine) leads to ___.

Mania

Decrease in amine activity (NE, serotonin) leads to ___.

Depression

Controls moods, behavioral changes, wakefulness, appetite and sexuality.

Serotonin

Control wakefulness and alertness.

Norepinephrine

Increase in this amine will lead to schizophrenia and mania.

Dopamine

Decrease in this amine will lead to problems with motor function and Parkinson's.

Dopamine

What is the normal action of monoamine oxidase?

Inactivation of biogenic amines (NE, 5-HT, DA) by converting them to aldehyde and then subsequent oxidation

Non-selective irreversible MAOIs
(Hyrdazine derivatives)

Iproniazid (Anti-TB)
Phenelzine (Antidepressant)
Tranycypromine (Antidepressant)

3 metabolic pathways of phenelzine.

1. Oxidative deamination
2. Oxidative deamination and p-aryl hydroxylation
3. N-acetylation (minor)

Tranylcypromine was drug designed from ____.

Amphetamines
(Cyclopropyl analogue of amphetamine)

People taking tranylcypromine should avoid _____.

Foods containing tyramine

Selective irreversible MAO-B inhibitor

Selegiline

Selective irreversible MOA-A inhibitor

Moclobemide

Moclobemide options for metabolism?

1. Oxidative opening of morpholine ring
2. N-oxidation
3. Oxidative N-dealkylation
4.

3ry amine TCAs

Imipramine
Amitriptyline
Clomipramine
Doxepin
Trimipramine

2ry amine TCAs

Desipramine
Nortriptyline
Protriptyline

Non-cyclic SNRIs

Venlafaxine
Duloxetine

TCAs have spatial similarity to ____ and ____.

NE
5-HT

TCAs have affinity for both ____ and ____ meaning they are ____.

NE
Serotonin
Non-specific

1st TCA antidepressant

Imipramine

3ry TCAs have more affinity for ____ than ____ compared to 2ry amines. This means they will have ____ side effects.

5-HT
NE
Less

Imipramine metabolism pathways

1. N-demethylation of 3ry amine (--> desipramine)
2. 2-hydroxylation

Desipramine is ______ than imipramine, has ____ anticholinergic side effects and sedation.

More active
Less

T/F: Amitriptyline is photosensitive and should be protected from light?

True

All tertiary TCAs show _____ due to 1st pass metabolism.

Low bioavailability

Amitriptyline is converted to _____ by _____.

Nortriptyline
N-demethylation of the 3ry amine

Most powerful TCA ever made

Clomipramine

Which isomer of doxepin of more pharmacologically active?

Z (cis) isomer;
However it is used as a mixture.

Which are the non-tricyclic SNRIs?

Venlafaxine
Duloxetine

What are the benefits of non-tricyclic antidepressants?

No unwanted side effects that the TCAs contain.

O-demethylation of Venlafaxine creates the compound _____, which is ______.

Desmethylvenlafaxine (ODV)

Active

Venlafaxine is ____ times more selective for SERT than NET.

30x

Another name of Desmethylvenlafaxine is....

Desvenlafaxine

Desvenlafaxine can be used in patients with....

Hepatic insufficiency

N-demethylation of duloxetine leads to ______, which is an _____ compound.

An intermediate (?)

Active

Duloxetine is an inhibitor of _____. (CYP enzyme)

CYP2D6

NE selective reuptake inhibitors (4 characteristics)

- 3rd generation antidepressants
- Better selectivity than TCAs
- No action on cholinergic/adrenergic receptors
- Speeds up onset of action

Protriptyline differs from the other TCAs by having _____.

An unsaturated 10,11 ethylene bridge

Nortriptyline is the major metabolite of _____.

Amitriptyline

T/F: 2ry amines inhibit the reuptake of NE>5-HT

True

T/F: NE selective reuptake inhibitors have less anticholinergic/sedating side effect.

True

R-(-)-Atomoxetine

- Non-tricyclic 2ry amine antidepressant
-R isomer is 10x more active than S isomer
- It has less anticholinergic and cardiovascular side effects

Nisoxetine

- Non-tricyclic 2ry amine antidepressant
- Never marketed
-R isomer is 20x more selective than S isomer
- 3ry amine analogue is 100x less active to inhibit NET

The ______ carbon is highly susceptible to oxidation.

Benzylic

Reboxetine

- Non-tricyclic 2ry amine antidepressant
- Marketed as a racemic mixture, but activity is only with S,S- reboxetine
- 1st pass has not effect on absorption due to high oral bioavailability.

3-CF3 on the SAR of SNRIs will _____ activity of the drug.

Increase

Substituents on the position 2 carbon that will increase selectivity/activity of SNRIs?

-OCH3
-SCH3
-CH3
-F
-I

Substituents on the position 4 carbon that will increase selectivity/activity of SNRIs?

-CF3
-NH2
-OCH3
-CH3

-CF3 substitution at position 4 carbon on an SNRI makes it this compound?

Fluoxetine

What is the drug of choice for the treatment of depression?

SSRIs

T/F: SSRIs are used for both depression and anxiety?

True

Onset of action for SSRIs?

Slow: 2-6 weeks

T/F: SSRIs have a negative effect on libido?

True

Fluoxetine main pharmacophore?

Phenoxyphenyl propylamine

Which drug is the prototype of SSRIs?

Fluoxetine

-CF3 substitution at the 4 position carbon of SSRIs _____.

Makes them selective for SERT

-CF3 is an ______ group.

Electron withdrawing group

N-demethylation of fluoxetine will lead to ____, which is ______ active.

Norfluoxetine
10x more

Paroxetine is a ____ of fluoxetine.

Constrained analog

T/F: Citalopram undergoes first pass metabolism.

False
(High oral bioavailability)

More active enantiomer of Citalopram?

S-enantiomer

Escitalopram is the ____ isomer of Citalopram.

S

Escitalopram is ____ times more active than Citalopram.

2

Escitalopram is ____ times more potent than the R-isomer.

27

Sertraline is a constrained analog of _____.

Diphenylpropylamine

Oral bioavailability of _____ mean sertraline will _____.

20-36%
Undergo first pass metabolism

The major metabolite of sertraline is _____ potent as an SSRI and therefore _____.

5-10x less
Not clinical significant

The major metabolite of sertraline is called...

Desmethylsertraline

Which group on fluvoxamine is ESSENTIAL for its SERT activity?

Electronegative group on benzene ring (e.g. -CF3)

T/F: Fluvoxamine should be protected from light not to be inactivated by Z-isomer.

True

Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)

Mirtazapine

Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs) mode of action

Promotes the release of NE and 5-HT
- Blocks alpha-2 receptos on the presynaptic neuron and 5-HT2 and 5-HT3 receptors on the postsynaptic neuron

Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs) main side effects

Weight gain
Postural hypotension
No CYP related drug interaction have been reported

Serotonin antagonist/reuptake inhibitors (SARIs)

Trazodone

Trazodone mode of action

5-HT2A antagonist
Weak inhibitor of 5-HT reuptake

NE-Dopamine Reuptake inhibitors (NDRIs)

Bupropion

Bupropion mode of action

Selective dopamine reuptake inhibitor
Weaker 5-HT and NE reuptake inhibitor

T/F: Bupropion undergoes 1st pass metabolism due to low oral bioavailability.

True

T/F: Bupropion is associated with weight gain and sexual dysfunction

False

T/F: Bupropion has a long duration of action because it has active metabolites.

True

Bupropion is a potent inhibitor of ____ (CYP enzyme).

CYP2D6

Please allow access to your computerโ€™s microphone to use Voice Recording.

Having trouble? Click here for help.

๎€˜
๎€—

We canโ€™t access your microphone!

Click the icon above to update your browser permissions above and try again

Example:

Reload the page to try again!

Reload

Press Cmd-0 to reset your zoom

Press Ctrl-0 to reset your zoom

It looks like your browser might be zoomed in or out. Your browser needs to be zoomed to a normal size to record audio.

Please upgrade Flash or install Chrome
to use Voice Recording.

For more help, see our troubleshooting page.

Your microphone is muted

For help fixing this issue, see this FAQ.

Star this term

You can study starred terms together

๎€ 
Voice Recording

This is a Plus feature

๎€ 

๎€ 
๎€‚ Create Study Set