PSYC 04: Med Chem of Antidepressants

1) What is this structure of

2) Which drugs follow this structure

3) What does a substituent on orange (2) do

4) What does a substituent on yellow (4) do

5) Amine group (purple) forms what type of bonds (2)

6) The structure is a derived analogue of what

1) Phenoxy Phenyl Alkyl Amines

2) SSRIs

3) Increases NET affinity

4) Increases SERT affinity

5) Hydrogen bonds (w/ Asp98) and Cation-Pi (w/ Tyr95)

6) Diphenhydramine (antihistamine)

1) What 2 drugs are these

2) Which one is more potent (top or bottom + specify the drug name)

3) Therapeutic activity resides in the __ enantiomer (straight line or bolded line)

4) Figure out one way to identify these easily

1) Citalopram and escitalopram

2) Bottom; escitalopram

3) S (BOLD line)

4) Locate the ring and see a triple === 3, also a ring + F attached to amine

1) What is this drug

2) How can you tell what drug it is

3) This is a ____ analogue of ____

1) Paroxetine

2) Like Citalopram/Escitalopram. has a F attached to a ring ANDDD a ring with 2 oxygens attached to phenoxy

3) Constrained analogue of fluoxetine

How can you identify citalopram or escitalopram

Locate the ring and see a triple === 3, also a ring + F attached to amine

Which SSRI doesn’t follow the Phenoxy part and is rather just a phenylalkylamine

Sertraline

1) What drug is it

2) How can you tell what drug it is

3) NET or SERT activity? How can u tell?

1) Sertraline

2) How I can tell:

• No phenoxy

• On the phenyl there’s 2 chlorines attached

3) Increased SERT activity (you can’t rly tell by structure, just remember its an SSRI LOL)

WHAT CLASS OF STRUCTURES IS THIS HINTING AT

1) Is there a phenyl near an oxygen (ether)

2) Is there another phenyl ring

3) Is there a nitrogen attached to the structure somehow

SSRI structure

1) What drug is this

2) How can you tell by the structure

3) SERT or NET? How do you know

1) Duloxetine

2) Attached ring on 2,3 substituent + the thiophene ring has a S

3) Both SERT + NET!

1) How do you identify venlafaxine

2) ____ by CYP___ produces desvenlafaxine

3) How do you identify desvenlafaxine

1) Tertiary amine (N has three sticks), phenyl ring has /O\ attached

2) Dealkylation by CYP2D6

3) Instead of /O\ its HO-

1) What drug is this

2) How can you tell

3) What does the highlighted part do

4) Why is the answer to #3 important

5) What kind of metabolism does this structure undergo (2 types)

1) Bupropion

2) Cause of the t-butyl

3) Acts as a shield to stop MAO from dealkylating (chopping parts off)

4) B/c it prevents bupropion from turning into breakdown products that act like stimulants or appetite suppressants

5). Hydroxylate (Cyp2B6) , Reduction

1) What structure is this

2) SERT or NET activity

3) Metabolism? (2?)

1) Fluoxetine

2) SERT because of substitution on #4

3) N/A

1) What structure is this

2) SERT or NET activity

3) Metabolism? (2?)

1) Atomoxetine

2) NET, because of substitution on 2

3) Hydroxylation + Dealkylation

1) What kind of structure does this represent

2) Have more NET or SERT activity? How do you know?

3) Does this have more or less anticholinergic side effects

1) Secondary TCA’s (Nortriptyline, Amoxapine, Desipramine)

2) NET —> Secondary amine

3) Less anticholinrgeric effect

1) What kind of drug is this

2) More NET or SERT activity? How do you know?

3) More or less anticholinergic side effects?

1) Tertiary TCAs (Amitriptyline, Clomipramine, Doxepine)

2) SERT, tertiary amine

3) More anticholinergic side effects

How do you go from a tertiary TCA to a secondary TCA

Dealkylation via CYP2D6

WHAT KIND OF STRUCTURE IS THIS

1) 6-7-6 ring arrangement

2) A 3-carbon side chain that bears (3)

3) A terminal amino group

TCAs

When interpreting ratios, a lower number =

Higher affinity

When interpreting NET/SERT ratio, lower number means

> NET affinity

When interpreting NET/SERT ratio, a higher number means

More SERT affinity

Lisdexamfetamine is a ___ drug. The second half is what amino acid

Pro-drug; Lysine

1) What drug is this

2) How can you tell

3) Which one possesses anti-ADHD activity

4) How to remember ^

5) What drug class (hint: don’t say stimulant)

1) Methylphenidate

2) Looks like a person squatting and stretching (I do more yoga on stimulants)

3) Bottom

4) Torso is THICK

5) NDRI