Antidepressants med chem

What is Major Depression Disorder

Symptoms interfere with abiliity to work, study, sleep, eat and enjoy

What is Dysthymia

Mild chronic depression, improper functioning and not feeling good about self

What is bipolar disorder

Cause monamine signalling and HPA axis disruption

What is seasonal affective disorder

Less common type of depression

What is Monamine Hypothesis

Deficiency in 5-HT, NE and DA

What is cholinergic theory of depression

Balance between cholinergic and adrenergic systems is disrupted.

Hypercholinerhic action at neuronal nAChR leads to depressio

What is Hormonal Hypothesis

Hyperactivity of hypothalamus-pituatary adrenal axis influences levels of Ach release

nAChR hypercholinergic response leads to depression

What family do Monamine reuptake transporters belong to

Na/Cl dependent NT transporters

What is the structure of Monamine reuptake transporters

Intrinsic membrane proteins with 12 TM helices

What is the role of Monamine Transporterrs

Transport DA, NE and 5HT

What powers neurotransmitter uptake

Sodium gradient

What is the structure of Tricyclic Antidepressants

Contain 6-7 ring arrangement

Less rigid than phenothiazines

Side chain attached to Central ring and have 3 C atoms

3-Cl= enhanced affinity

Why are TCAs rigid

Ethylene bridge causes 2 phenyl rings to be twisted out of the plane

What is the MOA of TCAs

Selective inhibitor of NE reuptake Transporter which increases NE concentration of the synaptic cleft

What are Serotinin and Norepinephrine Reputake Inhibitors

Inhibit both serotonin and Norepinephrine

Bind to neuroreceptors leading to low therapeutic index

Which drugs are Tricylcic secondary amine antidepressants

Desimipramine

Nortriptilyine

Which drugs are Tertiary Tricyclic Amine Antidepressants

Imipramine

Amitriptyline

Doxepin

Clomipramine

What do SSRIs have a high affinity for

Serotonin

True or False Zimedine is a selective inhibitor of 5HT repuptake

True

How is Zimidine related to Amitriptyline

Open chain analog of amitrip

Which SSRIs are Phenoxyphenylalkamines

Fluoxetine

paroxetine

Which SSRIs are Phenylalkylamines

Citalopram

Escitalopram

Sertraline

Fluvoxamine

What is the SAR of Fluoxetine

Phenoxy at 3 position

CF3 increases selectivity for SERT

Cannot be disubstituted at 2,4 or 3,4

What happens if Fluoxetine becomes a semi rigid analog

Maintains selectivity but reduces potency

How is Paroxetine related to Fluoxetine

Paroxetine is a constrained analog where there is a piperidine ring S

SAR of Paroxetine

Methylation of piperidine ring= less potent

Dont replace F

Dont replace methylenedioxy with OCH3

How is Paroxetine metabolized

By CYP2D6 then methylated/glucoronidated and excreted in urine

SAR of Citalopram and Escitalopram

Phenylispiro-isobenzofuran with 5 cyano and 4 fluoro

S enantiomer

Selective for SERT

SAR of Sertraline

Phenylaminotetralin derivative

Derived from Tametraline

3,4 di Cl

SAR of Fluvoxamine

Nontricyclic SERT inhibitor

E isomer active

4CF2 or e withdrawing group needed

Which drugs are Nontricyclic SNRIs

Venlafaxine

Desvenlafaxine

Milnacipran

Levomilnacipran

Duloxetine

What is the SAR of Venlafaxine

Synthetic derivative of Phenethylamine

Open chain analog of TCA
high affinity for Sert

What is Desvenlafaxine

5GT and NE reuptake inhibitor SNRI

More potent for SERT

OH vs OCH3 on Venlafaxine

What is Milnacipran and Levomilnacipran

Cis amino methal substituted phenylcyclopropane carboxamide

Inhibits 5HT- and NE reuptake

Competitive inhibitor in CNS

Cyclopropyl ring conformationally restricts the pendant tertiary carboxamide and primary amine groups

What is Duloxetine

isostere of fluoxetine

5HT and NE reuptake inhibition

What is Duloxetine metabolized bt

N desmethylation

4-hydroxylation

What is Bupropion

FOR MDD

Weak inhibitor of reuptake of DA and NE

Antagonist of nAChR so can be used for smokin cessation aid

What does Bupropopion not produce

Sympathomimetic CNS stimulant amine metabolite

What is Trazodone

Dose dependent

5-HT2A anatagonist and weak 5-HT reuptake at presynaptic neuronal membrane

True or false we want activation of 5HT1A and Inhibitoin of 5-HT2a to treat depression

True

What is the MOA of Vilazodone

5-HT1A partial agonist with strong inhibition of SERT

MOA of Vortexetine

Inhibits SERT

Agonist at 5HT1A

What is Mirtazapine

Atypical Antidepressant SSA

What is the MOA of Miratazpine

Blocks presynaptic a2 receptor facilitating release of 5-HT

Antagonizes 5HT2 and 3

MOA of Ketamine

NMDA antagonist to decrease channel opening frequancy

Allosteric mechanism

MOA of MAO inhibitors

Block breakdown of NE, 5-HT and DA

Blocks breakdown of tyramine

Which drugs are MAO Inhibitors

Ipronizad

isonizad

Phenlzine

MOA of Phenelzine

Nonselective irrevesible MAO Inhib

MOA of Trancylcypromine

NONselective irreversible MAOI

Which drug is a mood stabalizer used first line for bipolar

LIthium SaltsM

MOA of Lithium Carb

Inhibition IP3/DAG pathway

Which drugs are Anticonvulsants

Carbamazepine

Oxcarbazepine

Valproic acid

Lamotrigine