Expressing both mania and depression

Treated wuth Litium

Depressed mood

Guilt

Anxiety

Insomnia

Fatigue

Anorexia

Over-excitement/activity

Elation

Delusion of grandeur

Irritability

Aggressive behaviour

Monoamine Hypothesis

Depression caused by the deficiency of one or more 3 catecholamine (serotonin, epinephrine, dopamine)

Mechanism of antidepressant

1)         Increase levels of one or more catecholamine

2)         Blocks reuptake or inhibits its destruction by MAO

Problems with monoamine hypothesis

1) Some drugs that increase neurotransmitters have no antidepressant effect

2) Long delay between rise in neurotransmitters and clinical effect

3) Decrease of neurotransmitters causes only a few types of depression

Serotonin

5-hydroxytryptamine (5HT)

Imbalance causes depression

Where is serotonin found?

CNS

Blood vessels

Smooth muscles

Platelets

GI tract

Monoamine Inhibitor (MAOi)

Increases neurotransmitter in the synapse by blocking destruction by MAO

Non-selective, irreversible (makes it long lasting)

Severe interaction with food and drugs

MAO A and MAO B

Tyramine

MAOi

Mixed with food and drugs can dangerously increase BP

Meperidine

MAOi

Causes fever

What happens when MAOi is mixed with cheese?

Increases the NE levels causing the increase of blood pressure to dangerous levels

MAO A

MAOi

Metabolises MAO linked to depression (NA, 5HT)

Moclobemide

MAO A

Reversibly binds to MAO

Solves side effect of Tyramine

MAO B

Treats Parkinson`s

Metabolizes DA and protoxins

Tricyclic Antidepressants (TCA)

Also an antipsychotic

Blocks reuptake pump of NA, 5HT and DA

Has many functional group on its surface

α1 adrenergic antagonist

Histamine-1 antagonist

Muscarinic antagonist

Side effects of histamine-1 antagonism?

Weight gain

Drowsiness

Side effect of muscarinic antagonism?

Constipation

Blurred vision

Dry mouth

Drowsiness

Anti-SLUDGE+

Side effect of α1 adrenergic antagonism?

Dizziness

Drowsiness

Decrease BP

Serotonin Selective Reuptake Inhibitors (SSRI)

Better than TCA (no side effects)

Specifically blocks the reuptake of 5HT

Safer in case of overdose

Side effects: anorexia, insomnia, sexual dysfunction, anxiety, (suicide?)

What happens when there is a low concentration of 5HT at the dendritic end of the neuron?

Depression due to low number of signals being sent down the axon to release more 5HT into the synapse

How does an antidepressant drug solve low concentration of 5HT?

Inhibits the reuptake of 5HT at both the dendritic and at the axon

What happens when the autoreceptors on the on the dendrites desensitizes due to 5HT?

Downregulation of autoreceptors to release more 5HT at the axon

What happens when the presynaptic inhibitory (negative feedback) receptors downregulate?

Increases the release of 5HT into synapse

Paroxetine (Paxil)

SSRI Antidepressant

Increases 5HT in the synapse

Sertaline (Zoloft)

SSRI antidepressant

Increases 5HT in synapse

Citalopram

SSRI antidepressant

Increases 5HT in the synapse

Safer in case of overdose

NA/DA Reuptake inhibitor

Buproprion

Increases NA/DA levels

Used to help stop smoking

Does not affect 5HT

Buproprion

NA/DA Reuptake Inhibitor

Increases NA/DA level

Used to help stop smoking

Does not affect 5HT

Serotonin-NA Reuptake Inhibitor (SNRI)

Venlafaxine (effexor)

Inhibits reuptake of 5HT, NA, DA

Varies according to dose (5HT à NA à DA)

More rapid affect

Side effects: nausea, anorexia, dizziness, parenthesia, sexual dysfunction, agitation

Parenthesia

Tingling feeling

Venlafaxine (Effexor)

SNRI

Inhibits reuptake of 5HT, NA, DA

Rapid response

NA/5HT Specific Antagonist

Mirtazapine

α2 antagonist

Increases release of NA/5HT

Aka: 5HT & NE disinhibitors (SNDI)

Mirtazapine

NA/5HT Specific antagonist

α2 antagonist

Increases release of NA/5HT

Aka: SNDI

What drug blocks 5HT1A receptor and what side effects are associated with this receptor?

Mirtazapine (NA/5HT specific Antagonist)

Improved cognition

No anxiolytic and no antidepressant

What drug blocks 5HT2A receptor and what side effects are associated with this receptor?

Mirtazapine (NA/5HT specific Antagonist)

Sleep restoring

No anxiolytic, no antidepressant, no sexual dysfunction

What drug blocks 5HT2C receptor and what side effects are associated with this receptor

Mirtazapine (NA/5HT specific Antagonist)

Weight gain

No anxiolytic and no antidepressant

What drug blocks 5HT3 receptor and what side effects are associated with this receptor

Mirtazapine (NA/5HT specific Antagonist)

No GI problem and no nausea

Serotonin-2 Antagonist/Reuptake Inhibitors (SARI)

Trazadone

Sedative

Increases 5HT

Blocks 5HT-2 receptors that are responsible for side effects

Electroconvulsive Therapy (ECT)

Patient lightly anaesthetized, ventilated and paralyzed with neuromuscular blockers then electrical currents are applied

For severe depression

Side effect: confusion, memory loss

Lithium

Mood stabilizer

Treats manic depression (bipolar)

Enters via Na⁺ channel

Inhibits the production from IP2àIP1 & IP1à free inositol

Inhibits phosphatidylinositol signal cascade in the brain

Long half life

Narrow therapeutic window

Side effects: nausea, tremors, polyuria & thirst