TCAs increase neurotransmitter levels by preventing nerve endings — called synapses — from drawing these chemicals back into their tissues, which is normally how the body reduces their concentrations. They increase levels of norepinephrine and serotonin, two neurotransmitters, and block the action of acetylcholine, another neurotransmitter, this helps nerve signalling in the brain, which can help relieve depression. Tricyclic antidepressants are most effective for people with severe depression compared with those with mild to moderate depression, but they are also given as alternatives to SSRIs (selective serotonin re-uptake inhibitors) and are sometimes used in panic disorder, obsessive compulsive disorder and the treatment of chronic pain.

1. Tricyclic Antidepressants
By:
Noorulain Wajid

2. Biogenic amine hypothesis (depression):
It proposes that,
“Depression is due to deficiency of biogenic amines such as
norepinephrine and serotonin at certain key sites in brain.”
Tricyclic antidepressants (TCAs):
The tricyclic antidepressants block the absorption (reuptake) of
the neurotransmitters serotonin and norepinephrine into the
presynaptic neuron by blocking norepinephrine and serotonin
reuptake receptors and alpha2 receptors on presynaptic
neuronal membrane. Thus, increasing the levels of these two
neurotransmitters in the synaptic cleft and resulting in
antidepressant effects.

3. TCAs include:
Tertiary amines
› Imipramine (prototype drug)
› Amitriptyline
› Clomipramine
› Doxepin
› Trimipramine
Secondary amines
› Desipramine
› Nortriptyline
› Amoxapine
› Maprotiline
› Protriptyline

4. Mechanism of action:
› When there is low norepinephrine and serotonin in neuron or
synaptic cleft, TCAs start blocking serotonergic, alpha2
adrenergic, histaminic and muscarinic receptors. Resulting in
increase level of neurotransmitter in synaptic cleft.
› They possess antimuscarinic actions.
Actions:
› TCAs elevate mood, improve mental alertness, increase
physical activity and reduce 50% to 70% of depression in
individuals with major depression.

5. TCAs
Mechanism
Of Action

6. Clinical
uses
Depression
Enuresis
Chronic
pain
Obsessive
compulsive
disorder
Cataplexy
Attention
deficit
disorder in
children
Panic
attacks
School
phobia

7. Pharmacokinetics:
› TCAs are well absorbed orally because of their lipophilic
nature.
› Widely distributed, readily penetrate into CNS and undergo
extensive hepatic metabolism before elimination.
› TCAs have longer half-life of 8-36 hours so permit once daily
dosing.

8. Adverse effects:
Blockade of
muscarinic
receptor
Blurred vision
Dry mouth
Urinary
retention
Constipation
Aggravation of
glaucoma and
epilepsy
Increased
catecholamine
activity
Arrhythmia
Cardiomyopathies
Blockade of
alpha-
adrenergic
receptor
Orthostatic
hypotension
Tachycardia
Blockade of
histamine
receptor
Sedation
Others
Tremors
Sexual
disturbances
Jaundice
Hemolytic
anemia
Confusion

9. Precautions:
› Should be used with caution in maniac-depressive patients.
› TCAs have narrow therapeutic index; 5-6 times maximal daily
dose can be lethal.
› Should be given in limited quantities to those depressed,
suicidal in nature patients and be monitored closely.