Adrenergic antagonist drug

 

Antidepressant drugs target mainly norepinephrine and serotonin neurotransmitters, which are thought to be mainly related to depression (those drugs increase the concentration of these neurotransmitters by inhibiting their degradation and/or reuptake from the synaptic cleft).

Antidepressant drug classes

1. Tricyclic antidepressants (TCAs).
2. Serotonin/norepinephrine reuptake inhibitors (SNRIs).
3. Selective serotonin reuptake inhibitors (SSRIs).
4. Selective norepinephrine reuptake inhibitors.
5. Mono amine oxidase (MAO) inhibitors.

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants (TCAs) drug list:

• Amitriptyline.
• Nortriptyline.
• Clomipramine.
• Imipramine.
• Desipramine.
• Doxepin.
• Maprotiline.

Mechanism of action of TCAs

They provide their action by blocking the reuptake of serotonin and norepinephrine into presynaptic nerve terminals, which leads to increase the concentration of these neurotransmitters in the synaptic cleft.

Adverse effects of TCAs

The adverse effects of tricyclic antidepressants (TCAs) are related to its alpha 1, histamine ,muscarinic, 5-HT receptors blocking effects.

• Sedation.
• Weight gain.
• Atropine-like effects.
• Postural hypotension.
• Reflex tachycardia.
• Sexual dysfunction.
• Seizures (TCAs lower seizures threshold).

Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) drug list:

• Fluoxetine.
• Paroxetine.
• Citalopram.
• Escitalopram.
• Sertraline.
• Fluvoxamine.

Mechanism of action of SSRIs

They exert action by inhibiting the reuptake of serotonin, thereby increasing serotonin concentration at the synaptic cleft, thus increase serotonin activity.

 

Pharmacokinetics of SSRIs

• SSRIs are well absorbed after oral administration and they have a peak effect after 3-8 hours.
• Sertraline absorption may slightly increase with food.
• Most SSRIs are highly bound to plasma protein with the exception of escitalopram is less bounded to plasma proteins.
• All SSRIs are metabolized by CYP 450 enzymes in the liver.
• The excretion of SSRIs occurs mainly via metabolism in the liver.
• Fluoxetine and fluvoxamine metabolites are excreted predominantly in the urine, while sertraline and paroxetine metabolites are excreted in the feces.

Adverse effects of SSRIs

• Sleeping disturbances.
• Sexual dysfunction.
• SSRI withdrawal syndrome ( which characterized by headache, agitation, flu-like symptoms, changes in sleep pattern).
• Suicidal attempts especially in children and teenagers.

Serotonin/norepinephrine reuptake inhibitors (SNRIs)

Serotonin/norepinephrine reuptake inhibitors (SNRIs) drug list:

• Duloxetine.
• Venlafaxine.

Mechanism of action of SNRIs

They act by inhibiting the reuptake of norepinephrine and serotonin into presynaptic nerve terminals, resulting in increased concentration of those neurotransmitters in the synaptic cleft.

Pharmacokinetics of SNRIs

• Duloxetine is metabolized in the liver by CYP 450 (CYP 2D6 & CYP 1A2 isoenzymes), and its metabolites are inactive.
• Venlafaxine is metabolized in the liver by CYP 450 (CYP2D6, CYP3A3 & CYP3A4), and its metabolite desvenlafaxine is also active.
• The half-life of duloxetine is approximately 12 hours.
• The half-lives of Venlafaxine and its metabolite desvenlafaxine are approximately 5 hours & 11 hours respectively.
• Desvenlafaxine is partially metabolized by CYP 450 and partially conjugated, but about 50% of the drug  excreted unchanged in the urine.

Adverse effects of SNRIs

• Nausea (most common adverse effect).
• Sexual dysfunction.

Selective norepinephrine reuptake inhibitors

Selective norepinephrine reuptake inhibitors drug list:

• Reboxetine.

Mechanism of action of NRIs

They act by inhibiting of reuptake of norepinephrine in the presynaptic nerve terminals, resulting in increased concentration of norepinephrine in the synaptic cleft.

Adverse effects of NRIs

• Insomnia.
• Dizziness.
• Dry mouth.
• Constipation.
• Nausea.

Mono amine oxidase (MAO) inhibitors

Mono amine oxidase (MAO) inhibitors drug list:

Non selective MAO inhibitors

• Phenelzine.
• Isocarboxazide.
• Tranylcypromine.

Selective MAO-A inhibitors

• Chlorgyline.
• Moclobemide.

Mechanism of action of MAO inhibitors 

They act by blocking the activity of MAO enzyme, which is responsible for metabolism of norepinephrine, serotonin and dopamine, thereby increase the levels of those neurotransmitters.

Note:

1. MAO-A is responsible for metabolism of norepinephrine, serotonin and dopamine.
2. MAO-B is responsible for metabolism of dopamine only.

Adverse effects of MAO inhibitors 

• Insomnia.
• Tremors.
• Dry mouth.
• Blurred vision.
• Nausea.

References

• PubMed
• Mayoclinic
• Lippincott's Illustrated Reviews Pharmacology 5th Edition.