Atypical antidepressants

Atypical antidepressants are mainly used to treat major depressive disorder. This disorder causes a persistent feeling of sadness and loss of interest in everyday activities. Even though the exact cause of depression is still unknown, there's some evidence that suggests it’s related to low levels of neurotransmitters like serotonin, norepinephrine, and dopamine. Typical antidepressants like selective serotonin reuptake inhibitors or tricyclic antidepressants work by increasing the levels of serotonin and norepinephrine, while atypical antidepressants often have multiple mechanisms of action.

All right, now within the brain, there are many different types of neurons, but we’re going to focus only on three: serotonergic neurons, which produce serotonin; noradrenergic neurons, which produce norepinephrine; and dopaminergic neurons, which produce dopamine. Each of these neurons synthesizes and stores their neurotransmitters in small vesicles. So, when an action potential reaches the presynaptic membrane, these vesicles fuse with the membrane, releasing neurotransmitters into the synaptic cleft. Once released, serotonin (or 5-HT) binds to 5-HT2 receptors on the postsynaptic membrane, thereby increasing neural stimulation, and regulating mood, feeding, and reproductive behavior. On the other hand, norepinephrine binds to norepinephrine receptors on the postsynaptic membrane, boosting alertness. And finally, dopamine binds to dopamine receptors, thereby stimulating cognitive functions, motivation, and awakeness.

As long as there’s a high enough concentration of neurotransmitters in the synaptic cleft, the postsynaptic neurons will continue to fire. Now, serotonergic neurons on their presynaptic membrane have serotonin transporters (or SERT); noradrenergic neurons have norepinephrine transporters (or NET); while dopaminergic neurons have dopamine transporters (or DAT). These membrane proteins transport neurotransmitters from the synaptic cleft back into presynaptic neurons. This leads to a decreased neurotransmitter concentration within the synaptic cleft, causing the postsynaptic neurons to stop firing. Noradrenergic and serotonergic neurons are also rich in alpha 2 receptors. When stimulated, alpha 2 receptors inhibit the activity of the presynaptic neurons and decrease the release of norepinephrine or serotonin.