Mechanism Action of Drugs

Mechanism Action of Antidepressants

Anti-depressants are a class of drugs commonly used in the treatment of depressive
disorders. They work by targeting specific neurotransmitters in the brain to alleviate
symptoms of depression. Here is an overview of the mechanisms of action of antidepressants:

1. Selective Serotonin Reuptake Inhibitors (SSRIs):

SSRIs, such as fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro),

are the most commonly prescribed antidepressants. They work by selectively inhibiting the
reuptake of serotonin, a neurotransmitter involved in mood regulation. By blocking the
reuptake of serotonin, SSRIs increase the concentration of serotonin in the brain, leading to
improved mood and reduced depressive symptoms.

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):

SNRIs, such as venlafaxine (Effexor) and duloxetine (Cymbalta), target both

serotonin and norepinephrine neurotransmitters. Similar to SSRIs, SNRIs inhibit the reuptake
of these neurotransmitters, resulting in increased levels of serotonin and norepinephrine in the
brain. The elevated levels of these neurotransmitters help regulate mood, reduce depression,
and improve overall well-being.

3. Tricyclic Antidepressants (TCAs):

TCAs, such as amitriptyline and nortriptyline, are older antidepressants that also work
by inhibiting the reuptake of serotonin and norepinephrine. However, TCAs have a broader
mechanism of action, affecting other neurotransmitter systems as well. By increasing the
availability of these neurotransmitters, TCAs help regulate mood and alleviate depressive
symptoms.

4. Monoamine Oxidase Inhibitors (MAOIs):

MAOIs, such as phenelzine and tranylcypromine, work by inhibiting the enzyme

monoamine oxidase, which breaks down serotonin, norepinephrine, and dopamine in the
brain. By inhibiting this enzyme, MAOIs increase the levels of these neurotransmitters,
leading to improved mood and relief from depression. However, MAOIs have significant
dietary and drug interaction restrictions, making them less commonly prescribed as first-line
treatments.

5. Atypical Antidepressants:

Atypical antidepressants include various medications that do not fit into the previous
categories but are effective in treating depression. For example, bupropion (Wellbutrin)
inhibits the reuptake of dopamine and norepinephrine, while mirtazapine (Remeron)
enhances the release of both norepinephrine and serotonin. These medications have unique
mechanisms of action that contribute to their antidepressant effects.

The neurochemical imbalances associated with depression are complex, and different
individuals may respond differently to various antidepressants. Moreover, the therapeutic
effects of antidepressants often take time to manifest, as changes in neurotransmitter levels
gradually occur and normalize over several. Antidepressants work through various
mechanisms of action to regulate neurotransmitters involved in mood regulation, such as
serotonin, norepinephrine, and dopamine. By increasing the availability of these
neurotransmitters, antidepressants help alleviate depressive symptoms and improve overall
well-being.

Mechanisms of Action of Anxiolytics

Anxiolytics, also known as anti-anxiety medications, are prescribed to treat various

anxiety disorders and related conditions. They work by targeting specific neurotransmitters in
the brain to reduce excessive anxiety and promote a sense of calm. Mechanisms of action of
anxiolytics is following:

1. Benzodiazepines:

Benzodiazepines, such as diazepam (Valium), alprazolam (Xanax), and lorazepam

(Ativan), are commonly prescribed anxiolytics. They enhance the effects of gamma-
aminobutyric acid (GABA), a neurotransmitter that inhibits brain activity. Benzodiazepines
bind to specific receptors on GABA receptors, increasing the inhibitory actions of GABA.
This results in a reduction of excessive neuronal firing and a calming effect on the central
nervous system, alleviating anxiety symptoms.

2. Selective Serotonin Reuptake Inhibitors (SSRIs):

 While SSRIs are primarily known as antidepressants, they are also effective in
treating certain anxiety disorders, such as generalized anxiety disorder (GAD) and obsessive-
compulsive disorder (OCD). SSRIs work by increasing the availability of serotonin, a
neurotransmitter involved in mood regulation. By selectively inhibiting the reuptake of
serotonin, SSRIs increase serotonin levels in the brain, which helps modulate anxiety and
reduce symptoms associated with anxiety disorders.

3. Azapirones:

Azapirones, such as buspirone (Buspar), are a class of anxiolytics that work by acting
as partial agonists at serotonin 5-HT1A receptors. By binding to these receptors, azapirones
increase serotonin activity in specific brain regions, which helps regulate anxiety levels. The
exact mechanism of action of azapirones is not fully understood, but their effects are believed
to involve serotonin and other neurotransmitter systems.

4. Beta-Blockers:

Beta-blockers, such as propranolol, are primarily used to treat cardiovascular

conditions but can also be prescribed for situational anxiety, such as performance anxiety or
social anxiety. Beta-blockers work by blocking the effects of adrenaline and noradrenaline on
beta-adrenergic receptors. By reducing the physical symptoms of anxiety, such as rapid
heartbeat and trembling, beta-blockers can help individuals feel less anxious in anxiety-
provoking situations.

Anxiolytics are typically prescribed for short-term use due to the potential for
dependency and tolerance with long-term use. Individual responses to anxiolytics may vary,
and the choice of medication is based on the specific anxiety disorder, the severity of
symptoms, and the patient's overall health.

Mechanisms of Action of Antipsychotics

Antipsychotic medications, also known as neuroleptics, are commonly used in the

treatment of psychotic disorders such as schizophrenia and bipolar disorder. They work by
targeting specific neurotransmitter systems in the brain to reduce psychotic symptoms and
stabilize mood. Mechanisms of action of antipsychotics is following:

1. Typical Antipsychotics:
 Typical antipsychotics, also referred to as first-generation antipsychotics, include
medications such as haloperidol and chlorpromazine. These medications primarily block
dopamine D2 receptors in the brain. By antagonizing these receptors, typical antipsychotics
reduce the activity of dopamine, which is believed to contribute to psychotic symptoms. The
blockade of D2 receptors also affects other neurotransmitter systems, such as serotonin and
norepinephrine, which may contribute to the overall therapeutic effects.

2. Atypical Antipsychotics:

Atypical antipsychotics, also known as second-generation antipsychotics, include

medications such as risperidone, olanzapine, and quetiapine. These medications have a
broader mechanism of action compared to typical antipsychotics. Atypical antipsychotics also
antagonize dopamine D2 receptors, but they have a higher affinity for serotonin 5-HT2A
receptors. By blocking these receptors, atypical antipsychotics help regulate both dopamine
and serotonin neurotransmission. This dual action is thought to improve the positive and
negative symptoms of psychosis, as well as mood stabilization in bipolar disorder.

3. Other Neurotransmitter Systems:

Antipsychotics can also affect other neurotransmitter systems in the brain,

contributing to their therapeutic effects. For example, atypical antipsychotics have varying
affinities for other serotonin receptors, such as 5-HT1A and 5-HT2C. Activation of 5-HT1A
receptors may contribute to the anxiolytic and antidepressant effects of some atypical
antipsychotics, while blockade of 5-HT2C receptors may help improve cognitive function.

Psychotic disorders involve complex neurochemical imbalances, and the interplay

between various neurotransmitters is involved in the manifestation of symptoms.
Antipsychotics help restore the balance of neurotransmitters, particularly dopamine and
serotonin, in specific brain regions associated with psychosis.Additionally, antipsychotics are
classified into different generations based on their side effect profiles. Typical antipsychotics
are more likely to cause extrapyramidal side effects such as muscle stiffness and tremors,
while atypical antipsychotics have a lower risk of these side effects but may be associated
with metabolic side effects such as weight gain and increased risk of diabetes.

Mechanisms of Action of Mood Stabilizers

 Mood stabilizers are a class of medications primarily used in the treatment of bipolar
disorder to help stabilize mood and prevent episodes of mania or depression. While the exact
mechanisms of action are not fully understood, several mechanisms have been proposed.

1. Ion Channel Modulation:

One proposed mechanism for mood stabilizers involves the modulation of ion
channels in the brain. For example, lithium, one of the oldest and most commonly used mood
stabilizers, is thought to affect multiple ion channels, including sodium, potassium, and
calcium channels. These effects may help regulate neuronal excitability and neurotransmitter
release, contributing to mood stabilization.

2. Neurotransmitter Modulation:

Mood stabilizers may also impact the balance of neurotransmitters in the brain. For
example, lithium has been shown to modify the release, synthesis, and reuptake of various
neurotransmitters, including serotonin, norepinephrine, and dopamine. By modulating these
neurotransmitter systems, mood stabilizers can help regulate mood and reduce the severity of
mood episodes.

3. Neuroprotective Effects:

Some mood stabilizers, such as lithium and certain anticonvulsant medications like
valproate and lamotrigine, have been suggested to possess neuroprotective properties. They
may enhance cellular resilience and protect against neurotoxicity, which could play a role in
preventing mood episode recurrence and stabilizing mood.

4. Second Messenger Systems:

Several mood stabilizers have been found to affect second messenger systems in the
brain, such as the cyclic adenosine monophosphate (cAMP) and inositol signaling pathways.
For instance, lithium may inhibit the enzyme glycogen synthase kinase-3 (GSK-3), which is
involved in these signaling pathways. Modulation of these systems can impact intracellular
signaling and gene expression, potentially contributing to the stabilization of mood.

Mechanisms of action of mood stabilizers can vary depending on the specific

medication. For example, lithium is a unique mood stabilizer with a broad range of effects,
while anticonvulsant medications like valproate, lamotrigine, and carbamazepine have their
own specific mechanisms.
Mechanisms of Action of Stimulants

Stimulants are a class of medications that are primarily used to treat attention deficit
hyperactivity disorder (ADHD). They work by increasing the activity of certain
neurotransmitters in the brain, which helps improve attention, focus, and impulse control.

1. Dopamine and Norepinephrine Reuptake Inhibition:

The primary mechanism of action of stimulants involves the inhibition of dopamine

and norepinephrine reuptake. Medications such as methylphenidate (Ritalin) and
amphetamine-based drugs (e.g., Adderall) block the reuptake transporters responsible for
removing dopamine and norepinephrine from the synaptic cleft. By inhibiting reuptake,
stimulants increase the levels of these neurotransmitters, which enhances their signaling and
availability in specific brain regions involved in attention and impulse control.

2. Dopamine and Norepinephrine Release:

In addition to reuptake inhibition, stimulants also promote the release of dopamine

and norepinephrine from presynaptic nerve terminals. By increasing the release of these
neurotransmitters, stimulants further amplify their effects and enhance neurotransmission in
the relevant brain circuits associated with attention and impulse control.

3. Modulation of Prefrontal Cortex Function:

The prefrontal cortex is a brain region involved in executive functions, including

attention, working memory, and impulse control. Stimulants have been found to enhance
prefrontal cortex activity and improve the function of these cognitive processes. By
increasing dopamine and norepinephrine levels in the prefrontal cortex, stimulants help
optimize the functioning of this brain region, leading to improved attention and cognitive
control.

4. Effects on Other Neurotransmitters:

While the primary focus is on dopamine and norepinephrine, stimulants can also
affect other neurotransmitters to some extent. For example, they may influence serotonin
levels, although the exact mechanisms and significance of these effects are not fully
understood. These additional actions may contribute to the overall therapeutic effects of
stimulants.
 Stimulants exert their therapeutic effects by increasing the levels of dopamine and
norepinephrine in the brain through reuptake inhibition and increased release. These actions
enhance neurotransmission in brain circuits related to attention and impulse control, leading
to improved focus, attention, and behavioral control in individuals with ADHD.