How Lyrica 75 mg Works: Mechanism of Action and Clinical Applications

Lyrica, with the active ingredient pregabalin, is a widely used medication for the treatment of various neurological and pain-related conditions. Available in multiple dosages, Lyrica 75 mg is a commonly prescribed strength. This article explores how Lyrica 75 mg works, its mechanism of action, and its clinical applications.

Mechanism of Action

Lyrica (pregabalin) is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA), but it does not directly bind to GABA or benzodiazepine receptors. Instead, pregabalin binds to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding reduces the release of several neurotransmitters, including glutamate, norepinephrine, substance P, and calcitonin gene-related peptide (CGRP). By modulating the release of these excitatory neurotransmitters, pregabalin helps to stabilize neuronal hyperactivity, which is a common feature in various neurological disorders.


Pregabalin is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1 hour. It has a high bioavailability of approximately 90% and does not bind significantly to plasma proteins. Pregabalin is not extensively metabolized and is primarily excreted unchanged in the urine. Its half-life is about 6.3 hours, allowing for twice-daily or three-times-daily dosing.

Clinical Applications
Lyrica 75 mg is approved for several clinical applications, primarily related to its ability to modulate neurotransmitter release and stabilize neuronal activity. These include:

Neuropathic Pain:

Diabetic Peripheral Neuropathy (DPN): Lyrica 75 mg is effective in reducing pain associated with diabetic neuropathy. Diabetic neuropathy results from nerve damage due to prolonged high blood sugar levels, causing burning, tingling, or stabbing pain in the extremities.
Postherpetic Neuralgia (PHN): This condition occurs following an outbreak of herpes zoster (shingles) and is characterized by severe pain in the areas affected by the rash. Lyrica 75 mg helps reduce the persistent pain associated with PHN.

Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and tenderness in localized areas. Lyrica 75 mg helps alleviate the pain and improves the quality of life for fibromyalgia patients. It is believed to reduce the excessive neuronal firing in the brain that is associated with fibromyalgia.

Partial-Onset Seizures: Lyrica 75 mg is used as an adjunctive therapy for adults with partial-onset seizures. By reducing the release of excitatory neurotransmitters, pregabalin helps to decrease the frequency of seizures.
Generalized Anxiety Disorder (GAD):

Lyrica 75 mg is also effective in treating generalized anxiety disorder. It reduces the symptoms of anxiety by stabilizing hyperactive neuronal circuits involved in anxiety.
Mechanism of Action in Specific Conditions
Neuropathic Pain:

In conditions like diabetic peripheral neuropathy and postherpetic neuralgia, damaged nerves send abnormal signals to the brain, resulting in chronic pain. Pregabalin’s ability to bind to the alpha-2-delta subunit of voltage-gated calcium channels reduces the influx of calcium into neurons. This reduction in calcium entry decreases the release of pain-related neurotransmitters, thereby diminishing the sensation of pain.


Fibromyalgia involves widespread pain, which may be due to abnormal sensory processing in the central nervous system. Pregabalin’s modulation of neurotransmitter release helps to reduce the abnormal neuronal firing and hyperactivity in the brain. This action leads to a reduction in the pain and fatigue associated with fibromyalgia, thus improving patient outcomes.


In epilepsy, particularly partial-onset seizures, there is abnormal and excessive neuronal activity in the brain. By inhibiting the release of excitatory neurotransmitters, pregabalin helps to stabilize the neuronal activity and reduce the frequency of seizures.

Generalized Anxiety Disorder:

For GAD, the exact mechanism by which pregabalin exerts its anxiolytic effects is not fully understood. However, it is believed that its ability to decrease the release of excitatory neurotransmitters plays a crucial role. This action helps to stabilize hyperactive circuits in the brain that are involved in anxiety, thus reducing symptoms of anxiety.

Efficacy and Safety
Clinical Trials:

Numerous clinical trials have demonstrated the efficacy of Lyrica 75 mg in its approved indications. For instance, in diabetic peripheral neuropathy and postherpetic neuralgia, pregabalin significantly reduced pain scores compared to placebo. In fibromyalgia, patients treated with pregabalin reported significant improvements in pain, sleep quality, and overall quality of life. For epilepsy, clinical trials have shown that pregabalin effectively reduces the frequency of partial-onset seizures when used as an adjunctive therapy.

Adverse Effects:

While Lyrica 75 mg is generally well-tolerated, it can cause side effects. The most common adverse effects include dizziness, somnolence, dry mouth, peripheral edema, blurred vision, weight gain, and difficulty with concentration or attention. These side effects are usually mild to moderate and tend to diminish with continued use. However, in some cases, they may necessitate discontinuation of the medication.

Drug Interactions:

Pregabalin does not significantly interact with other medications, as it is not extensively metabolized and is excreted unchanged in the urine. However, caution is advised when using pregabalin with other central nervous system depressants, as it may enhance the sedative effects.

Patient Considerations
Dosing and Administration:

Lyrica 75 mg is typically taken two to three times daily, with or without food. The dosing regimen may be adjusted based on individual patient response and tolerability. It is important for patients to follow their healthcare provider’s instructions and not to abruptly discontinue the medication, as this can lead to withdrawal symptoms.

Special Populations:

Renal Impairment: Since pregabalin is excreted primarily by the kidneys, dose adjustments are necessary for patients with renal impairment.
Elderly Patients: Elderly patients may be more susceptible to the side effects of pregabalin, particularly dizziness and sedation. Careful dose titration is recommended in this population.
Pregnancy and Lactation: Pregabalin is classified as a Category C drug for pregnancy, indicating that risk to the fetus cannot be ruled out. It should only be used if the potential benefits justify the potential risk to the fetus. Pregabalin is also excreted in breast milk, and a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Lyrica 75 mg (pregabalin) is a versatile medication that plays a significant role in the management of several neurological and pain-related conditions. Its ability to modulate neurotransmitter release and stabilize neuronal activity makes it effective in treating neuropathic pain, fibromyalgia, partial-onset seizures, and generalized anxiety disorder. The medication’s well-documented efficacy, coupled with its generally favorable safety profile, underscores its value in clinical practice.

Patients and healthcare providers should work together to optimize treatment outcomes, considering factors such as dosing, potential side effects, and individual patient needs. With appropriate use, Lyrica 75 mg can significantly improve the quality of life for individuals suffering from these debilitating conditions

How Lyrica 75 mg Works: Mechanism of Action and Clinical Applications