XILICA 50MG CAPSULE

Indications

• Neuropathic pain
• Epilepsy (partial seizures)
• Generalized anxiety disorder

Mechanism of action

Pregabalin binds presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding modulates the release of several excitatory neurotransmitters, including glutamate, substance P, norepinephrine, and calcitonin gene-related peptide. Additionally, pregabalin prevents the trafficking of the alpha2-delta subunit from the dorsal root ganglia to the spinal dorsal horn, contributing to its antiseizure and antinociceptive effects. Despite its structural similarity to GABA, pregabalin does not interact with GABA receptors, nor does it augment GABA responses or alter GABA concentrations in the brain.

Pharmacodynamics

Pregabalin exhibits analgesic and anticonvulsant properties through its action on presynaptic voltage-gated calcium channels. By inhibiting the release of excitatory neurotransmitters, pregabalin helps to stabilize neuronal excitability, providing therapeutic effects in conditions of neuropathic pain and seizures. It does not influence other neurotransmitter systems such as dopamine, serotonin, or opiate receptors, nor does it affect sodium channels or cyclooxygenase activity.

Pharmacokinetics

Pregabalin is well-absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a bioavailability of approximately 90%, which remains relatively consistent across different doses. The drug is not extensively metabolized and is primarily excreted unchanged in the urine. The elimination half-life of pregabalin is around 6 hours, which may be prolonged in patients with renal impairment. Dose adjustments are required in such cases to avoid accumulation.

Contra-indications

• Hypersensitivity to pregabalin or any of its components
• Severe renal impairment

Adverse effects

• Dizziness
• Somnolence
• Dry mouth
• Peripheral edema
• Weight gain
• Blurred vision
• Difficulty concentrating
• Euphoria
• Withdrawal symptoms upon abrupt discontinuation

Interactions

• CNS depressants may increase the risk of respiratory depression and sedation
• Angiotensin-converting enzyme (ACE) inhibitors may increase the risk of angioedema

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor for signs of misuse, abuse, or dependence
• Consider renal function when prescribing
• Gradual discontinuation is recommended to avoid withdrawal symptoms

Pregnancy

Pregabalin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Animal studies have shown teratogenic effects.

Breast-feeding

Pregabalin is excreted in human milk, and caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place below 25 degrees Celsius. Protect from moisture.

Formulations

• Capsules
• Oral solution

Mechanism of action

Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models. By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. Pregabalin is an anticonvulsant that is structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Pregabalin also has demonstrated analgesic activity. Although pregabalin was developed as a structural analog of GABA, the drug does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors; does not augment GABA-A responses in cultured neurons; and does not alter brain concentrations of GABA in rats or affect GABA uptake or degradation. However, in cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in CNS tissues. ... In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, and substance P, possibly by modulation of calcium channel function. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. ... Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. ... For more Mechanism of Action (Complete) data for PREGABALIN (6 total), please visit the HSDB record page.

Pharmacodynamics

Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.