PRETIMOL

Indications

• Acute pain
• Chronic pain
• Postoperative pain
• Neuropathic pain

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines for pediatric populations.

Adults: Refer to the BNF for specific dosing information based on the clinical scenario.

Mechanism of action

Flupirtine upregulates Bcl-2, increases glutathione levels, activates inwardly rectifying potassium channels, and delays loss of intermitochondrial membrane calcium retention capacity. It acts as an NMDA receptor antagonist without binding to the receptor. Its discriminative effects are mediated primarily through alpha-2 adrenergic mechanisms.

Pharmacodynamics

Flupirtine's analgesic effects are attributed to its ability to modulate pain transmission pathways and enhance endogenous analgesic mechanisms. By increasing glutathione levels and modulating calcium retention in mitochondria, it contributes to neuroprotection and reduces neuronal excitability, which may help alleviate pain.

Pharmacokinetics

Flupirtine is well-absorbed following oral administration, with peak plasma concentrations typically achieved within 1 to 2 hours. It is extensively metabolized in the liver, primarily via conjugation with glucuronic acid and oxidation. The elimination half-life ranges from 6 to 12 hours, and it is excreted mainly via the urine as metabolites.

Pregnancy

There is insufficient data on the use of flupirtine in pregnant women. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Flupirtine is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Mechanism of action

Flupirtine upregulates Bcl-2, increases glutathione levels, activates an inwardly rectifying potassium channel, and delays loss of intermitochondrial membrane calcium retention capacity. Flupirtine acts like a NMDA receptor antagonists, but does not bind to the receptor. One study concluded that the discriminative effects of flupirtine are neither of opioid nor of alpha-1 adrenergic type, but are primarily mediated through alpha-2 adrenergic mechanisms [PMID: 2901483].