indication

For management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia.

pharmacology

Pregabalin is a new anticonvulsant drug indicated as an add on therapy for partial onset seizures and for certain types of neuropathic pain. It was designed as a more potent successor to a related drug, gabapentin. Pregabalin binds to the alpha2-delta subunit of the voltage-gated calcium channel in the central nervous system. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on 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 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.

mechanism of action

Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalinís antinociceptive and antiseizure effects in animal models. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.

biotransformation

Negligible

absorption

Well absorbed after oral administration.

half life

~6 hours

route of elimination

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.