Pregabur Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Pregabalin binds to an auxiliary subunit (α2-δ protein) of voltage-gated calcium channels in the central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, 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 pregabalin's antinociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium dependent release of pronociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing calcium channel trafficking and/or reducing currents. Evidence from other animal models of nerve damage and persistent pain suggest the antinociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gammaaminobutyric acid (GABA), it does not bind directly to GABA_A, GABA_B, 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.
Pharmacokinetics: Oral bioavailability of Pregabalin is estimated to be ≥90% and is independent of dose. In humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 L/kg. Pregabalin is not bound to plasma proteins. Following a dose ratio labeled pregabalin approximately 98% of the administered dose recovered in the urine was unchanged pregabalin. Its mean elimination half-life is 6.3 hours