Neurosantin Mechanism of Action

Pharmacology: Gabapentin is structurally related to the neurotrans­mitter GABA (gamma-aminobutyric acid) but its mech­anism of action is different from that of several other drugs that interact with GABA synapses including valproate, barbiturates, benzodiazepines, GABA trans­aminase inhibitors GABA uptake inhibitors, GABA agonists, and GABA prodrugs. In vitro studies with radio­ labeled Gabapentin have characterized a novel peptide binding site in rat brain tissues including neo­cortex and hippocampus that may relate to anti­ convulsant activity of Gabapentin and its structural derivates.
Gabapentin at relevant clinical concentrations does not bind to other common drug or neurotransmitter receptors of the brain including GABA_A, GABA_B, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate receptors.
Gabapentin does not interact with sodium channels in vitro and so differs from phenytoin and carbamazepine. Gabapentin partially reduces responses to the glutamate agonist N-methyl-D-aspartate (NMDA) in some test systems in vitro, but only at concentrations greater than 100 µM, which are not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro.
Pharmacokinetic: Gabapentin bioavailability is not dose-proportional. That is, as the dose is increased, bioavailability decreases. Following oral administration, peak plasma Gabapentin concentration are observed within 2 to 3 hours. Absolute bioavailability of Gabapentin capsules is approximately 60%. Food, including a high-fat diet, has no effect on Gabapentin pharmacokinetics.
Gabapentin elimination from plasma is best described by linear pharmacokinetics.
The elimination half-life of Gabapen tin is independent of dose and averages 5 to 7 hours.
Gabapentin pharmacokinetics are not effected by repeated administration, and steady state plasma concentrations are predictable from single dose data. Plasma Gabapentin concentrations are dose proportional at doses of 300 or 400 mg given every 8 hours.
Pharmacokinetic parameters are given in Table 1 as follows.


Click on icon to see table/diagram/image


Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 liters. In patients with epilepsy, Gabapentin concentrations in Cerebro spinal fluid (CSF) are approximately 20% of corre­sponding steady-state trough plasma concentrations. Gabapentin is eliminated solely by renal excretion. There is no evidence of metabolism in man. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
In elderly patients, and in patients with impaired renal function, Gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.
Gabapentin is removed from plasma by hemodialysis. Dosage adjustment in patients with compromised renal function or undergoing hemodialysis is recommended.
In general, plasma Gabapentin concentrations in children are similar to those in adults.