Pharmacodynamics<unk>  is a functionalized amino acid that produces activity in the maximal electroshock seizure (MES) test, that, like some other antiepileptic drugs (AEDs), are believed to act through voltage-gated sodium channels.<unk>  enhances the slow inactivation of voltage-gated sodium channels without affecting the fast inactivation of voltage-gated sodium channels. This inactivation prevents the channel from opening, helping end the action potential. Many antiepileptic drugs, like carbamazepine or lamotrigine, slow the recovery from inactivation and hence reduce the ability of neurons to fire action potentials. Inactivation only occurs in neurons firing action potentials; this means that drugs that modulate fast inactivation selectively reduce the firing in active cells. Slow inactivation is similar but does not produce complete blockade of voltage gated sodium channels, with both activation and inactivation occurring over hundreds of milliseconds or more.<unk>  makes this inactivation happen at less depolarized membrane potentials. This means that<unk>  only affects neurons which are depolarized or active for long periods of time, typical of neurons at the focus of epilepsy.<unk>  administration results in the inhibition of repetitive neuronal firing, the stabilization of hyperexcitable neuronal membranes, and the reduction of long-term channel availability, but does not affect physiological function.<unk>  has a dual mechanism of action. It also modulates collapsin response mediator protein 2 (CRMP-2), preventing the formation of abnormal neuronal connections in the brain.<unk>  does not affect AMPA, kainate, NMDA, GABAA, GABAB or a variety of dopaminergic, serotonergic, adrenergic, muscarinic or cannabinoid receptors and does not block potassium or calcium currents.<unk>  does not modulate the reuptake of neurotransmitters including norepinephrine, dopamine, and serotonin. In addition, it does not inhibit GABA transaminase. Preclinical research In preclinical trials, the effect of<unk>  administration on animal models of epilepsy was tested using the Frings audiogenic seizures (AGS)-susceptible mouse model of seizure activity with an effective dose (ED50) of 0.63 mg/kg, i.p. The effect of<unk>  was also assessed using the MES test to detect inhibition of seizure spread.<unk>  administration was successful in preventing the spread of seizures induced by MES in mice (ED50 = 4.5 mg/kg, i.p.) and rats (ED50 = 3.9 mg/kg, p.o.). In preclinical trials, administration of<unk>  in combination with other AEDs resulted in synergistic anticonvulsant effects.<unk>  produced effects in animal models of essential tremor, tardive dyskinesia, schizophrenia, and anxiety. Preclinical trials found the S-stereoisomer to be less potent than the R-stereoisomer in the treatment of seizures. Pharmacokinetics When administered orally in healthy individuals,<unk>  is rapidly absorbed from the gastrointestinal tract. Little of the drug is lost via the first pass effect, and thus has an oral bioavailability of nearly 100%. In adults,<unk>  demonstrates a low plasma protein binding of d value just under 5μM and a Bmax of about 200 pM/mg. The volume of distribution (Vd) of<unk>  in plasma is 0.6 L/kg, which is close to the total volume of water.<unk>  is ampiphilic and is thus hydrophilic while also lipophilic enough to cross the blood-brain barrier.
Lacosamide
Galantamine
Tianeptine
Benzonatate
Gliquidone
Mannitol
Zonisamide
Acotiamide