Remacemide Remacemide is a drug which acts as a low-affinity NMDA antagonist with sodium channel blocking properties. It has been studied for the treatment of acute ischemic stroke, epilepsy, Huntington's disease, and Parkinson's disease. Because remacemide has only a modest effect on seizure frequency and causes dizziness, it is no longer believed that remacemide will be an effective treatment for epilepsy. Although no such statement has been made about remacemide's potential for treating stroke, Huntington's, or Parkinson's, remacemide is no longer being developed for these conditions. Remacemide is also known as remacemide hydrochloride, (±)-2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamide hydrochloride, or FPL 12924AA. Adverse effects dizziness nausea Lack of adverse effects Unlike many other treatments for epilepsy, remacemide does not appear to impair cognitive performance or driving performance in humans, although the evidence for effects on cognitive performance in animals has been mixed. Remacemide is not a sedative. Toxicity The median toxic dose of remacemide for neural impairment tests in mice is 5.6 mg/kg. Its estimated median lethal dose is about 927.3 mg/kg in mice. It has a favorable therapeutic index of 28.1 in mice. Drug interactions Levodopa Remacemide delays the absorption of levodopa (300 mg of remacemide one hour before levodopa treatment delays mean time to peak levodopa plasma concentration by 20%) but not its total absorption (area-under-the-curve for levodopa plasma concentration was unchanged). Sodium valproate Remacemide does not interact with sodium valproate, a treatment for epilepsy. Carbamazepine Ramacemide does interact with carbamazepine. Remacemide inhibits the metabolism of carbamazepine, while carbamazepine induces the metabolism of remacemide and FPL 12495. Alcohol Remacemide salts Remacemide is most commonly synthesized as the salt remacemide hydrochloride. However, there has been some investigation into other remacemide salts and their crystals, as different remacemide salts might taste more pleasant or have a solubility more suitable for a pediatric suspension formulation. Mechanism of action Remacemide binds weakly and noncompetitively to the ionic channel site of the NMDA receptor complex. Remacemide binds both allosterically and in the channel. However, because remacemide binds so weakly to NMDAR, much of remacemide's in vivo effect against excitotoxicity is thought to be caused by its metabolic transformation to the more potent desglycine derivative FPL 12495. That is, remacemide may actually act as a prodrug to deliver the active metabolite FPL 12495 to the central nervous system. Epilepsy In a well validated and described genetic model of absence epilepsy, rats of the WAG/Rij strain, remacemide and its metabolite FPL 12495 were found to have a common for glutamate antagonist usual effect on the number of spike/wave dischargesEEG, the drugs decrease spike/wave dischanges dose dependently. However, in contrast to most other glutamate antagonists, FPL 12495 increased the duration of the spike-wave discharges. Pharmacokinetics Blood–brain barrier The brain uptake index (BUI), a measure of a drug's ability to pass the blood–brain barrier that involves the injection of radiolabeled test and reference substances into the common carotid artery of anesthetized animals, for remacemide is 51 ± 0.9 SD. Enantiomers The (-)stereoisomer of remacemide is of equal potency to the racemic mixture in preventing maximal electroshock seizures when administered orally to rats, while the (+)stereoisomer is less potent. Metabolites FPL 12495 Much of remacemide's effect in vivo is thought to be caused by the desglycine derivative FPL 12495 (±). FPL 12495 (±) binds specifically and non-competitively to NMDAR,. Its effect on maximal electroconvulsive shock is more potent than remacemide. The S isomer (FPL 12859) is even more potent than the racemic mixture, while the R isomer is less potent than the racemate. FPL 12495 is sometimes referred to as ARL 12495AA. Other metabolites FPL 15053 FPL 15053 is the N-hydroxy-desglycinate of