Remacemide is a drug which acts as a low-affinity NMDA antagonist with sodiumchannel blocking properties.[2] It has been studied for the treatment of acute ischemic stroke,[3][4] epilepsy,[5] 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.[6] 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.[citation needed]
Remacemide is also known as remacemide hydrochloride, (±)-2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamide hydrochloride, or FPL 12924AA.[7]
| Other names | (±)-2-amino-N-[1,2-di(phenyl)propan-2-yl]acetamide PR 934-423 |
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Drug interactions[edit]
Levodopa[edit]
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).[18]
Sodium valproate[edit]
Remacemide does not interact with sodium valproate, a treatment for epilepsy.[19]
Carbamazepine[edit]
Ramacemide does interact with carbamazepine. Remacemide inhibits the metabolism of carbamazepine, while carbamazepine induces the metabolism of remacemide and FPL 12495.[20]
Remacemide salts[edit]
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.[21]
Mechanism of action[edit]
Remacemide binds weakly and noncompetitively to the ionic channel site of the NMDA receptor complex.[7] Remacemide binds both allosterically and in the channel.[22] However, because remacemide binds so weakly to NMDAR, much of remacemide's in vivoeffect against excitotoxicity is thought to be caused by its metabolic transformation to the more potent desglycine derivative FPL 12495.[7] That is, remacemide may actually act as a prodrug to deliver the active metabolite FPL 12495 to the central nervous system.[23]
Epilepsy[edit]
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.[24]
FPL 12495[edit]
Much of remacemide's effect in vivo is thought to be caused by the desglycine derivative FPL 12495 (±).[7] FPL 12495 (±) binds specifically and non-competitively to NMDAR.[28] Its effect on maximal electroconvulsive shock is more potent than remacemide.[7]The S isomer (FPL 12859) is even more potent than the racemic mixture, while the R isomer is less potent than the racemate.[7]
FPL 12495 is sometimes referred to as ARL 12495AA.[29][30][31]
Other metabolites[edit]
FPL 15053[edit]
FPL 15053 is the N-hydroxy-desglycinate of remacemide, and exhibits modest binding to NMDAR and modest effects on convulsions and mortality in test mice and rats.[7]
FPL 14331 and FPL 14465[edit]
FPL 14331 and FPL 14465 are the p-hydroxy-desglycinates of remacemide, and they exhibit some efficacy against maximal electroconvulsive shock after i.p. and i.v. dosing.[7]
FPL 15455[edit]
FPL 15455 is an oxoacetate metabolite of remacemide, but has no demonstrated biological activity.[7]
FPL 14991 and FPL 14981[edit]
FPL 14991 and FPL 14981 are both β-Miydroxy-desglycinates of remacemide, and they display modest efficacy against maximal electroconvulsive shock in mice.[7] However FPL 14981 and not FPL 14991 prevents NMDLA-induced convulsions and mortality in mice.[7]
FPL 13592 and FPL 15112[edit]
The hydroxy-methyl derivative of remacemide (FPL 13592) and its desglycinate (FPL 15112) prevents electric shock-induced convulsions only after i.v. administration; only the desglycine derivative binds to NMDAR.[7]
FPL 14467[edit]
FPL 14467 (p-dihydroxy-desglycine) is inactive in vivo and weak in binding NMDAR.[7]
Pharmacodynamics[edit]
The values for 50% displacement of [3H]MK801 were 68 μM for remacemide and 0.48 μM for FPL 12495AA.[7]
Because of remacemide's potential as a neuroprotective agent through preventing glutamate toxicity, it was soon also under investigation as a treatment for Huntington's disease[39] and Parkinson's disease.[40]
https://en.wikipedia.org/wiki/Remacemide
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