Disease relevance of FPL 12924

• Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson's disease [1].
• CONCLUSIONS: On the evidence of this study, the maximum well-tolerated dose for remacemide hydrochloride in acute stroke is 400 mg BID [2].
• Effects of remacemide and its metabolite FPL 12495 on spike-wave discharges, electroencephalogram and behaviour in rats with absence epilepsy [3].
• Lamotrigine and remacemide protect striatal neurons against in vitro ischemia: an electrophysiological study [4].
• The purpose of this study was to assess the role of an excitatory amino acid (EAA) receptor antagonist (remacemide hydrochloride) in a rabbit model of subarachnoid hemorrhage (SAH)-induced cerebral vasospasm [5].

Psychiatry related information on FPL 12924

• When monoamine-depleted rats were treated with a subthreshold dose of levodopa methylester, remacemide hydrochloride (5-40 mg/kg, orally) caused a dose-dependent increase in locomotor activity [1].
• Several compounds were not effective in either improving motor skills or prolonging life, including Remacemide (a glutamate antagonist), Celecoxib (a COX-2 inhibitor), and Chlorpromazine (a prion inhibitor); Celecoxib dramatically shortened life expectancy [6].
• Remacemide exhibits efficacy against maximal electroconvulsive shock (MES) in rodents and seizures elicited by N-methyl-D,L-aspartate (NMDLA) in mice [7].
• Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model [8].
• Remacemide caused profound and long-lasting, perhaps permanent, changes in learning task performance and because performance of this same task by children is significantly correlated with traditional measures of intelligence (IQ), these data suggest that such treatment may provide a valuable model of chemically-induced mental retardation [9].

High impact information on FPL 12924

• The hypothesis that remacemide, an NMDA receptor antagonist, would provide protection against such ischemic damage has been tested in a randomized trial [10].
• Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during coronary artery bypass in 171 patients [10].
• The neuroprotective actions of remacemide and its anticonvulsant metabolite 1,2-diphenyl-2-propylamine monohydrochloride (desglycinylremacemide; DGR) a low-affinity NMDA receptor antagonist, were investigated using primary rat cortical neuronal cultures [11].
• This review comparatively evaluates the pharmacokinetics of the following 10 new antiepileptic drugs: felbamate, flunarizine, gabapentin, lamotrigine, oxcarbazepine, remacemide, stiripentol, tiagabine, topiramate and vigabatrin [12].
• A combined use of lamotrigine and remacemide could be employed in clinical trials to enhance neuroprotection in neurological disorders involving an abnormal striatal glutamatergic transmission [4].

Chemical compound and disease context of FPL 12924

• These findings suggest that in this model EAAs may cooperate in the genesis of SAH-induced cerebral vasospasm and that NMDA receptor antagonism with remacemide hydrochloride can partially prevent the SAH-induced vasospasm of a large cerebral artery [5].
• Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease [13].

Biological context of FPL 12924

• Actions of the anticonvulsant remacemide metabolite AR-R12495AA on afferent-evoked spinal synaptic transmission in vitro and on models of acute and chronic inflammation in the rat [14].
• This SRF limitation was concentration-dependent, and equipotent IC50 values of 66 and 60 microM were calculated for remacemide hydrochloride and ARL 12495AA, respectively [15].
• However, in CBZ-treated patients, the AUC of remacemide and its active metabolite was 60 and 30%, respectively, of values observed in healthy volunteers treated previously with the same dose [16].
• Lamotrigine, remacemide, and the active desglycinyl metabolite of remacemide, D-REMA, induced a concentration-dependent reduction of both repetitive firing discharge and excitatory postsynaptic potentials [4].
• The plasma method was also applied to measurement of in vitro plasma protein binding of remacemide in rat, dog and human plasma [17].

Anatomical context of FPL 12924

• METHODS: One hundred seventy-one patients undergoing coronary artery bypass surgery by a single cardiothoracic surgical team were randomized to receive remacemide (up to 150 mg every 6 hours) or placebo from 4 days before to 5 days after their bypass procedure [10].
• The blocking actions of the remacemide enantiomers and their des-glycinates were investigated in whole cell voltage-clamp recordings from cultured rat hippocampal neurons and in binding studies with [3H]dizocilpine in rat forebrain membranes [18].
• The effects of the anticonvulsant remacemide [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamide hydrochloride] and its metabolite AR-R12495AA [(+/-)-1-methyl-1, 2-diphenylethylamine-monohydrochloride] on primary afferent synaptic transmission were assessed in the young rat spinal cord in vitro [14].
• Na(+) channel effects of remacemide and desglycinyl-remacemide in rat cortical synaptosomes [19].
• Data indicate that remacemide enters the brain by passive diffusion and undergoes deglycination at the blood-brain barrier or within the brain to give FPL12495 [20].

Associations of FPL 12924 with other chemical compounds

• METHODS: A randomized, double-blind, placebo-controlled cross-over study of add-on remacemide hydrochloride was performed in 10 of 14 recruited patients being treated with CBZ monotherapy [16].
• The anticonvulsant action of remacemide (RCM) is probably largely due to blockade of NMDA receptors and prolonged inactivation of sodium channels induced by its desglycinated metabolite [21].
• Unlike that with remacemide hydrochloride and ARL 15896AR, oral administration of the high-affinity uncompetitive NMDA receptor-antagonists phencyclidine, ARL 16247 [N-(3-ethylphenyl)-N-methyl-N'-naphthylguanidine] and MK-801 engendered phencyclidine-like stereotypy at doses near their MES ED50 values [22].
• Drugs in development include those at an advanced stage, such as topiramate and tiagabine, as well as those just entering clinical trials, such as remacemide and levetiracetam [23].
• METHODS: In a group of 12 healthy adult male volunteers, the single dose and steady-state kinetics of remacemide were each determined twice, once in the absence and once in the presence of phenobarbitone [24].

Gene context of FPL 12924

• We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD [13].
• Similar effects on isoform-selective P450-dependent activities were observed in male and female mice treated with remacemide as part of a dose-ranging study.(ABSTRACT TRUNCATED AT 250 WORDS)[25]
• 7. These findings may have relevance to the clinical use of remacemide hydrochloride in human epilepsy [26].
• FPL 13950 continues to serve as a potential backup candidate for remacemide HCl which is currently in clinical trials for patients with stroke and epilepsy [27].
• CoQ10 is presently being studied as a potential treatment for early PD as well as in combination with remacemide as a potential treatment for HD [28].

Analytical, diagnostic and therapeutic context of FPL 12924

• Doses of 200 mg BID or higher attained the putative neuroprotective plasma concentrations of remacemide predicted from animal models (250 to 600 ng/mL) [2].
• Oxcarbazepine and remacemide have high hepatic clearance and are biotransformed to hydroxy and deglycine metabolites, respectively, with the activity of their metabolites contributing to the antiepileptic activity of the parent drug after oral administration, despite high first-pass effect metabolism [12].
• There were no important effects on behaviour and on spectral content of the background EEG, suggesting that remacemide has little side effects [3].
• The electrophysiological actions of the putative anticonvulsants remacemide hydrochloride and its des-glycine metabolite ARL 12495AA were examined using whole-cell recordings from CA1 hippocampal neurons in adult rat brain in vitro [15].
• A high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of both remacemide (a novel anticonvulsant and cerebroprotectant) and an active, major metabolite in human plasma [29].

References