PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Lacosamide”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

18 recordsLinked to original sources
PubMed2007

Lacosamide.

Lacosamide is a new chemical entity being investigated as an adjunctive treatment for epilepsy, as well as monotherapy for diabetic neuropathic pain. Lacosamide appears to have a dual mode of action: selective enhancement of sodium channel inactivation and modulation of collapsin response mediator protein-2. Rapidly and completely absorbed after oral administration, lacosamide has an elimination half-life of approximately 13 hours and a low potential for drug interactions. Additionally, lacosamide exhibits linear, dose-proportional pharmacokinetics with low intra- and interpatient variability. Randomized controlled trials of adjunctive lacosamide (200, 400, and 600 mg/day) have demonstrated statistically significant reduction in median seizure frequency compared with placebo. In addition, 50% responder rates for lacosamide (400 and 600 mg/day) were statistically superior to placebo. The most frequently reported adverse events (> or =10% of lacosamide-treated patients) included dizziness, headache, and nausea. A double-blind, double-dummy randomized trial of intravenous lacosamide (30- and 60-minute infusion) as replacement for oral lacosamide showed that the safety and tolerability profiles were comparable for intravenous and oral lacosamide. The efficacy and safety results from completed clinical trials, as well as the favorable pharmacokinetic profile, suggest that lacosamide may represent a significant advance in antiepileptic drug therapy.

Acetamides↗
PubMed2005

Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain.

Lacosamide is a functionalized amino acid which was initially synthesized as an antiepileptic drug. In addition to its broad anti-seizure activity, lacosamide was shown to display efficacy in animal models for neuropathic pain and is currently in phase III clinical development for the treatment of epilepsy and neuropathic pain. In order to further profile its antinociceptive properties, the effects of lacosamide on inflammatory pain in the formalin test, the carrageenan model and the adjuvant-induced arthritis model were investigated. For the formalin test, mice received an intraplantar injection of formalin and the subsequent licking response was measured over 45 min. Lacosamide was administered 30 min before formalin. For the carrageenan model, mechanical and thermal hyperalgesia were assessed 3 h following an intraplantar injection of carrageenan. Lacosamide was administered to rats 30 min before pain threshold measurements. For the adjuvant-induced arthritis test rats received intraplantar injections of Freund's complete adjuvant into the right hindpaw which lead to the development of arthritic symptoms in all animals tested for antinociception. On day 11 after arthritis induction, mechanical hyperalgesia was assessed by the modified Randall Selitto paw pressure test following acute treatment with lacosamide. Lacosamide dose-dependently attenuated mechanical hyperalgesia following carrageenan injection and in rats suffering from Freund's complete adjuvant-induced arthritis. Moreover, thermal hyperalgesia induced by carrageenan as well as the formalin-induced licking response were dose-dependently attenuated by lacosamide. These results suggest lacosamide may be active against various forms of acute and chronic inflammatory pain in humans.

Acetamides↗
PubMed2006

Effects of the novel antiepileptic drug lacosamide on the development of amygdala kindling in rats.

PURPOSE: The current treatment of epilepsy focuses exclusively on the prophylaxis or suppression of seizures and thus provides merely a symptomatic treatment, without clear influence on the course of the disease. There is a need for new drugs that act at different molecular targets than currently available antiepileptic drugs (AEDs) and for new therapies designed to block the process of epileptogenesis. In recent years, different research lines have examined the epileptogenic process in order to understand the different stages in this process, and with the hope that early recognition and intervention could prevent the development or progression of epilepsy. In animals, acquired epilepsy is studied most commonly with the kindling model and status epilepticus models. In the present study, we used the kindling model to evaluate whether the novel AED lacosamide affects kindling-induced epileptogenesis. This drug does not seem to act by any of the mechanisms of currently available AEDs, but the exact molecular mechanisms of action of lacosamide have not yet been clarified. METHODS: Groups of 9-10 rats were treated with either vehicle or different doses of lacosamide (3, 10, or 30 mg/kg/day) over 22-23 days during amygdala kindling. RESULTS: Daily administration of lacosamide during kindling acquisition produced a dose-dependent effect on kindling development. While the drug was inactive at 3 mg/kg/day, significant retardation of kindling was observed at 10 mg/kg/day, by which the average number of stimulations to reach kindling criterion was increased by >90%. A significant inhibitory effect on kindling acquisition was also observed with 30 mg/kg/day, but this dose of lacosamide was associated with adverse effects. CONCLUSIONS: The present data demonstrate that lacosamide, in addition to exerting anticonvulsant activity, has the potential to retard kindling-induced epileptogenesis. Whether this indicates that lacosamide possesses antiepileptogenic or disease-modifying potential needs to be further evaluated, including studies in other models of acquired epilepsy.

Acetamides↗
PubMed2006

Lacosamide, a new anti-epileptic, alleviates neuropathic pain-like behaviors in rat models of spinal cord or trigeminal nerve injury.

The effect of systemic administration of lacosamide, a newly developed anti-epileptic, on neuropathic pain-like behaviors was examined in rats after ischemic injury to the infraorbital nerve or spinal cord using a photochemical method. In rats with infraorbital nerve injury, lacosamide reduced mechanical hypersensitivity and the effect was markedly stronger in female than in male rats. In spinal cord injured female rats 10-20 mg/kg lacosamide dose-dependently alleviated the mechanical and cold allodynia-like behaviors without causing motor impairments or marked sedation. Administration of lacosamide twice daily at 20 mg/kg for 7 days totally alleviated the allodynia-like state in spinally-injured rats with no tolerance. Following treatment cessation the cold and the static allodynia reappeared but the effect on dynamic mechanical allodynia (brushing) was maintained until day 11. Lacosamide also produced hypothermia at antinociceptive doses in rats. It is suggested that this novel compound may be useful as an analgesic for treating central and trigeminal neuropathic pain. Furthermore, there may be a gender difference to the effect of lacosamide with female rats being more responsive to the treatments.

Acetamides↗
PubMed2005

Stereoselective effects of the novel anticonvulsant lacosamide against 4-AP induced epileptiform activity in rat visual cortex in vitro.

We examined effects of the novel anticonvulsant lacosamide and its inactive isomer (SPM 6953) in an in vitro model of epileptiform activity. Focal field potential recordings (34+/-0.2 degrees C) were obtained from 17 to 22 day old rat brain slices. Physiological synaptic transmission (fEPSP amplitude and duration) in CA1 of rat hippocampus was not significantly altered (P > 0.05, n = 4) by lacosamide (1 microM-1 mM). Recording from visual cortex during application of 4-aminopyridine (4-AP; 100 microM) revealed both spontaneous and evoked 'ictal like' discharges. Spontaneous ictal like discharges in the visual cortex were blocked by 100 microM carbamazepine (CBZ), 100 microM pentobarbital and 200 microM phenobarbital (PHB) but were insensitive to the anti-absence drug ethosuximide (750 microM; n = 4, P > 0.05). Lacosamide reduced tonic duration and maximal firing frequency with EC(50)s of 41 and 71 microM, respectively. In contrast, the S stereoisomer (100-320 microM) produced no significant effect on spontaneous ictal activity (n = 3-4, P > 0.05). Seizures induced by high frequency (100 Hz, 1s) stimulation were selectively reduced in amplitude by PHB (200 microM) and frequency by CBZ (100 microM; n = 6) and lacosamide (100 microM; n = 4). GABAergic negative going potentials were attenuated by CBZ (irreversible with washing) and lacosamide (reversible) but not by PHB. We conclude that lacosamide blocks 4-AP induced epileptiform activity in the visual cortex. This novel anticonvulsant drug appears to inhibit epileptogenesis (seizure spread) by interacting with a stereoselective, but as yet unidentified, target site in rodent neocortex in the mid-micromolar range.

2-Amino-5-phosphonovalerate↗
PubMed2006

Antinociceptive efficacy of lacosamide in a rat model for painful diabetic neuropathy.

Lacosamide was tested in the streptozotocin rat model of diabetic neuropathic pain in comparison to drugs which are commonly used in the treatment of diabetic neuropathic pain, i.e. antidepressants and anticonvulsants. In diabetic rats, lacosamide attenuated cold (10, 30 mg/kg, i.p.), warm (3, 10, 30 mg/kg, i.p.) and mechanical allodynia (30 mg/kg, i.p.). Streptozotocin-induced thermal and mechanical hyperalgesia were reduced by lacosamide at doses of 10 and 30 mg/kg, i.p. Morphine (3 mg/kg) showed similar efficacy on allodynia and hyperalgesia. Amitriptyline (10 mg/kg), venlafaxine (15 mg/kg), levetiracetam (180 mg/kg) and pregabalin (100 mg/kg) exhibited significant effects on thermal allodynia and mechanical hyperalgesia. Only treatment with amitriptyline (30 mg/kg, i.p.) produced full reversal of thermal allodynia comparable to lacosamide. Lamotrigine (45 mg/kg, i.p.) had no effect on both behavioral readouts. Lacosamide's potency and efficacy in reversing pain behavior might be due to its new, yet unknown mechanism of action.

Acetamides↗
PubMed2005

The novel antiepileptic drug lacosamide blocks behavioral and brain metabolic manifestations of seizure activity in the 6 Hz psychomotor seizure model.

Brain metabolic activation after 6 Hz electrical stimulation (32 mA, 3s stimulus duration) was assessed by autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake. In addition, effects of the new antiepileptic drug lacosamide were examined on the stimulation-induced metabolic activation. The 6 Hz stimulation via corneal electrodes induced a robust increase 2-DG uptake in cerebral cortical regions, lateral amygdala, and the caudate-putamen. Many other brain regions were not affected by the stimulation, including the hippocampal formation, medial nuclei of the amygdala, thalamus, and hypothalamus. Lacosamide (20 mg/kg) injected i.p. 30 min before application of electrical stimulation antagonized completely the seizure-induced brain metabolic activation but did not affect basal 2-DG uptake. The data provide evidence that lacosamide antagonizes the neural activation induced by an electrical seizure stimulus, without suppressing normal brain metabolic activity.

Acetamides↗
PubMed2006

Seeking a mechanism of action for the novel anticonvulsant lacosamide.

Lacosamide (LCM) is anticonvulsant in animal models and is in phase 3 assessment for epilepsy and neuropathic pain. Here we seek to identify cellular actions for the new drug and effects on recognised target sites for anticonvulsant drugs. Radioligand binding and electrophysiology were used to study the effects of LCM at well-established mammalian targets for clinical anticonvulsants. 10 microM LCM did not bind with high affinity to a plethora of rodent, guinea pig or human receptor sites including: AMPA; Kainate; NMDA (glycine/PCP/MK801); GABA(A) (muscimol/benzodiazepine); GABA(B); adenosine A1,2,3; alpha1, alpha2; beta1, beta2; M1,2,3,4,5; H1,2,3; CB1,2; D1,2,3,4,5; 5HT1A,1B,2A,2C,3,5A,6,7 and KATP. Weak displacement (25%) was evident at batrachotoxin site 2 on voltage gated Na+ channels. LCM did not inhibit neurotransmitter transport mechanisms for norepinephrine, dopamine, 5-HT or GABA, nor did it inhibit GABA transaminase. LCM at 100 microM produced a significant reduction in the incidence of excitatory postsynaptic currents (EPSC's) and inhibitory postsynaptic currents (IPSC's) in cultured cortical cells and blocked spontaneous action potentials (EC50 61 microM). LCM did not alter resting membrane potential or passive membrane properties following application of voltage ramps between -70 to +20 mV. The voltage-gated sodium channel (VGSC) blocker phenytoin potently blocked sustained repetitive firing (SRF) but, in contrast, 100 microM LCM failed to block SRF. No effect was observed on voltage-clamped Ca2+ channels (T-, L-, N- or P-type). Delayed-rectifier or A-type potassium currents were not modulated by LCM (100 microM). LCM did not mimic the effects of diazepam as an allosteric modulator of GABA(A) receptor currents, nor did it significantly modulate evoked excitatory neurotransmission mediated by NMDA or AMPA receptors (n > or = 5). Evidently LCM perturbs excitability in primary cortical cultures but does not appear to do so via a high-affinity interaction with an acknowledged recognition site on a target for existing antiepileptic drugs.

Acetamides↗
PubMed2006

Diverse mechanisms of antiepileptic drugs in the development pipeline.

There is a remarkable array of new chemical entities in the current antiepileptic drug (AED) development pipeline. In some cases, the compounds were synthesized in an attempt improve upon the activity of marketed AEDs. In other cases, the discovery of antiepileptic potential was largely serendipitous. Entry into the pipeline begins with the demonstration of activity in one or more animal screening models. Results from testing in a panel of such models provide a basis to differentiate agents and may offer clues as to the mechanism. Target activity may then be defined through cell-based studies, often years after the initial identification of activity. Some pipeline compounds are believed to act through conventional targets, whereas others are structurally novel and may act by novel mechanisms. Follow-on agents include the levetiracetam analogs brivaracetam and seletracetam that act as SV2A-ligands; the valproate-like agents valrocemide, valnoctamide, propylisopropyl acetamide, and isovaleramide; the felbamate analog flurofelbamate, a dicarbamate, and the unrelated carbamate RWJ-333369; the oxcarbazepine analog licarbazepine, which probably acts as a use-dependent sodium channel blockers, and its prodrug acetate BIA 2-093; various selective partial benzodiazepine receptor agonists, including ELB139, which is a positive allosteric modulator of alpha3-containing GABA(A) receptors. A variety of AEDs that may act through novel targets are also in clinical development: lacosamide, a functionalized amino acid; talampanel, a 2,3-benzodiazepine selective noncompetitive AMPA receptor antagonist; NS1209, a competitive AMPA receptor antagonist; ganaxolone, a neuroactive steroid that acts as a positive modulator of GABA(A) receptors; retigabine, a KCNQ potassium channel opener with activity as a GABA(A) receptor positive modulator; the benzanilide KCNQ potassium channel opener ICA-27243 that is more selective than retigabine; and rufinamide, a triazole of unknown mechanism.

Animals↗
PubMed2006

Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII).

The Eigth Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT VII, took place in Sitges, Barcelona from the 10th to 14th September, 2006. Basic scientists, clinical pharmacologists and neurologists from 24 countries attended the conference, whose main themes included a focus on status epilepticus (epidemiology, current and future treatments), evidence-based treatment guidelines and the potential of neurostimulation in refractory epilepsy. Consistent with previous formats of this conference, the central part of the conference was devoted to a review of AEDs in development, as well as updates on marketed AEDs introduced since 1989. This article summarizes the information presented on drugs in development, including brivaracetam, eslicarbazepine acetate (BIA-2-093), fluorofelbamate, ganaxolone, huperzine, lacosamide, retigabine, rufinamide, seletracetam, stiripentol, talampanel, valrocemide, JZP-4, NS1209, PID and RWJ-333369. Updates on felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and new extended release oxcarbazepine formulations, pregabalin, tiagabine, topiramate, vigabatrin, zonisamide and new extended release valproic acid formulations, and the antiepileptic vagal stimulator device are also presented.

Anticonvulsants↗
PubMed2006

New antiepileptic drugs that are second generation to existing antiepileptic drugs.

In the last decade, 10 new antiepileptic drugs (AEDs) have been introduced that offer appreciable advantages in terms of their favourable pharmacokinetics, improved tolerability and lower potential for drug interactions. However, despite the large therapeutic range of old and new AEDs, approximately 30% of the patients with epilepsy are still not seizure free and, consequently, there is a substantial need to develop new AEDs. The new AEDs currently in development can be divided into two categories: drugs with completely new chemical structures such as lacosamide (formally harkoseride), retigabine, rufinamide and talampanel; and drugs that are derivatives or analogues of existing AEDs that can be regarded as second-generation or follow-up compounds of established AEDs. This article focuses on the second category and thus critically reviews the following second-generation compounds: eslicarbazepine acetate or BIA-2-093 and 10-hydroxy carbazepine (carbamazepine derivatives); valrocemide and NPS 1776 (isovaleramide; valproic acid derivatives); pregabalin and XP13512 (gabapentin derivatives); brivaracetam (ucb 34714) and seletracetam (ucb 44212; levetiracetam derivatives); and fluorofelbamate (a felbamate derivative). In addition, a series of valproic acid derivatives that are currently in preclinical stage has also been evaluated because some lead compounds of this series have a promising potential to become new antiepileptics and CNS drugs. For any of these follow-up compounds to become a successful second generation to an existing AED, it has to be more potent, safer and possess favourable pharmacokinetics, including low potential for pharmacokinetic and pharmacodynamic drug interactions.

Amines↗
PubMed2004

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride.

Double-Blind Method↗
PubMedDate not supplied

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T 4; NBI-56418, NCX-4016, nesiritide, nicotine conjugate vaccine, NSC-330507; Oglufanide, omalizumab, oxipurinol; Palifermin, palonosetron hydrochloride, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, PEGylated interferon alfacon-1, perospirone hydrochloride, pimecrolimus, pixantrone maleate, plerixafor hydrochloride, PowderJect lidocaine, pradefovir mesylate, prasterone, pregabalin, Prostvac VF, PT-141, PTC-124, pyridoxamine; QS-21, quercetin; R-126638, R-411, ralfinamide, rasagiline mesilate, rF-PSA, RG-2077, rhThrombin, rimonabant hydrochloride, rofecoxib, rosuvastatin calcium, rotigotine hydrochloride, rV-PSA; S-18886, S-303, seocalcitol, SGN-40, sitaxsentan sodium, SPP-301, St. John's Wort extract; Tadalafil, taxus, telithromycin, tenatoprazole, tenofovir disoproxil fumarate, testosterone MDTS, testosterone transdermal patch, tgAAC-09, TH-9507, thioacetazone, tipifarnib, TQ-1011, trabectedin, travoprost, trimethoprim; Valdecoxib, valganciclovir hydrochloride, valopicitabine, voriconazole; Xcellerated T cells.

Clinical Trials as Topic↗
PubMed2006

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus-eluting stent, sitaxsentan sodium, solifenacin succinate, Staphylococcus aureus vaccine; Tadalafil, talactoferrin alfa, talaporfin sodium, Taxus, tecadenoson, tegaserod maleate, telithromycin, temsirolimus, tenofovir disoproxil fumarate, teriparatide, terutroban sodium, tesaglitazar, tesmilifene hydrochloride, TG-100115, tigecycline, torcetrapib; Ularitide; Valproic acid, sodium, voriconazole; Zotarolimus, zotarolimus-eluting stent.

Clinical Trials as Topic↗
PubMedDate not supplied

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749, sirolimus-eluting stent, solifenacin succinate, sunitinib malate; Tadalafil, talampanel, tasidotin hydrochloride, Taxus, tegaserod maleate, telavancin hydrochloride, tenofovir disoproxil fumarate, tiotropium bromide, tocilizumab, tositumomab, treprostinil sodium, tridolgosir hydrochloride, TTS-CD3; Ularitide; Valdecoxib, Val-Tyr sardine peptidase, vardenafil hydrochloride hydrate, voriconazole; Yttrium (90Y) edotreotide, Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zucapsaicin.

Clinical Trials as Topic↗
PubMed2006

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent.

Clinical Trials as Topic↗
PubMed1999

The anticonvulsant activities of N-benzyl 3-methoxypropionamides.

We recently reported that the ED50 value for (R,S)-2,3-dimethoxypropionamide (1) in the maximal electroshock (MES)-induced seizure test in mice was 30 mg/kg (Choi, D.; Stables, J.P., Kohn, H. Bioorg. Med. Chem. 1996, 4, 2105). This value is comparable to that observed for phenobarbital (ED50 = 22 mg/kg). Compound 1 is structurally similar to a class of MES-selective anticonvulsant agents, termed functionalized amino acids (2), that were developed in our laboratory. The distinguishing feature of 2 is the differential activities observed for enantiomers. In this study, we asked whether comparable differences in activities were observed in the MES-induced seizure test for (R)- and (S)-1. We developed stereospecific syntheses for these enantiomers and showed that both compounds exhibit nearly equal anticonvulsant activity in mice (i.p.) (MES ED50 = 79-111 mg/kg). The surprisingly high ED50 values for (R)- and (S)-1 required our redetermining the ED50 value for (R,S)-1. We revised this value to 79 mg/kg. A limited structure-activity relationship study for 1 was conducted. Special attention was given to the C(2) methoxy unit in 1. We found that replacement of this moiety led to only modest differences in the MES activities upon ip administration to mice. Significantly, we observed an enhancement in the anticonvulsant activity for (R,S)-N-benzyl 2-hydroxy-3-methoxypropionamide ((R,S)-6) upon oral administration to rats ((R,S)-6: mice (i.p.) ED50 > 100, < 300 mg/kg; rat (oral) ED50 = 62 mg/kg). The activities of 3-methoxypropionamides, functionalized amino acids, and related compounds are discussed.

Acetamides↗