"Lubeluzole"

of symptom onset. [15] No further trials are planned.LubeluzoleThe exact mechanism of action of lubeluzole, a drug effective in animal models, is unclear. The drug may block sodium channels in cells. In addition, it may reduce the release of nitric oxide, a neurotransmitter generated by activation of the NMDA receptor. Although stroke severity and patient age appeared to influence outcome in early studies , [17] a later trial was unable to confirm that lubeluzole was effective in these subsets of acute stroke patients [18] . Clinical stroke research with this drug has been abandoned.ClomethiazoleClomethiazole, a gamma-aminobutyric acid agonist, decreases excitatory neurotransmission by increasing activity of inhibitory pathways. [19] In Europe, clomethiazole's central nervous system inhibitory

of symptom onset. [15] No further trials are planned.LubeluzoleThe exact mechanism of action of lubeluzole, a drug effective in animal models, is unclear. The drug may block sodium channels in cells. In addition, it may reduce the release of nitric oxide, a neurotransmitter generated by activation of the NMDA receptor. Although stroke severity and patient age appeared to influence outcome in early studies , [17] a later trial was unable to confirm that lubeluzole was effective in these subsets of acute stroke patients [18] . Clinical stroke research with this drug has been abandoned.ClomethiazoleClomethiazole, a gamma-aminobutyric acid agonist, decreases excitatory neurotransmission by increasing activity of inhibitory pathways. [19] In Europe, clomethiazole's central nervous system inhibitory

of symptom onset. [15] No further trials are planned.LubeluzoleThe exact mechanism of action of lubeluzole, a drug effective in animal models, is unclear. The drug may block sodium channels in cells. In addition, it may reduce the release of nitric oxide, a neurotransmitter generated by activation of the NMDA receptor. Although stroke severity and patient age appeared to influence outcome in early studies , [17] a later trial was unable to confirm that lubeluzole was effective in these subsets of acute stroke patients [18] . Clinical stroke research with this drug has been abandoned.ClomethiazoleClomethiazole, a gamma-aminobutyric acid agonist, decreases excitatory neurotransmission by increasing activity of inhibitory pathways. [19] In Europe, clomethiazole's central nervous system inhibitory

of symptom onset. [15] No further trials are planned.LubeluzoleThe exact mechanism of action of lubeluzole, a drug effective in animal models, is unclear. The drug may block sodium channels in cells. In addition, it may reduce the release of nitric oxide, a neurotransmitter generated by activation of the NMDA receptor. Although stroke severity and patient age appeared to influence outcome in early studies , [17] a later trial was unable to confirm that lubeluzole was effective in these subsets of acute stroke patients [18] . Clinical stroke research with this drug has been abandoned.ClomethiazoleClomethiazole, a gamma-aminobutyric acid agonist, decreases excitatory neurotransmission by increasing activity of inhibitory pathways. [19] In Europe, clomethiazole's central nervous system inhibitory

Lubeluzole in acute ischemic stroke. A double-blind, placebo-controlled phase II trial. Lubeluzole International Study Group. We aimed to assess the safety and efficacy of lubeluzole in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in the carotid artery territory. A randomized, double-blind, placebo-controlled multicenter trial was conducted in 232 patients. Because placebo, 66 lubeluzole 7.5 mg over 1 hour followed by 10 mg/d for 5 days, and 66 lubeluzole 15 mg over 1 hour followed by 20 mg/d for 5 days. The trial, initially aimed at a patient inclusion of 270, was terminated prematurely according to the advice of the Safety Committee because of an imbalance in mortality between the treatment groups. Mortality rates at the final follow-up of 28 days for placebo

outcome was investigated in 1375 ischaemic stroke patients who had been included in two placebo-controlled trials with lubeluzole. The endpoint was a favourable outcome, defined as a modified Rankin Scale score < or =2 at 3 months. Classification into lacunar (n = 168) and non-lacunar (n = 1207) strokes was based on clinical criteria according to the Oxfordshire Community Stroke Project and findings

Lubeluzole in acute ischemic stroke treatment: A double-blind study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebo. This trial was a double-blind, placebo-controlled, phase III trial with an 8-hour inclusion window to assess the efficacy and safety of an intravenous loading dose of 7.5 mg followed by a daily intravenous dose of 10 mg lubeluzole for 5 days in acute ischemic stroke patients. A total of 1786 patients were randomized: 901 to lubeluzole and 885 to placebo. Overall, 212 patients (23.5%) from the lubeluzole group and 213 (24.1%) from the placebo group discontinued the trial prematurely. In the lubeluzole group 201 patients (22.3%) discontinued because of adverse events compared with 193 patients (21.8%) in the placebo group. The primary

. Data from the placebo arm of the Lubeluzole-International-9 trial were reviewed to identify patients with fatal brain edema. Early clinical, laboratory, and radiographic parameters were evaluated in a case-control design. Initial CT scans were analyzed for early ischemic abnormalities by 2 blinded investigators. Twenty-three patients died from brain swelling, with minimum baseline National Institutes

Combination Therapy Stroke Trial: recombinant tissue-type plasminogen activator with/without lubeluzole. A neuroprotective drug may be safe and effective if given very early and in combination with recombinant tissue-type plasminogen activator (rt-PA) to acute stroke patients. No clinical trial has yet tested this hypothesis. To assess the feasibility, safety and efficacy of simultaneously combining the neuroprotective drug lubeluzole with rt-PA. Patients who qualified for and received rt-PA within 3 h of symptom onset were randomly allocated 1:1 to lubeluzole (7.5 mg i.v. over 1 h, then continuous 5-day infusion of 10 mg/day) or placebo. Infusion of the study medication was started before the end of the 1-hour rt-PA infusion. Inclusion criteria were the same as those of the FDA-approved

Combination therapy stroke trial. rt-PA +/- lubeluzole.

The safety and tolerability of single intravenous doses of lubeluzole (Prosynap) in healthy volunteers. The safety and tolerability of single escalating doses of lubeluzole were evaluated in healthy male volunteers in 2 studies. In the first of 2 randomized, single-blind, placebo-controlled, dose-escalation studies, 6 subjects received single 30-minute infusions of 2.5, 5, and 10 mg of lubeluzole , and 2 additional subjects received placebo. In the second study 6 different subjects received a 1-hour infusion of 15 mg of lubeluzole, 5 of whom received the 20-mg dose, and 2 received 25 mg of lubeluzole. Two additional subjects received placebo. Small increases and decreases in PQ, QRS, QT, QTc, and QTm intervals were noted after infusion of all lubeluzole doses and placebo, however, these changes

Cardiovascular safety of lubeluzole (Prosynap(R)) in patients with ischemic stroke. The cardiovascular safety of lubeluzole was evaluated in patients with ischemic stroke in a double-blind, placebo-controlled trial. Forty-six patients were randomized to receive a continuous daily infusion of lubeluzole 5 mg (loading dose 3.75 mg over 1 h), lubeluzole 10 mg (loading dose 7.5 mg over 1 h ), or placebo for 5 days within 24 h of stroke onset. The primary measure of cardiovascular safety was the QTc interval, derived from the continuous electrocardiogram (ECG) and measured during treatment and a 2-day follow-up. Compared with placebo. Neither dosage of lubeluzole had any statistically or clinically relevant effects on the QTc. Neither were there any significant differences among the three

Determination of the dose proportionality of single intravenous doses (5, 10, and 15 mg) of lubeluzole in healthy volunteers. The dose proportionality of lubeluzole, a drug in clinical development for the treatment of acute ischemic stroke, was evaluated in a Phase I, single-center, open-label, randomized-dosing-sequence, three-way crossover clinical trial in 12 healthy adults. An equal number of male and female volunteers were enrolled in the trial, with a mean weight (+/- SD) of 73.2 +/- 11.9 kg, mean height (+/- SD) of 66.8 +/- 4.6 inches, and a mean age of 36.1 +/- 5.2 years. Subjects received intravenous infusions of 5 (A), 10 (B), and 15 mg (C) of lubeluzole over 1 hour on three separate occasions, with a minimum washout period of 2 weeks. The treatment sequences were A-B-C; A-C-B; B

Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group. Lubeluzole is a novel benzothiazole compound that has shown neuroprotective activity in preclinical models of ischemic stroke. The present multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of lubeluzole in the treatment of ischemic stroke . Seven hundred twenty-one patients with clinical symptoms of acute ischemic stroke were randomized to receive either lubeluzole (7.5 mg over 1 hour, followed by a continuous daily infusion of 10 mg for up to 5 days) or placebo. Treatment was initiated within 6 hours of symptom onset. Mortality at 12 weeks was the primary efficacy end point. Secondary efficacy end points included neurological recovery

Pharmacokinetics of lubeluzole (Prosynap) after single intravenous doses in healthy subjects. The single-dose pharmacokinetics of lubeluzole were investigated in 2 single-blind, placebo-controlled, dose-escalation studies in healthy male subjects. In the first study, 6 subjects received an intravenous infusion of 2.5, 5, and 10 mg lubeluzole. In the second study, a 15 mg dose of lubeluzole was administered to 6 subjects, of whom 5 also received 20 mg and 2 also 25 mg lubeluzole. Following the infusion, plasma lubeluzole concentrations decayed biphasically, with a mean distribution half-life (t1/2alpha) of 30 to 65 minutes and a mean terminal half-life (t1/2beta) of 15 to 24 hours. The results of the 2 studies indicate that lubeluzole exhibits linear kinetics over the dose range tested in healthy

Multinational randomised controlled trial of lubeluzole in acute ischaemic stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group. Lubeluzole is a benzothiazole derivative that has shown neuroprotective properties in different experimental models. This multicentre, double-blind, placebo-controlled trial was conducted to assess the safety and efficacy of lubeluzole in patients with an acute ischaemic stroke. Patients who presented with clinical signs and symptoms of acute cerebral hemispheric ischaemic stroke were randomised to intravenous therapy with placebo (n = 360) or lubeluzole 7.5 mg over 1 h followed by 10 mg/day for up to 5 days (n = 365). Treatment was initiated within 6 h of symptom onset. Mortality at 12 weeks was the primary end point. Secondary end points included

Safety and pharmacokinetics of the neuroprotective drug lubeluzole in patients with ischemic stroke. A total of 22 patients with acute ischemic stroke participated in two randomized, single-masked, placebo-controlled studies that evaluated the safety and pharmacokinetics of single escalating intravenous doses of lubeluzole. The first dose of study medication in all patients was given within 6 hours of the first sign of stroke onset. In the first study, 6 patients received a single 1-hour intravenous infusion of 5 mg of lubeluzole; 4 of these patients received an additional 10-mg dose 3 to 4 days later. Two additional patients received placebo. In the second study, 4 patients received a single 1-hour infusion of 10 mg of lubeluzole, and 2 patients received placebo. After a safety evaluation

stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months

Effects of the neuroprotectant lubeluzole on the cytotoxic actions of veratridine, barium, ouabain and 6-hydroxydopamine in chromaffin cells 1. Incubation of bovine adrenal chromaffin cells with veratridine (10-100 microM) during 24 h, caused a concentration-dependent release of the cytosolic lactate dehydrogenase (LDH) into the bathing medium, an indicator of cell death. Lubeluzole or its R (-) enantiomer, R91154, did not enhance LDH release. Both lubeluzole and R91154 (0.3-10 microM) decreased the veratridine-induced LDH release. 2. Penfluridol did not increase LDH release at concentrations 0.003-1 microM; 3-10 microM increased LDH release to 50-60%, after 24 h exposure. Penfluridol (0.03-0.3 microM) did not protect against the cytotoxic effects of veratridine; at 1 microM, 15% protection

Differential effects of the neuroprotectant lubeluzole on bovine and mouse chromaffin cell calcium channel subtypes 1. The effects of lubeluzole (a neuroprotective benzothiazole derivative) and its (-) enantiomer R91154 on whole-cell currents through Ca2+ channels, with 10 mM Ba2+ as charge carrier (IBa), have been studied in bovine and mouse voltage-clamped adrenal chromaffin cells. Currents generated by applying 50 ms depolarizing test pulses to 0 mV, from a holding potential of -80 mV, at 10 s intervals had an average magnitude of 1 nA. 2. Lubeluzole and R91154 blocked the peak IBa of bovine chromaffin cells in a time and concentration-dependent manner; their IC50s were 1.94 microM for lubeluzole and 2.54 microM for R91154. In a current-voltage protocol, lubeluzole (3 microM) inhibited peak