Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 1200 mg/day) in a Q.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive N-methyl-D-aspartic acid (NMDA) receptor channel blocker, under investigation in epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of remacemide hydrochloride or placebo, as adjunctive therapy, in 252 adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients were randomized to one of three doses of remacemide hydrochloride (300, 600 or 1200 mg /day) or placebo Q.I.D., for up to 15 weeks. An increasing percentage of responders (defined as a reduction in seizure frequency from baseline of > or =50%) was seen with increasing remacemide hydrochloride dose. At 1200 mg /day, 23% of patients were responders compared with 7% on placebo. This difference was significant (P = 0.016), as was the overall difference between treatments (P = 0.038). Adverse events: dizziness, abnormal gait, gastrointestinal disturbance, somnolence, diplopia and fatigue were mild or moderate in severity. Carbamazepine and phenytoin plasma concentrations were well controlled and maintained within target ranges, with no evidence of improved seizure control due to increases in the concentrations of these drugs. A dose-dependent, significant, increase in responders following adjunctive remacemide hydrochloride compared with placebo was observed. Remacemide hydrochloride was well tolerated.

Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.

PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.

Regenerable fiber-optic-based immunosensor.

An immunosensor is described that is based on fluorescently labeled F(ab') anti-human serum albumin antibody fragments covalently immobilized to the distal end of a fiber-optic probe. When human serum albumin is present, it is bound to the sensor and shields the fluorescent label from the solvent water, and a significant increase in the label fluorescence results. The sensor can be regenerated by simply immersing the sensing tip in chaotropic media. Under these conditions the antigen-antibody complex is selectively disrupted without adversely affecting the sensor. In the present configuration, the same sensor can be recycled over 50 times before the immunosurface inactivates significantly. With proper storage the sensor can last for up to 4 months.

The influence of a social dose of alcohol on the central visual field.

The influence of a socially acceptable dose of alcohol (mean blood alcohol level approximately 90 minutes after ingestion 69.5 mg%; SE 6.20 mg%) on the central visual field as determined by automated static perimetry was investigated in 17 female subjects (17 eyes) trained in automated perimetry (mean age 22.5 years, SE 1.29 years). Central visual field examination was undertaken on the right eye with program 30-2 (stimulus size III) of the Humphrey Field Analyser 630, using a simple cross-over placebo design. Alcohol produced a small (1.0 dB) but statistically significant decrease in the mean deviation (P = 0.002) and small increases (0.6 dB) in the pattern and corrected pattern standard deviations (P = 0.003 and P = 0.046, respectively). The number of stimulus presentations increased by 6% (P = 0.006) and the number of false-negative responses also increased (P = 0.019), indicating impaired patient response. Attenuation of sensitivity as a result of alcohol increased with the increase in eccentricity (P = 0.046) independently of the meridian (P = 0.068) from a mean of 0.8 dB at 3 degrees eccentricity to 1.84 dB at 27 degrees.

Effect of beta-blockers on psychomotor performance in normal volunteers.

The effects of beta-adrenergic receptor antagonists on psychometric tests including vehicle handling, choice reaction time, and kinetic visual acuity (KVA), are reviewed. The beta-blockers had little effect on the performance tests, with the unexplained but reproducible effect of enhanced KVA performance with atenolol. Although the beta-blockers had little effect on performance tests they were shown to have psychotropic effects in normal volunteers. The reasons for the conflicting evidence concerning the effect of these drugs on performance tests is discussed in relation to the present experiments and to variables that may influence response. It is concluded that one should use tests that are as independent as possible from potentially confounding variables. The use of evoked potentials in the electroencephalogram is one such test. A preliminary study is described in which the effects of beta-blockers were detected using visual evoked responses on the electroencephalogram.

Beta-blockers and sleep: a controlled trial.

The effects on sleep of four beta-blockers, atenolol, propranolol, metoprolol and pindolol, were studied in a placebo-controlled trial. Drugs were administered in random order to 10 female volunteers who acted as their own controls. Subjects were tested five times, each test period lasting 10 nights (2 baseline, 2 low dose, 4 high dose, and 2 withdrawal). A questionnaire concerning subjective appreciation of the quality of the previous night's sleep was completed each morning. Night recordings of muscle tension, eye movement, heart rate and electroencephalogram were recorded on paper and magnetic tape. Analysis of the subjective questionnaires showed that recollection of dreaming and awakening in the night was increased by the three lipophilic drugs, propranolol, metoprolol, and pindolol. These results confirm reports in the literature but are contrary to those expected from considering the effects of noradrenaline on sleep. Analysis of physiological records confirmed subjects' reports that waking was increased by the lipophilic drugs. Dreaming (rapid eye movement sleep, REM) was reduced, as predicted from knowledge of the effect of noradrenaline on sleep. Increased awakening leads to an increase in remembered dreaming which explains the otherwise paradoxical results. Although atenolol had no effect on subjective measures of sleep this hydrophilic drug also reduced REM frequency, suggesting that either it has some central effect, or that REM reduction is due to a peripheral 'shielding' effect.

The effects of two antidepressants, imipramine and viloxazine, upon driving performance.

Forty male volunteers were randomly assigned to one of four treatment groups on a double-blind basis: (1) Imipramine--25 mg t.d.s., (2) Viloxazine--50 mg t.d.s., (3) Placebo, and (4) Control--no tablets. Tests were carried out (1) before treatment, (2) 2 h after the first dose, (3) on Day 3 after 7 doses, and (4) on Day 7 after 21 doses. The driving tasks consisted of (1) weaving around a series of bollards while simultaneously responding to an auditory logic task and (2) a gap acceptance task. Using an analysis of covariance repeated measures design, it was found that imipramine tended to increase the level of risk acceptable to the subject as compared to either placebo or control. Imipramine also impaired performance on other tasks. Viloxazine appeared to be little different from either placebo or control on any of the tasks.

The effects of four antihypertensive agents on the Stroop colour-word test in normal male volunteer subjects.

Sixty healthy male volunteers were randomly assigned to one of six treatment groups on a double-blind basis: 1. Atenolol = 50 mg t.d.s. 2. Methyl dopa = 250 mg t.d.s. 3. Propanolol = 40 mg t.d.s. 4. Reserpine = 0.2 mg t.d.s. 5. Placebo. 6. Control = no tablets. Tests were carried out before treatment, 2 h after the first dose, after seven doses, and after 21 doses. Subjects performance on the Stroop Colour-Word Test was assessed in terms of (a) word reading speed and (b) an 'interference' score based on the difference between the incongruous colour word and colour card reading speed. No evidience was found of central effects of the beta-blockers, but personality X drug interactions were found, particularly in the reserpine group.