Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease.

The neuropeptides neurokinin B, neurotensin, and anandamide, the endogenous ligands of NK3, NT1, and CB1 receptors respectively, are known to interact with brain dopaminergic transmission. This study evaluated the effects of these three antagonists of the NK3 (SR 142801), neurotensin (SR 48692), and cannabinoid (SR 141716) receptors on the severity of motor symptoms and levodopa-induced dyskinesias after administration of a single dose of levodopa in 24 patients with Parkinson disease. In this exploratory randomized, double-blind, placebo-controlled study, at the dose used, the drugs tested were well tolerated and could not improve parkinsonian motor disability.

Serotonin-2 receptors and human sleep: effect of a selective antagonist on EEG power spectra.

To investigate the effect on the sleep EEG, a 1-mg oral dose of SR 46349B, a novel 5-HT2 antagonist, was administered three hours before bedtime. The drug enhanced slow wave sleep (SWS) and reduced stage 2 without affecting subjective sleep quality. In nonREM sleep (NREMS) EEG slow-wave activity (SWA; power within 0.75-4.5 Hz) was increased and spindle frequency activity (SFA; power within 12.25-15 Hz) was decreased. The relative NREMS power spectrum showed a bimodal pattern with the main peak at 1.5 Hz and a secondary peak at 6 Hz. A regional analysis based on bipolar derivations along the antero-posterior axis revealed significant 'treatment' x 'derivation' interactions within the 9-16 Hz range. In enhancing SWA and attenuating SFA, the 5-HT2 receptor antagonist mimicked the effect of sleep deprivation, whereas the pattern of the NREMS spectrum differed.

Clinical and electrophysiological study of the peripheral nervous system in the elderly.

The effect of age on the peripheral nervous system was investigated by clinical examination and neurophysiological studies in 59 subjects aged 60-103 years and 23 young subjects. A full laboratory screen for factors which, though clinically silent, may constitute risk factors (RFs) for peripheral neuropathy was also performed in the elderly subjects. Our findings show that the presence of RFs affects exceptionally the electrophysiological parameters in a statistically significant way. The age-dependent changes in nerve conduction parameters were well predicted by non-linear models. The simultaneous electromyographical study demonstrates the re-innervation capacity of the motor system.

Metabolic and circulatory evaluation of cerebral ischemic accident in humans by positron emission tomography: a pilot study with almitrine-raubasine.

Positron emission tomography and oxygen-15 were used to evaluate the effect of almitrine-raubasine combination on cerebral blood flow and oxidative metabolism in patients with cerebral ischemia. In five patients aged between 58 and 74 years, with a cerebral ischemic accident in the territory of the middle cerebral artery, blood flow rate, oxygen metabolic rate, and cerebral oxygen extraction were measured before and after a 90-min intravenous perfusion of almitrine bismesilate 15 mg and raubasine 5 mg. Investigations were performed from day 2 to day 7 after stroke occurred. One patient showed evidence of initial relative luxury perfusion, the degree of which was reduced by such combined treatment. The other four patients had a focal reduction in cerebral blood flow and oxygen consumption prior to treatment. The statistical analysis of three cerebral areas (epicenter of lesion, anterior and posterior juxtalesional areas, and homologous heterolateral areas) showed a 3.6% increase in oxygen metabolic rate at the epicenter, when both hemispheres were taken together, and a significant increase in cerebral blood flow in all three areas (3% on the healthy hemisphere, 13% on the injured hemisphere). These changes were greater in some patients than in others. This suggests that heterogeneity of drug responses may correspond to the heterogeneity of the initial status.

Efficacy of almitrine-raubasine in cognitive disorders of aging: a double-blind, placebo-controlled, clinical and psychometric study.

Early treatment of age-related cognitive impairment can be decisive in enabling elderly patients to remain at home. A double-blind, placebo-controlled trial of almitrine-raubasine was conducted in 40 elderly outpatients (25 women, 15 men; mean age: 73.5 years) with moderate cognitive impairment randomized into two groups, one receiving almitrine and raubasine, the other placebo, two tablets daily for 90 days. They were assessed at T0, T45 and T90 days, using the Toulouse-Pieron test, 8 subtests from the Wechsler Adult Intelligence Scale (WAIS) and the Sandoz Clinical Assessment for Geriatrics (SCAG). End-of-study results were significantly better in the almitrine-raubasine group in all tests: Toulouse-Pieron test (p less than 0.001), WAIS (p less than 0.001), and SCAG (p less than 0.001).