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.

To investigate the effect on the sleep EEG, a 1-mg oral dose of SR 46349B, a novel 5-HTThe pivotal role of serotonin (5-hydroxytryptamine, 5-HT) in sleep regulation has been the mainstay of the monoamine theory of sleep (Jouvet 1972). Although the views about the functions of this neurotransmitter have evolved, there is little doubt about its involvement in sleep mechanisms (McCormick 1992). Serotonergic neurons of the nucleus raphe dorsalis are most active during wakefulness and have been proposed to participate in the build-up of sleep propensity (Adrien 1995). Animal studies revealed that these neurons decrease firing upon transition from wakefulness to nonREM sleep (NREMS), and become quiescent during REM sleep (REMS). Thus, deactivation of the serotonergic system may facilitate the production of NREMS and REMS (Adrien 1995). One of the complexities in accounting for the actions of 5-HT is the large number of different receptors and receptor subtypes. 5-HT receptors are classified into four distinct classes, comprising seven fully characterized functional receptor subtypes and several recombinant receptors (Hoyer and Martin 1996). While the involvement of three main classes (i.e., 5-HT 1 , 5-HT 2 , and 5-HT 3 receptors) in the regulation of sleep and wakefulness has been studied, it is the postsynaptic 5-HT 1A receptor that seems to mediate the inhibition of REMS and the promotion of wakefulness, whereas activation of the 5-HT 2 receptor may exert a tonic inhibition of slow wave sleep (SWS) (see Adrien 1995 for review). In relation to sleep homeostasis, the latter is of particular interest because 5-HT 2 antagonists were shown to increase the amount of SWS and to enhance EEG slow-

Informal care is the most important component of costs of care in a mild-to-moderate Alzheimer clinical trial sample, and it is primarily driven by the ADL-ability of the patient. Investigators should focus on the assessment of this economic endpoint because a significant treatment effect on this resource is likely to also affect total costs of care.

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.

A common metric of meaningful difference of FIS was defined across anchors measuring a broad range of HRQOL domains. The MID estimates in the current study can be used for sample size calculation in the planning of future studies and to aid researchers and clinicians in interpreting FIS score differences in patients with MS.