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CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affinity for other receptors. Although originally developed by Novo Nordisk A/S as NNC-687 for the treatment of schizophrenia, the company changed its therapeutic focus in the mid-1990s and the full rights to CEE-03-310 and several related compounds were subsequently granted to CeNeS Pharmaceuticals in 1999. CeNeS is currently investigating the drug's potential in the treatment of insomnia and alcohol dependency [340965], [382293], [401496],[416026]. A phase II, double-blind, placebo-controlled trial of CEE-03-310 demonstrated a dose-dependent enhancement of NREM sleep at the beginning of the night without any effects on the quantity of REM sleep [410739].

Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of difficulty awakening in the morning. Dawn simulation has been found effective in treating SAD, but its effect on difficulty awakening has not been assessed. Fifty medication-free patients with SAD associated with hypersomnia were randomized to receive either 1 week of dawn simulation (250 lux) or a dim (0.2-2 lux) placebo signal. The patients assessed their level of drowsiness upon awakening during the baseline week and during the treatment week using the Stanford sleepiness scale (SSS). A psychiatrist rated difficulty awakening after the baseline week and after the treatment week. Dawn simulation lowered both the difficulty awakening score (P<0.05) and the SSS score (P<0.05) compared to the placebo dawn signal. Replication is necessary. No biological markers of circadian phase were measured. Compared to a placebo condition, dawn simulation appears effective in decreasing both prospectively assessed morning drowsiness and retrospectively assessed difficulty awakening. The symptom of difficulty awakening is consistent with the phase delay hypothesis of SAD. Assessment of difficulty awakening could prove useful in the evaluation of SAD.

Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young healthy men by the use of identical paired stimuli. In this study, the exploration of the gating paradigm was extended with the addition of a mixed modality paradigm where three different pairs of identical stimuli (clicks, right median nerve electric stimulations and proprioceptive stimuli of changing load on a handheld weight) were presented over a 12-s cycle. In both modalities repeated measures analyses of variance demonstrated no effect of paradigm. This mixed-modality recording paradigm could be used in further experiments to examine gating deficits across modalities.

A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schizophrenia, we might expect the processing deficits to act on multiple modalities. We have examined the gating of median nerve somatosensory EP (SEP) following paired stimulation identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of 500, 750 and 1000 ms and the correlation of gating to the skin conductance orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and 0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45 in N80 in the AEP. Repetition effects in the two modalities were not correlated. AEP P50 gating was correlated to skin conductance level (SCL). The combination of recording repetition effects on the mid-latency EP in two modalities could provide a method for investigating if deficits of information processing in schizophrenia are cross-modal.