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Five patients with nocturnal myoclonus (periodic leg movements during sleep), mean age 59.6 years, were monitored polygraphically for fifteen successive nights. Using a double-blind drug study design with placebo at baseline, we investigated the effect of baclofen on these patients. All patients had the repetitive sleep-related abnormal movements during both the baseline nights and those on which baclofen had been administered. The number of movements varied during the four baseline nights, but the movements induced sleep fragmentation, i.e., very short electroencephalographic changes. Baclofen increased the number of movements but decreased their amplitude during non-rapid eye movement (REM) sleep and shortened the interval between movements. Its effect on sleep was dose related: as dosages increased, delta sleep progressively increased and REM sleep decreased. Sleep fragmentation resulting from muscle twitches decreased, as indicated by the diminution in alpha electroencephalographic arousals and K complexes. Baclofen dosages of 20 mg and 40 mg were the most efficacious.

Excessive daytime sleepiness is a complaint characterizing many disorders of the wakefulness--sleep cycle. This paper addresses the complaint of sleepiness objectively by an attempt to differentiate a group of control subjects from a group of patients with unambiguous narcolepsy. Fourteen control and 27 narcoleptic subjects were evaluated by one of three protocols involving nocturnal recordings, detailed interviews, and 5 or more 20-min opportunities to sleep offered at 2-h intervals beginning at 10.00 o'clock, +/- 30 min. Each 20-min opportunity to sleep was given to subjects lying in a darkened quiet room and asked to try to fall asleep. Polysomnographic variables were monitored and sleep was scored in 30-sec epochs by standard criteria. The interval from the start of each test to the first epoch of NREM (including stage 1 sleep) or REM sleep was called sleep latency. In two of the protocols, the subjects were awakened immediately after sleep onset. In the third protocol, the subjects were awakened after 10 min of sleep. Narcoleptics consistently fell asleep much more readily than did control subjects. We conclude that the Multiple Sleep latency test, in addition to providing opportunities to clinically document sleep onset REM sleep periods, can demonstrate pathological sleepiness. Based on these data, we suggest that an average sleep latency less than 5 min be set as the minimum cutoff point for pathological sleepiness.

Six young adult patients with grade I myotonic dystrophy and a complaint of daytime somnolence underwent 36-hour polygraphic monitoring, dynamometric and electromyographic studies before and under baclofen (60 mg/daily). Patients with the most severe daytime sleepiness had pathologic Sleep Apnea Indexes. After 6 weeks' ingestion of baclofen, no subjective or objective effect on patient symptomatology was found.

Eighty-four 4-quinolinehydrazones were synthesized and tested for antiviral activity. Thirty nine derivatives were active against influenza A2 and/or Coxsackie B1 in mice at a dose of 25 mg/kg sc. Structure-activity relationships of 44 derivatives (21 inactive) were analyzed qualitatively using a modified Free-Wilson approach.