Biomedical subjects
Publications and source records attributed to K Inanaga.
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The theta activity which appears in the frontal midline area during performance of mental tasks has been designated as "Fm theta". In the present study, the possible use of zopiclone as an anxiolytic agent was investigated using Fm theta, in a comparison with diazepam. Sixteen male university students were given placebo, diazepam 5 mg, zopiclone 5 mg and 10 mg, in a double-blind, cross-over design. EEGs were recorded before and during performance of an arithmetic addition test. This test was repeated twice, prior to and 1 h following drug administration. Diazepam markedly increased Fm theta; however, both zopiclone 10 mg and placebo only slightly affected Fm theta, while zopiclone 5 mg failed to affect Fm theta. Scores of state anxiety were reduced markedly by diazepam and only slightly by zopiclone 10 mg, but were not affected by either zopiclone 5 mg or by placebo. Task performance was reduced markedly and in a dose-dependent manner by zopiclone, and very slightly by diazepam. These results suggest that zopiclone possesses a rather potent hypnotic effect, rather than an anxiolytic effect, and that Fm theta might be a useful tool in predicting the clinical efficacy of anxiolytic drugs in normal humans.
The averaged photopalpebral reflex (PPR) represents the mean of summed reflex contractions of the orbicularis oculi muscle in response to periodic photic stimuli. The latency of PPR can be used to assess a drug effect on human arousal level, since it is prolonged if there is a reduction in the arousal level of the subject. In the present study of the clinical effects of zopiclone, healthy male volunteers aged 18-22 years were given zopiclone 5 mg and 10 mg, nitrazepam 5 mg and 10 mg, or placebo, in a double-blind, cross-over design. Changes in the latencies of PPR were examined from 0.5 to 4 h after medication. Both zopiclone and nitrazepam prolonged the latency in a dose-dependent manner, but the prolongation induced by zopiclone appeared more rapidly, was slightly more marked and lasted for a shorter period than that induced by nitrazepam. Zopiclone produced slightly fewer subjective changes, such as vagueness of thought and weakness, than did nitrazepam. From these results, it is suggested that zopiclone possesses a potent hypnotic action which appears more rapidly and is slightly more potent and shorter lasting than that of nitrazepam. In addition, zopiclone may also exhibit fewer side effects, such as vagueness of thought and weakness than nitrazepam, and it may cause less "hang over".
In 1981, Inanaga et al reported on the efficacy of DN-1417 (a TRH analog) in the treatment of degenerative myoclonus epilepsy and other forms of intractable epilepsy. Following this report, we studied the efficacy and safety of DN-1417 treatment in 10 intractable epileptic children ranging in age from 6 months to 11 years (mean 4 years), including 7 with Lennox syndrome (LS), 2 with West syndrome (WS) and 1 with degenerative myoclonus epilepsy (DME). The daily dose was from 0.02 to 0.05 mg/kg, initially, and then was increased to 0.05 mg/kg. Complete control of seizures was achieved in 2 patients with LS, a 50% or greater decrease in seizure frequency was observed in one patient each with LS and DME and a less than 50% decrease in 1 with LS and 2 with WS. There was no change in 2 LS cases, and 1 LS case became worse. Activation of psychic activities, such as psychomotor activity, facial expression and motivation, was also noted in 7 of the 10 patients. Furthermore, improvement of motor function was noted in 5 patients. Electroencephalographic abnormalities improved in 2 completely seizure free patients with LS in which EEG ameliorated along with clinical seizure control.
The photopalpebral reflex (PPR) is a useful method to assess level of arousal. Healthy males were given either brotizolam (0.0625, 0.125, 0.25 or 0.5 mg) or placebo within a double-blind, crossover design. Changes in PPR and subjective assessments were observed for 5 h after medication. Prolongation of the latencies of PPR were dose dependent, and the amplitude tended to be reduced. These effects appeared within 30 min, and lasted about 4 h. The dose-response curve of the maximum prolongation of the latencies was linear. Sleepiness and slight ataxia were observed after drug ingestion. Sleepiness was correlated with the prolongation of the PPR latencies. Brotizolam could be a potent hypnotic, with rapid onset and moderate duration of action, and it has no severe side-effects.
The averaged photopalpebral reflex (PPR) was bipolarly recorded from electrodes placed on the upper and lower palpebrae in male university students. In a drowsy state which was defined by the monitored EEG, the latencies of PPR were significantly prolonged and the amplitude reduced. In contrast, the latencies were shortened by immersing their hands in ice water which greatly aroused the subjects. The central stimulant, methylphenidate 10 mg, significantly shortened the latencies and diazepam 5 mg possessing anxiolytic and hypnotic actions significantly prolonged them. When the recording of PPR was repeated consecutively five times, the amplitude was easily reduced but the latencies were relatively stable. From these results, it is confirmed that the latencies of PPR are prolonged in a lowered arousal level and shortened in a more aroused state. This indicates that PPR could be a useful index to assess objectively the arousal level of humans and hence could be a useful tool for investigations of psychophysiology and psychopharmacology.
The clinical effects of zopiclone were predicted by using two psychophysiological tests: the averaged photopalpebral reflex and the frontal midline theta activity. Zopiclone at 5 and 10 mg showed a rapid, dose-dependent, moderately lasting prolongation of the latencies of the averaged photopalpebral reflex related to the lowering of the arousal level. Diazepam 5 mg increased markedly the frontal midline theta activity, the appearance of which seems to be related to the relief from anxiety, while zopiclone 10 mg only slightly modified the frontal midline theta activity. The results suggest that zopiclone possesses a potent hypnotic effect, whereas its anxiolytic potential in humans is probably low.
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We carried out a quantitative fluorescent histochemical analysis in rats in order to clarify the effects of chronic treatment with haloperidol on the central dopamine turnover. Long-term treatment with haloperidol showed no significant reduction of dopamine fluorescence intensities in the n. caudatus putamen, the n. accumbens, and the tuberculum olfactorium. This suggests that tolerance is established after long-term treatment with haloperidol in both mesolimbic and nigrostriatal dopamine systems, whereas tolerance is not observed in the tuberoinfundibular dopamine system.
The present experiment was designed to demonstrate the presence of a constant rhythm or periodicity in the appearance of Fm theta using the Mirror Drawing Test (MDT), a task with a changing degree of difficulty. Thirty male university students were recorded on the EEGs during performance of the MDT for 5 min. Fm theta appeared most frequently in the block requiring the longest time for passage, or the most difficult block. The present study further revealed that Fm theta tended to appear mainly from four points at about 40, 90, 190 and 270 sec after beginning the MDT. From these results, the appearance of Fm theta was shown to be more distinctly related to the concentration of attention. In the process of concentration and attention distraction, the presence of a rhythm with a periodicity of approximately 45 sec was suggested.
The efficacy of timiperone in schizophrenia as compared with perphenazine was assessed in a double-blind fashion in 205 patients throughout a 12-week treatment period. More than half of the subjects were chronic schizophrenics. Global improvement in the timiperone treatment group was superior to that in the perphenazine group in view of a lower rate of aggravation. With regard to overall safety and general usefulness rating, there were no significant differences between the two drug treatments. However, timiperone showed less frequency of excitability, irritability, anxiety and anorexia than perphenazine on occasions during the 12 week treatment period. From these results it may be concluded that the efficacy of timiperone could be superior or equivalent to that of perphenazine which has been confirmed to be of use as an antipsychotic.
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