The effect of zolpidem and zopiclone on memory.

The effect of 10 mg of zolpidem (ZLP) on memory function was evaluated in healthy male adults using word recall test, passage recall test, and Sternberg's memory scanning task. This study was carried out as a double-blind cross-over study with 7.5 mg of zopiclone (ZPC) and a placebo. No difference was noted between the active drugs and placebo in the number of words recalled from the word list presented before administration. No evidence of retrograde amnesia was suggested. However, encoding ability was slightly affected as indicated by a decrease in the number of words recalled from the list presented after administration. Slight impairment of a delayed recall was noted for both of the active drugs, but the effect disappeared the next morning. In the memory scanning task, ZLP prolonged a non-specific component of reaction time 1.5 h after administration, but the effect disappeared after 12.5 h. ZPC did not prolong the reaction time. The two active drugs showed no specific effects on either memory scanning or response-selection stage in short-term memory at any time. The findings suggest that residual effects did not reach clinical significance at the standard dosage, although the active drugs slightly affected encoding ability and retention soon after administration.

The effects of zolpidem and zopiclone on daytime sleepiness and psychomotor performance.

Zolpidem (ZLP), which has selective affinity to the BZ1 (omega 1) receptor and a short half-life, is a novel hypnotic. The objective of this study is to compare the residual effects of standard clinical doses of ZLP and zopiclone (ZPC), a short-acting hypnotic marginally selective for the BZ1 (omega 1) receptor, given in a single dose on daytime sleepiness and psychomotor function. This study was carried out as a double-blind cross-over study with 10 mg ZLP, 7.5 mg ZPC and a placebo in 12 healthy male adults. In the multiple sleep latency test, sleep latency was not reduced but increased by ZLP and ZPC as well as the placebo when drug plasma levels had nearly reached the peak. Subjects administered ZLP were significantly more feeble, lethargic and antagonistic in mood rating scales than those administered ZPC. The incidence of severe behavioral side effects was higher in the case of ZLP than in the case of ZPC over the same period. Sleep latency the next morning was significantly shorter in the case of ZPC than in the case of ZLP or the placebo. The tapping test performed at the same time demonstrated that the number of taps was significantly less in the case of ZPC than in the case of ZLP or the placebo. The results of the present study suggest that ZLP acts more rapidly than ZPC. On the other hand, ZLP has less residual effect on sleepiness and psychomotor function the next morning.

Pharmacokinetic and pharmacodynamic interactions among haloperidol, carteolol hydrochloride and biperiden hydrochloride.

A beta-adrenoceptor blocker and an anticholinergic agent are often prescribed concomitantly for the treatment of neuroleptic-induced akathisia. The aim of this study was to investigate possible pharmacokinetic interactions of neuroleptic haloperidol with the beta-blocker carteolol and the anticholinergic biperiden. In a 5-step, open-labeled, oral single-dose study, eight healthy male volunteers received 2 mg haloperidol, 10 mg carteolol hydrochloride, and 2 mg biperiden hydrochloride: first each drug alone, then a combination of haloperidol and carteolol, and then all three drugs concurrently. Serum concentrations of haloperidol, carteolol, and biperiden were determined up to 24 hr postdosing, and a safety evaluation was conducted throughout the study. Carteolol increased the area under the haloperidol serum concentration-time curve (AUC0-t) 1.4-fold (P = 0.0014) and decreased the serum clearance of haloperidol up to 67% (P = 0.0127). Biperiden reduced the serum haloperidol concentrations increased by the administration of carteolol. No significant changes of the serum pharmacokinetics of carteolol and biperiden were found as a result of any drug combinations. Adverse events of the central nervous system such as sleepiness and changes in pupil size were observed, but all were mild with clinical insignificance.

A comparative study of the psychological effects of DN-2327, a partial benzodiazepine agonist, and alprazolam.

The effects of single oral doses of DN-2327 (DN, 2 mg or 3 mg), a newly developed partial benzodiazepine receptor agonist, and alprazolam (APZ, 0.8 mg), a full receptor agonist, on psychomotor function and short-term memory were assessed using three psychometric tests: letter cancellation, visual vigilance and Sternberg's memory scanning task. Twelve healthy male volunteers participated in this study. Randomized, double-blind, cross-over test sessions were conducted at 2-week intervals. Both 3 mg DN and 0.8 mg APZ increased the time to completion of the letter cancellation task at 3 h after administration, but neither had any effect on accuracy of response. In the visual vigilance task, which required relatively intense concentration and continuous attention, both the number of errors and reaction times to correct responses significantly increased from 1.5 to 3.5 h after administration of 3 mg DN and at 3.5 h after administration with 0.8 mg APZ. DN at 2 mg also significantly increased the number of errors from 1.5 to 3.5 h after administration, but it did not affect reaction times. In the memory scanning task, 3 mg DN, but not 2 mg DN or APZ, significantly increased overall reaction times at 2 h after administration. These performance deficits paralleled the time-course changes in serum concentrations of both drugs and appeared to be associated with the hypnotic-sedative effects of the drugs tested. These findings did not support those of previous preclinical studies of DN, indicating superiority of DN over conventional full benzodiazepine agonists/anxiolytics in terms of adverse behavioral consequences.

Effects of tandospirone, a 5-HT1A receptor-related anxiolytic, on daytime sleepiness and psychomotor functions: a comparative double-blind study with diazepam.

A double-blind cross-over placebo-controlled study was designed to compare the effects of a single oral dose of tandospirone (30 mg), a new 5-HT1A receptor-related anxiolytic, on daytime sleepiness, psychomotor function and short-term memory with those of diazepam (5 mg), a benzodiazepine, in 12 healthy Japanese volunteers. A dose of 5 mg of diazepam significantly shortened sleep latencies measured by the Multiple Sleep Latency Test during the periods of 3 to 7 h after the medication, with no influence on the self-estimated sleepiness on the Stanford Sleepiness Scale. The elevated daytime sleepiness under the diazepam treatment was correlated with impaired psychomotor performance; performance on the visual vigilance task significantly declined 1.5 to 3.5 h after the administration of 5 mg of diazepam. In contrast, 30 mg of trandospirone did not impair objective measures of daytime wakefulness or performances. The differential effects of the two anxiolytics on daytime sleepiness and psychomotor functions could be ascribable to the differences in their pharmacological mechanisms of actions. The findings also suggested the superiority of tandospirone to the benzodiazepine in terms of behavioral side effects.