The impact of age on the hypnotic effects of eszopiclone and zolpidem in the guinea pig

Abstract

Rational Eszopiclone and zolpidem are hypnotics that differentially affect sleep and waking states in adult animals. Therefore, it was of interest to compare their effects on the states of sleep and wakefulness in aged animals. Objectives Our objective was to determine the responses to eszopiclone and zolpidem vis-à-vis sleep and waking states in aged guinea pigs and to compare them with the effects of these hypnotics in adult animals. Methods Aged guinea pigs were prepared to monitor sleep and waking states and to perform a frequency analysis of the EEG. Eszopiclone and zolpidem were administered intraperitoneally (1, 3, and 10 mg/kg). Results Eszopiclone produced a more rapid and greater increase in NREM sleep as well as longer duration episodes of NREM sleep compared with zolpidem. There was also a significant increase in the latency to REM sleep with eszopiclone, but not with zolpidem. EEG power during NREM sleep increased in the delta band and decreased in the theta band following eszopiclone administration, whereas zolpidem had no effect on any of the frequency bands analyzed. Conclusions In aged as well as adult guinea pigs, eszopiclone is a more effective hypnotic insofar as it produces a shorter latency to NREM sleep, a greater amount of NREM sleep and EEG delta waves. Differences in the effects produced by eszopiclone and zolpidem as a function of the aging process likely reflect the fact that they bind to different subunits of the GABA A receptors, which are differentially reactive to the aging process.

Effects of eszopiclone and zolpidem on sleep–wake behavior, anxiety-like behavior and contextual memory in rats

“…For example, in adult rats, intraperitoneal administration of zopiclone in doses ranging from 2.5 to 10 mg/kg was found to decrease W, decrease latency of SWS, increase total amount of time spent in SWS, increase the latency of REM sleep, and decrease the total amount of time spent in REM sleep [34, 35, 95]. Similarly in the guinea pigs, intraperitoneal administration of 1, 3, and 10 mg/kg doses of eszopiclone were shown to decrease W and the latency of SWS and to increase the total amount of time spent in SWS [110, 111]. These two studies reported that the administration of eszopiclone increases the latency of REM sleep but did not reduce the total amount of time spent in REM sleep over a period of 2 h. Like these animal studies, Zopiclone has been shown in humans to shorten sleep latency and increase total sleep [40, 87].…”

“…The same study further reported that the administration of zolpidem at 7.5 mg/kg dose increased latency and decreased amount of time spent in REM sleep. However, in adult guinea pigs intraperitoneal administration of zolpidem at 3 and 10 mg/kg doses was found to decrease the amount of time spent in W and increase the amount of time spent in SWS but not the REM sleep [110, 111]. Like these animal studies, studies in human subjects have shown that zolpidem, in doses between 5 and 20 mg, shortens the latency to non-REM sleep and also increases the total amount of non-REM sleep [1, 88, 107].…”

“…Some other animal and human studies have also reported the effects of eszopiclone and zolpidem on the cortical EEG power. For example, in guinea pigs, administration of eszopiclone at 1 and 3 mg/kg doses was reported to increase spectral power in the delta band and to decrease in the theta band during SWS, but not during the W or REM sleep [110, 111]. These studies have also reported that the application of 1, 3, and 10 mg doses of zolpidem do not change the power of delta or theta bands in the cortical EEG during W, SWS, or REM sleep periods.…”

“…The doses of both drugs were 1, 3, and 10 mg/kg. These doses were predetermined based on previous studies to determine the effects of zopiclone, eszopiclone, and zolpidem on sleep-wake behavior in guinea pigs [110, 111] and rats [34, 35]. All drugs were injected i.p.…”

“…In recent years, a number of studies in both humans [24, 28, 40, 47–49, 62, 63, 82] and animals [10, 34, 35, 54, 64, 95, 110, 111] have tested the hypnotic effects of eszopiclone and zolpidem. These studies have suggested that both eszopiclone and zolpidem are nearly equally effective hypnotics with very few or no adverse side effects.…”