Ambien online research references
Neuropharmacology. 1987 Oct;26(10):1513-8.
Investigation of the development of tolerance to the actions of zolpidem and midazolam.
Sanger DJ, Zivkovic B.
Laboratories d'Etudes et de Recherches Synthelabo (L.E.R.S.), Bagneux, France.
It is well established that tolerance can develop very rapidly to the behaviour-suppressing effects of benzodiazepines. In previous studies, however, the depressant action of zolpidem, a novel hypnotic acting at the benzodiazepine receptor, on operant behaviour in rats was maintained after many injections. An experiment was carried out, therefore, to compare the effects of acute and chronic administration of zolpidem and midazolam. Rats were trained to press a lever in standard operant test chambers to obtain 45 mg food pellets on an FR 10 schedule. Dose-response curves were then established, before, immediately after and 4 weeks after the daily administration of midazolam (3.0 mg/kg s.c.) or zolpidem (1.0 mg/kg) for 10 days. In confirmation of previous work, marked tolerance developed to the response-rate-decreasing effect of midazolam, the dose-response curve being shifted to the right by a factor of 6 and also flattened. No significant dissipation of this tolerance occurred during a period of 4-6 weeks. In contrast, repeated administration of zolpidem produced only a small degree of tolerance, the dose-response curve being shifted by a factor of two. There was little evidence for cross tolerance between the two drugs, zolpidem-treated rats being sensitive to a dose of midazolam and midazolam-treated rats sensitive to a dose of zolpidem. Although the explanation for the development of tolerance to midazolam is unknown, these results suggest that the mechanisms of action of midazolam and zolpidem in reducing response rates are different.
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J Chromatogr. 1986 Nov 28;383(1):206-11.
High-performance liquid chromatographic determination of zolpidem, a new sleep inducer, in biological fluids with fluorimetric detection.
Guinebault P, Dubruc C, Hermann P, Thenot JP.
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Br J Clin Pharmacol. 1986 Feb;21(2):205-11.
Hypnotic activity of an imidazo-pyridine (zolpidem).
Nicholson AN, Pascoe PA.
Effects of an imidazo-pyridine (zolpidem: 10, 20 and 30 mg) on overnight sleep and on performance the next day were studied in young adults and in middle aged individuals. The young adults were used particularly as an homogenous group to establish any possible adverse effects of the drug on sleep and on performance the next day, and the middle aged subjects with their less restful sleep were used to study efficacy. In the young adults zolpidem led to a marked increase in slow wave sleep with a reduction in stage 2 sleep. There were no significant changes in REM sleep, though there was a tendency for REM sleep to be delayed. In the middle aged there was a reduction in awake activity and drowsy sleep with an increase in stage 2 sleep. The latency to REM sleep was increased but the duration of REM sleep over the whole night was not reduced. Digit symbol substitution and a complex reaction time task were used to study performance, but there were no residual effects with zolpidem (9 h after ingestion). Zolpidem is likely to prove useful in the management of transient and short-term insomnia in healthy middle aged individuals when impaired performance the next day is to be avoided.
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Psychopharmacology (Berl). 1995 Jun;119(4):399-404.
State-dependent effects of atypical benzodiazepine-receptor agonists.
Jackson A.
Merck Sharp and Dohme, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK.
The state-dependent effect of the BZ-receptor agonist diazepam (1.25-10 mg/kg), the partial agonist FG 8205 (0.5-4.0 mg/kg) and the BZ1-receptor agonist zolpidem (0.25-2 mg/kg) were investigated in rats. During daily sessions, animals were trained to acquire FR10 lever pressing for food reinforcement whilst under the influence of the agonists, using an operant technique. Forty-eight hours after the final training session under drug, their performance of the FR10 was evaluated during a test session, carried out following vehicle administration only. Neither diazepam, nor FG 8205 impaired acquisition of the task. In the group treated with 2 mg/kg zolpidem, six out of eight rats failed to learn within 20 sessions, but the smaller doses were without effect on acquisition. When drug treatment was withdrawn, there was evidence that all three of the agonists tested produced state-dependency. This was apparent in the form of longer latencies to obtain reinforcement and decreased lever pressing rates. The significance of these findings are discussed in the context of the relationship between the state-dependent effects of BZ-receptor agonists and their other properties, and the receptor subtypes which might underly these effects.
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Sleep. 1995 Jul;18(6):417-24.
Effects of bedtime administration of zolpidem on circadian and sleep-related hormonal profiles in normal women.
Copinschi G, Akseki E, Moreno-Reyes R, Leproult R, L'Hermite-Baleriaux M, Caufriez A, Vertongen F, Van Cauter E.
Center for Biological Rhythms, School of Medicine, Universite Libre de Bruxelles, Belgium.
Short-acting benzodiazepine hypnotics may phase-shift circadian rhythms and improve adaptation of sleep patterns to abrupt time shifts, depending on the timing of administration. The aim of the present study was to determine whether bedtime administration of zolpidem, a non-benzodiazepine hypnotic, causes alterations in circadian rhythmicity or in the normal interactions between sleep and hormones. Eight normal women (aged 21-33 years) each participated in a baseline study and a study with zolpidem administration. On each occasion, blood samples were obtained at 20-minute intervals for 25 hours, starting at 1000 hours. Zolpidem (10 mg) was given orally at 2245 hours. Zolpidem administration was associated with an increase in stages III + IV sleep. Cortisol, melatonin, thyrotropin and growth hormone profiles were similar in both experimental conditions. In contrast, though remaining in the normal range, the nocturnal elevation of prolactin was enhanced two-fold in all subjects after zolpidem during early sleep, and prolactin levels were still 50% higher than baseline in late sleep. Morning levels were similar in both studies. In conclusion, bedtime administration of 10 mg zolpidem, a standard clinical dosage, systematically induces a transient moderate hyperprolactinemia, but does not alter other sleep-related hormonal secretions or endocrine markers of circadian rhythmicity.
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