Differences in pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics

doi:10.1016/0014-2999(90)90375-G

European Journal of Pharmacology

Volume 187, Issue 3, 23 October 1990, Pages 487-494

https://doi.org/10.1016/0014-2999(90)90375-G Get rights and content

Abstract

The hypnotics, quazepam (a benzodiazepine), brotizolam (a thienotriazolodiazepine), zopiclone (a cyclopyrrolone) and zolpidem (an imidazopyridine) have a common ability to bind to the benzodiazepine recognition site (ω receptor) within the GABA_A receptor. For this reason we compared their pharmacological profiles in mice. All compounds shared anticonvulsant and central depressant effects. However, the sedative activity of zolpidem appeared at much lower doses than did the anticonvulsant and myorelaxant effects but the opposite was observed with the other hypnotics. In contrast to brotizolam, quazepam and zopiclone, zolpidem did not increase food intake in mice placed in a novel environment, indicating that this drug lacks disinhibitory activity. Moreover the efficacy of zolpidem at the GABA_A receptor, as indicated by its activity against convulsions induced by the GABA synthesis inhibitor, isoniazid, was much greater than that of other hypnotics. These results suggest that the hypnoselective properties observed with zolpidem might be related to a high selectivity for the ω₁ recognition site of the GABA_A receptor coupled with a very high intrinsic activity.

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All hypnotics were generally well tolerated; there were no serious adverse side effects and no subjects discontinued the evaluations. Compared to placebo, zolpidem and rilmazafone had good results on the Functional Reach Test. Although subjective assessments tended to be poor in the early morning, rilmazafone significantly improved the body sway test in the other hypnotics.
A single dose of zolpidem 5 mg and triazolam 0.125 mg did not have any next-day residual effects on healthy elderly subjects. Residual effects appeared to be related to the compound's half-life and the dose used. Rilmazafone 1 mg exhibited steadiness in static and dynamic balance and seemed to be more favorable for the elderly with early morning awakening.
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Antiepileptic drugs have been reported to manifest signs of neurological deficit, such as sedation, ataxia, abnormal gait, reduced or inhibited righting reflexes, muscle relaxation and cognitive deficits (Loscher and Schmidt, 1988). Diazepam, which was used as standard, has been reported to produce neurological deficit in anticonvulsant dose (Perrault et al., 1990; Peterson, 1998). Medicinal plants have served as sources of readily accessible, inexpensive and effective medication since the earliest times known to man.
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Differences in pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics

Abstract

European J. Pharmacol.

European J. Pharmacol.

Life Sci.

Life Sci.

Life Sci.

Brain Res.

Life Sci.

J. Am. Pharmacol. Assoc.

Life Sci.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

European J. Pharmacol.

European J. Pharmacol.

Neuropharmacology

Neurosci. Lett.

Biochem. Pharmacol.

Pharmacol. Biochem. Behav.

European J. Pharmacol.

Pharmacological profile of the imidazopyridine zolpidem at benzodiazepine receptors and electrocorticogram in rats

Naunyn-Schmiedeb. Arch. Pharmacol.