Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic

Noguchi, Hideaki; Kitazumi, Kazuhiro; Mori, Megumi; Shiba, Tadayoshi

doi:10.1016/s0014-2999(01)01502-3

Cited by 29 publications

(30 citation statements)

References 25 publications

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“…showed almost equal potency in increasing the delta wave activity with zaleplon (1 mg / kg, i.v.) in spectral analysis (2). The doses used in the study show a comparable effect as the therapeutic dosages.…”

Section: Discussionmentioning

confidence: 70%

“…induced a drowsiness reflected on spontaneous EEG (2). The pattern, indicative of hypnotic action, was characterized by high voltage slow waves in the cortical EEGs and desynchronization of the hippocampal theta waves.…”

Section: Discussionmentioning

confidence: 99%

“…demonstrate equivalent potency with zaleplon (1 mg / kg, i.v.) with regard to increasing the delta wave activity (2). Thus, in the present study, we investigated the effect of zaleplon on melatonin secretion in rabbits in comparison with the effect of triazolam and zopiclone under the same conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Zaleplon (N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide, CL284,846), a pyrazolopyrimidine derivative, displaces [ 3 H]flunitrazepam from neuronal binding sites in vitro and enhances the binding of t-butylbicyclophosphorothionate, a compound known to bind to a site affiliated with the benzodiazepine / GABA receptor complex (1,2). Pharmacokinetic studies on zaleplon indicate a plasma t max and an elimination t 1 / 2 , both, of about 1 h (3).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Noguchi¹,

Kitazumi²,

Mori³

et al. 2003

J Pharmacol Sci

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Abstract. Melatonin, a major hormone secreted by the pineal gland, is known to play an important role in regulation of the circadian rhythm. (N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (zaleplon) is a non-benzodiazepine hypnotic that acts via the benzodiazepine site of the GABA A receptor. In the present study, we investigated the effect of zaleplon on melatonin secretion in rabbits using RIA and compared the effect to triazolam and zopiclone. Zaleplon increased a dose-dependent concentration of melatonin in rabbit plasma collected at 30 min after intravenous administration at doses of 1 and 2 mg / kg. The zaleploninduced increase in plasma melatonin level was not blocked by flumazenil, a benzodiazepinereceptor antagonist. In contrast, triazolam and zopiclone failed to affect the plasma melatonin level. We also investigated the effect of zaleplon on intracellular cAMP in rat pinealocytes. Consequently, zaleplon had no effect on the intracellular cAMP levels in rat pinealocytes. These results of the present studies suggest that zaleplon may promote melatonin secretion and the elevation of plasma levels of melatonin may suggest an influence of zaleplon on chronobiology.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Noguchi¹,

Kitazumi²,

Mori³

et al. 2003

J Pharmacol Sci

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“…Zaleplon (N-[3-(3-cyanopyrazolo [1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide), a pyrazolopyrimidine, is a non-benzodiazepine sedativehypnotic. A benzodiazepine receptor binding assay suggested that zaleplon is a selective full agonist of the w 1 -receptor subtype within the g-aminobutyric acid (GABA) A receptor ionophore complex in the brain, enhancing the function of GABA as a result of an allosteric interaction with the GABA A -receptor chloride anion channel complex (3). It has been reported that zaleplon, although not benzodiazepine-like in chemical structure, induces sedative-hypnotic, anticonvulsant and anticonflict effects mediated by its binding to the central nervous system (CNS) type benzodiazepine receptors (4 -6).…”

Section: Introductionmentioning

confidence: 99%

Electroencephalographic Properties of Zaleplon, a Non-Benzodiazepine Sedative/Hypnotic, in Rats

Noguchi¹,

Kitazumi²,

Mori³

et al. 2004

J Pharmacol Sci

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Abstract. The encephalographic (EEG) properties of zaleplon were investigated in comparison with those of other sedative hypnotics in conscious rats with chronically implanted electrodes. The oral administration of zaleplon (0.25 -1.0 mg / kg), triazolam (0.0625 -0.25 mg / kg), zopiclone (1.0 -4.0 mg/ kg), brotizolam (0.0625 -0.25 mg / kg), and nitrazepam (0.125 -0.5 mg / kg) lengthened the total sleep in a dose-dependent manner. On distribution of sleep-wakefulness stages, zaleplon, in particular, increased the slow wave deep sleep (SWDS), whereas triazolam, brotizolam, and nitrazepam increased the slow wave light sleep (SWLS) in a dose-dependent manner. Zopiclone significantly increased the SWDS at a dose of 2 mg / kg and both the SWLS and the SWDS at a dose of 4 mg / kg. All tested hypnotics caused no influence on fast wave sleep (FWS) at doses tested. The appearance of the sleep-inducing activity of zaleplon was more rapid than those of any compounds tested, and zaleplon significantly increased the relative EEG power density in the delta frequency band over that of triazolam at 20 and 30 min after the administration in the spectral analysis. Therefore, the present findings suggest that the non-benzodiazepine zaleplon can be expected to exhibit high practical potential as a hypnotic and is characterized by an increase in SWDS with rapid onset of hypnotic action.

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Anti‐HAV Activity of Some Newly Synthesized Triazolo[4,3‐b]pyridazines

Shamroukh¹,

Ali

2008

Archiv der Pharmazie

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6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazine-3(2H)-thione 2 was used as precursor for the preparation of some novel 3-S-substituted-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazine derivatives 3-11. Furthermore, the preparation of 1-[2-(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-acetyl]-1H-pyrazole derivative 13 and 5-(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanylmethyl)-[1,3,4]oxadiazole derivatives 15 and 17, are described. Some of the prepared products revealed a promising antiviral activity against hepatitis-A virus (HAV, MBB-cell culture adapted strain). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with the test compounds. Compound 15 showed the highest effect on HAV compared to the other tested compounds.

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Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic

Cited by 29 publications

References 25 publications

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Effect of Zaleplon, a Non-benzodiazepine Hypnotic, on Melatonin Secretion in Rabbits

Electroencephalographic Properties of Zaleplon, a Non-Benzodiazepine Sedative/Hypnotic, in Rats

Anti‐HAV Activity of Some Newly Synthesized Triazolo[4,3‐b]pyridazines

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