Zopiclone

[Medical management of glaucoma and interaction between glaucoma and systemic medications].[Pubmed:30932874]

Laeknabladid. 2019 Apr;105(4):163-169.

INTRODUCTION: Glaucoma used to be the most common cause for blindness in Iceland. As the incidence of glaucoma increases with age, the patients often have numerous comorbidities and use various medications. It is important to keep in mind interactions and side effects of glaucoma medications when deciding systemic medical treatment for these patients to ensure their safety and comfort. The goal of the study was to gather information about drug use of patients with severe glaucoma. METHODS: A retrospective study where data were collected from 100 consecutive patients who underwent a trabeculectomy as first glaucoma surgery at Landspitali National University Hospital of Iceland during 2013-2017. All systemic and ophthalmic medications during 6 months before and after the surgery, medical diagnoses, age and gender of the patients were registered. RESULTS: Of all 100 patients, 87 used systemic medication, averaging 5.3 drugs/patient. Mean number of glaucoma medication used was 3.0. Mean age at surgery was 75 years and 53 were women. The most common systemic drug class was anti-hypertensives, used by 57 patients where beta-blockers were the most common, used by 30 patients. Zopiclone was the most common single drug, used by 29 patients. CONCLUSION: It is evident that patients with glaucoma take various drugs for systemic illness that can affect their glaucoma and have interactions with glaucoma drugs. It is urgent that healthcare providers keep this in mind when deciding on systemic treatment for patients with glaucoma, with regards to possible interactions with glaucoma drugs and the effect on patient's overall health.

Detection Time of Oxazepam and Zopiclone in Urine and Oral Fluid after Experimental Oral Dosing.[Pubmed:30615130]

J Anal Toxicol. 2019 Jan 7. pii: 5274652.

Data from previous experimental studies on the detection time of oxazepam and Zopiclone in biological matrices are limited. The aim of this study was to examine the detection time in urine and oral fluid after single oral doses of oxazepam and Zopiclone. Ten healthy volunteers received 25 mg of oxazepam in the evening of Day 1 and 7.5 mg of Zopiclone in the evening of Day 3. Urine and oral fluid samples were collected twice daily for 9 days, with an additional sampling the day after ingestion of Zopiclone. A total of 19 samples of both urine and oral fluid from each participant were analyzed using fully validated chromatographic methods. The median detection time for oxazepam was 91 h (range 73-108) in urine and 67 h (range 50-98) in oral fluid. The median detection time for Zopiclone in urine was 49 h (range 25-98) and 59 h (range 48-146) in oral fluid. The metabolite Zopiclone N-oxide showed a detection time of 36 h (range 25-84) in urine. The area under the concentration-time curve (AUCTotal) in urine corrected for creatinine was 150 mumol/L/mmol/L*h (range 105-216) for oxazepam and 1.60 mumol/L/mmol/L*h (range 0.79-4.53) for Zopiclone. In oral fluid, the AUCtotal was 673 nmol/L*h (range 339-1,316) for oxazepam and 2,150 nmol/L*h (range 493-4,240) for Zopiclone. In conclusion, oxazepam can be detected longer in urine than in oral fluid, while Zopiclone can be detected longer in oral fluid than in urine. The high AUCTotal for Zopiclone in oral fluid shows that the transfer into oral fluid is significant. In certain individuals the detection time of Zopiclone in oral fluid is long. These results can be helpful when interpreting drug testing analyzes.

Heterogeneous distribution of benzodiazepine receptors among rat neostriatal neurones.[Pubmed:8762113]

Br J Pharmacol. 1996 Jun;118(3):820-5.

1. The effects of benzodiazepine receptor (BZR) agonist were investigated in dissociated rat neostriatal neurones by a conventional whole-cell patch recording configuration at room temperature. 2. The dissociated neurones, with a longest somatic diameter of larger than 25 microns, were classified as 'large neurones', while those having soma measuring less than 15 microns were described as 'small neurones'. Large neurones were intensely positive for acetylcholinesterase staining, whereas the small ones were not. 3. CL218,872 enhanced the GABA response in both the large and small neurones with similar EC50S. However, the potentiation efficacy of CL218,872 in large neurones was larger than that of small ones. 4. Zolpidem also potentiated the GABA response in both neuronal populations with similar EC50S. This compound also enhanced the GABA response more strongly in large neurones than in small ones. 5. Zopiclone exerted a prominent potentiation in large neurones, although no difference was seen in the EC50S in the large and small neurones. 6. It was concluded that the BZR in large neurones had a different pharmacological property from that in small ones and that the BZR agonists showed a prominent difference, not in EC50, but in the potentiation efficacy between these neuronal populations.

Potentiation of gamma-aminobutyric acid-induced chloride currents by various benzodiazepine site agonists with the alpha 1 gamma 2, beta 2 gamma 2 and alpha 1 beta 2 gamma 2 subtypes of cloned gamma-aminobutyric acid type A receptors.[Pubmed:7901754]

Mol Pharmacol. 1993 Oct;44(4):866-70.

Previous studies with cloned gamma-aminobutyric acid type A receptors expressed in human embryonic kidney cells have indicated that the alpha 1 beta 2 gamma 2 and alpha 1 gamma 2 (but not alpha 1 beta 2) subtypes have benzodiazepine sites. We found in this study that even the beta 2 gamma 2 subtype displays gamma-aminobutyric acid-induced Cl- currents that are potentiated by triazolam (a triazolobenzodiazepine). The maximal efficacy of the drug among the subtypes was highest with the alpha 1 beta 2 gamma 2 subtype, followed by the alpha 1 gamma 2 and beta 2 gamma 2 subtypes. These observations led us to compare the ability of several benzodiazepine site agonists of diverse chemical structures to potentiate Cl- currents with these subtypes. With the alpha 1 gamma 2 subtype, diazepam, alpidem, zolpidem, Cl-218872, Zopiclone, U-79098 (an imidazoquinoxaline derivative), and U-90167 (a diimidazoquinazoline derivative) at 5 microM potentiated Cl- currents to essentially similar levels (slightly lower for a few ligands), compared with those with the alpha 1 beta 2 gamma 2 subtype. With the beta 2 gamma 2 subtype, the type 1 ligands zolpidem, alpidem, and Cl-218872 showed no or very low levels of potentiation, whereas less selective ligands such as diazepam, Zopiclone, U-78098, and U-90167 displayed levels of Cl- current potentiation comparable to those observed with the subtypes containing the alpha 1 and gamma 2 subunits. These data indicate that, in the presence of gamma 2, beta 2 may substitute for alpha 1 in forming the benzodiazepine site of limited sensitivity to the type 1 ligands. It appears that individual ligands for benzodiazepine sites have their own sets of interacting domains, which are distributed in alpha 1 and gamma 2, and the agonistic activity of type 1 ligands may be more dependent on the alpha 1-specific domains than is that of less selective ligands.

Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic.[Pubmed:2874974]

Drugs. 1986 Jul;32(1):48-65.

Zopiclone is the first of the cyclopyrrolones, a new class of psychotherapeutic agents possessing a pharmacological profile of high efficacy and low toxicity similar to that of the benzodiazepines. Binding is thought to occur to the benzodiazepine receptor complex, or to a site closely linked to this complex. Although Zopiclone exhibits anticonvulsant, muscle relaxant and anxiolytic properties in animals, it finds better use as an hypnotic because of marked sedating effects. In clinical trials, Zopiclone (usually 7.5 mg) improved sleep in chronic insomniacs similarly to nitrazepam 5 mg, flurazepam 15 to 30 mg, triazolam 0.5 mg and temazepam 20 mg, but in a single study was slightly less effective than flunitrazepam 2 mg in some evaluation criteria. Sleep induction before surgical procedures in hospitalised patients is satisfactory with Zopiclone, but when the drugs are administered a few hours before surgery, diazepam appears to be more effective in alleviating preoperative anxiety. Minimal impairment of psychomotor skills and mental acuity occurs in the morning after a bedtime dose of Zopiclone, which has a short half-life of about 5 hours and no long acting metabolites. No serious side effects have been reported in the relatively small number of patients studied to date; the development of 'bitter taste' does not deter patients from continuing therapy. Thus, with its short duration of action Zopiclone is a useful alternative to other hypnotics, especially in patients intolerant of residual effects the morning after taking an hypnotic.