What Is Zopiclone Withdrawal?
6- (5-chloropyridin-2-yl) -7-[(4-methylpiperazin-1-yl) carbonyloxy] -5,6-dihydropyrrole [3.4-b] pyrazine-5- ketone
- Zopiclone is used for insomnia caused by various reasons, especially for patients who cannot tolerate the residual effects of the next morning.
- Drug name
- Zopiclone
- Drug type
- Essential medicines
- English name
- Zopiclone
- Chinese alias
- Zolpidone; Pyrazine
- English alias
- Zimovane; RP-27267
Zopiclone chemical name
- 6- (5-chloropyridin-2-yl) -7-[(4-methylpiperazin-1-yl) carbonyloxy] -5,6-dihydropyrrole [3.4-b] pyrazine-5- ketone
Zopiclone molecular structure
Zopiclone molecular formula
- C17H17ClN6O3
Zopiclone molecular weight
- 388
Physicochemical Properties of Zopiclone
- It is white to light yellow crystalline powder. No odor, bitter taste, easily soluble in dimethyl sulfoxide or chlorine, more soluble in glacial acetic acid or anhydrous acetic acid, difficult to dissolve in methanol, acetonitrile, acetone or ethanol, extremely difficult to dissolve in ether or isopropanol, almost insoluble In the water.
Zopiclone Pharmacology
- It is a third-generation hypnotic drug of the cyclopyrrolidone class. It is an inhibitory neurotransmitter -aminobutyric acid (GABA) receptor agonist. Its structure is different from that of benzodiazepines. It is a cyclopyridone compound and binds to the same receptor and site as benzodiazepines. But it works in different areas. This product works quickly and has a stronger effect than benzodiazepines. Animal experiments have confirmed that in addition to hypnotic and sedative effects, this product also has anti-anxiety, muscle relaxation and anti-convulsant effects. This product is rapidly absorbed orally. It can reach the peak blood concentration after 1.5-2 hours after administration. The oral concentration is 7.5mg, the peak concentration is 64-86ng / ml, the oral bioavailability is 80%, and the plasma protein binding rate is 45%. This product is widely distributed in tissues, with a distribution volume of 100L. Through liver metabolism, the main metabolite is non-pharmacologically active N-methyl zopiclone. N-oxidation products have a certain pharmacological activity. Most drugs (about 80%) are excreted by the kidney in the form of metabolites. The elimination half-life is 5 to 6 hours.
Zopiclone indications
- For insomnia caused by various reasons, especially for patients who can not tolerate the residual effects of the next morning.
Zopiclone usage and dosage
- Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.
Zopiclone adverse reactions
- Adverse reactions include drowsiness, bitter mouth, dry mouth, muscle weakness, and headache; abrupt withdrawal after long-term medication can cause rebound insomnia, nightmares, nausea, vomiting, anxiety, myalgia, and tremor. Rarely, there are throbbing, muscle tremors, and confusion.
Zopiclone contraindications
- Prohibited in patients allergic to this product, respiratory decompensation and severe liver dysfunction. Not suitable for pregnant women, lactating women and children under 15 years.
Zopiclone considerations
- (1) Overdose of this product can cause deep sleep or even coma. (2) The medication should not be taken for too long, generally not more than 4 weeks, and can be used intermittently. Do not drive or engage in mechanical operations during medication. Gradually reduce the dose when stopping. (3) Drinking alcohol is prohibited during medication.
Zopiclone drug interactions
- (1) Combined with neuromuscular blockers and central nervous system inhibitors, the sedative effect is enhanced. (2) Metoclopramide increases the plasma concentration of zopiclone when combined. (3) When combined with carbamazepine, the peak concentration of zopiclone increased, while the peak concentration of carbamazepine decreased. (4) Erythromycin increases AUC and t1 / 2 of zopiclone with concomitant psychomotor disorders. (5) When combined with atropine and rifampicin, the concentration of zopiclone was reduced. (6) Combined with benzodiazepine hypnotics to increase withdrawal symptoms.
Zopiclone
- Tablet: 3.75mg, 7.5mg
Introduction to Zopiclone Pharmacopoeia
- [Identification] (1) Take about 0.1g of this product, add 2ml of hydroxylamine hydrochloride test solution, adjust the pH to 8 ~ 10 with 5mol / L alcohol-made potassium hydroxide solution, heat to boiling, and cool. After adding dilute hydrochloric acid to make it acidic, 2 drops of ferric chloride test solution was added dropwise, and the solution was purple-red. (2) Take this product, weigh it accurately, add 0.1 mol / L hydrochloric acid solution to make a solution containing 15 µg per 1 ml, and determine it by spectrophotometry (Chinese Pharmacopoeia 2000 Edition Two W Record IV A). There is maximum absorption at the wavelength, and the absorption coefficient (E1% 1cm) is 345 ~ 380. (3) The infrared absorption spectrum of this product should be the same as that of the control (pharmaceutical infrared spectrum set 755). [Check] Clarity and color of the solution. Take 0.50g of this product. After dissolving with 10.0ml of dimethylformamide, the solution should be clear and colorless; if it is cloudy, it should be mixed with No. 2 turbidity standard solution (Appendix B) of the Ministry of Pharmacy must not be thicker in comparison; if the color is developed, it must not be deeper compared with the yellow standard colorimetric solution No. 5 (Appendix A of the Second Edition of the Chinese Pharmacopoeia 2000 Edition). Chloride: Take 1.0g of this product, add 50ml of water, dissolve by ultrasound, filter, and take 25ml of the filtrate, check according to law (Chinese Pharmacopoeia 2000 Edition, Appendix II A), and compare with the control solution made from 5.00ml of standard sodium chloride , Must not be thicker (0.010%). Relevant substances take this product, add dioxane to make a solution containing 100mg per 1ml as the test solution; take a precise amount, and dilute with dioxane to make 0.1ml, 0.2mg, The 0.3 mg and 0.5 mg solutions were used as control solutions (1), (2), (3), and (4). According to the thin layer chromatography (Chinese Pharmacopoeia 2000 edition, Appendix VB) test. 10 l of each of the above five solutions was pipetted, and each was spotted on the same silica gel GF254 thin-layer plate, using chloroform-methanol-ethyl acetate (85: 10: 5) as a developing agent. After the development, it was dried and placed in an ultraviolet light (254nm). ). The solution of the test product is not more than 3 if there are spots of impurities. Compared with the main spots shown in the control solutions (1), (2), (3), (4), the total impurities must not exceed 0.5%. Chloroform, dioxane and dimethylformamide were accurately weighed 0.5g, and placed in a headspace sampling bottle, 10ml of dimethylsulfoxide was precisely added, shaken, sealed, and used as a test solution; An appropriate amount of chloroform, dioxane and dimethylformamide was added, dissolved in dimethylsulfoxide and quantitatively released into a solution containing 3µg of chloroform, 19µg of dioxane and 44µg of dimethylformamide per 1ml, and shaken. 10ml was accurately measured, placed in a headspace sampling bottle, sealed, and used as a reference solution. According to the Organic Solvent Residues Inspection Method (Chinese Pharmacopoeia 2000 Edition Appendix II P Second Method), a capillary column with a fixed solution of 6% cyanopropylbenzene 94% siloxane: programmed temperature increase. Initial temperature 40 ° C, After holding for 8.5 minutes, the temperature was raised to 5 ° C to 90 ° C per minute, and then to 20 ° C to 200 ° C per minute; the inlet temperature was 180 ° C; the detector temperature was 200 ° C; the headspace heating temperature was 100 ° C, and the headspace heating time 30 minutes. Record the chromatograms of the test solution and the reference solution, and calculate the peak area according to the external standard method. The content of chloroform shall not exceed 0.006%, the content of dioxane shall not exceed 0.038%, and the content of dimethylformamide shall not exceed 0.088%. Take this product for weight loss on drying, use phosphorus pentoxide as desiccant, and dry under reduced pressure to constant weight at 60 ° C, and the weight loss should not exceed 0.5% (Chinese Pharmacopoeia 2000 Version 2 Appendix L). Take 1.0g of this product and check it according to law (Appendix N of the Second Part of Chinese Pharmacopoeia 2000 Edition). The remaining residue should not exceed 0.1%. Take the residues left by the burning residue under heavy metals and inspect them in accordance with law (Chinese Pharmacopoeia 2000 Edition, Appendix II H Second Law). The content of heavy metals must not exceed 20 parts per million. [Content determination] Take about 0.3g of this product, accurately weigh, add 20ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and titrate with perchloric acid titration solution (0.1mol / L) under magnetic stirrer The solution turned blue and the results of the titration were corrected with a blank swab test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 38.88mg of C17H17Cl6O3. [Category] Hypnotics. [Storage] shading and sealed.