Pharmacology zopiclone

The cyclopyrrolone zopiclone was one of the first compounds other than the benzodiazepines to be shown to bind at the benzodiazepine receptor. More potent compounds have also been developed (e.g., suriclone and pagoclone). The cyclopyrrolones may actually bind to a different domain on the a subunit from the benzodiazepines (Canton and Doble 1992), and this may underlie the pharmacological differences seen in vivo, that is, lack of some side effects and lack of tolerance after long-term dosing. 

Lader M, Denney SC. A double-blind study to establish the residual effects of zopiclone on performance in healthy volunteers. Pharmacology 1983 27(suppl 2) 98-108. 

Zopiclone is available as a racemic mixture. Zopiclone, 7.5 mg administered orally at nighttime, is rapidly absorbed. It has a bioavailability of approximately 75 % and a time of occurrence of maximum plasma concentration (Cmax) of 1.6 hours [22, 23], The compound undergoes oxidation to the N-oxide metabolite, which is pharmacologically active, and demethylation to the inactive N-demethyl-zopiclone (Tab. 2). The elimination half-life (ti/2) of zopiclone and its active metabolite ranges from 3.5 to 6.0 h [24],... 

Gaillot J, Heusse D, Houghton D, Aurele JM, Dreyfus J (1983) Pharmacokinetics and metabolism of zopiclone. Pharmacology 27 (Suppl 2) 76-91... 

Noble S, Langtry HD, Lamb H M (1998) Zopiclone An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs 55 277-302... 

Mamelak M, Csima A, Price V (1983) Effects of zopiclone on the sleep of chronic insomniacs. Pharmacology 27 156-164... 

Petre Quadens O, Hoffman G, Buytaert G (1983) Effects of zopiclone as compared to flurazepam on sleep in women over 40 years of age. Pharmacology 27 (Suppl 2) 146-155... 

Jovanovic UJ, Dreyfuss JF (1983) Polygraphical sleep recording in insomniac patients under zopiclone or nitrazepam. Pharmacology 27 136-145... 

Dorian P, Sellers EM, Kaplan H (1983) Evaluation of zopiclone physical dependence liability in normal volunteers. Pharmacology 27, Suppl 2 228-234... 

Suriclone, a cyclopyrrolone analogue of zopiclone, has similar pharmacology to the benzodiazepines, binding close to the same site of the GABA receptor-chloride channel complex. It is effective as an anxiolytic and has the notable advantages of minimal sedation and cognitive toxicity, and milder withdrawal effects than those of diazepam or lorazepam (1). Its withdrawal from further development is a mystery. 

Although it is chemically distinct to the benzodiazepines, zopiclone, a cyclopyrrolone, has similar pharmacology, binding close to the same site of the GABA receptor-chloride channel complex. 

---