title: Pharmacodynamic effects of the sleep inducer zopiclone.
abstract: Pharmacodynamic effects of [6-(5-chloro-2-pyridyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin -5- yl]-4-methyl-1-piperazine-carboxylate (zopiclone, RP-27267), chemically unrelated to benzodiazepines and a potential new sleep inducer, on the peripheral system were investigated in several species of animals. The drug was dissolved in the vehicle of 0.01 mol/l HCl solution for intravenous administration or for addition to the bath medium and was suspended in 0.25% carboxymethylcellulose solution for oral administration. In unanesthetized rabbits, zopiclone, 0.5 mg/kg i.v., exerted no action and at 1 mg/kg slightly decreased respiration and heart rate without affecting blood pressure and ECG. Zopiclone at 10(-6) g/ml had no action in the isolated guinea-pig atria but at 10(-5) g/ml it produced a gradual and slight decrease in heart rate without affecting the contraction. In the isolated small intestine of rabbits and guinea-pigs, zopiclone at 10(-6) g/ml had no action but produced a slight inhibition in a dose of 10(-5) g/ml. Zopiclone, 10(-5) g/ml, did not affect the stimulatory effects of acetylcholine, serotonin, histamine and barium in the isolated guinea-pig intestine. Zopiclone, 1, 5 and 10 mg/kg i.v., exerted no action on rabbit intestinal movement in vivo. Zopiclone, 5, 10, 20 and 50 mg/kg p.o., had no effect on the propulsive motility of the mouse intestine. Zopiclone, 10(-5) g/ml, did not affect contractile movement of the uterus isolated from rabbits and did not influence the contractile response to epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tokunaga
authors.forename: H
authors.initials: H
authors.lastname: Morishita
authors.forename: K
authors.initials: K
authors.lastname: Kushiku
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: J
authors.initials: J
authors.lastname: Matsuki
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Kawamoto
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D053961:Azabicyclo Compounds; D001794:Blood Pressure / Q000187:drug effects; D003964:Diaphragm / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D014132:Trachea / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone