Pharmacodynamic effects of the sleep inducer zopiclone
Tokunaga, T.; Morishita, H.; Kushiku, K.; Abe, M.; Matsuki, J.; Inoue, T.; Kawamoto, H.; Furukawa, T.
Arzneimittel-Forschung 37(12): 1340-1345
1987
ISSN/ISBN: 0004-4172 PMID: 3449060 Document Number: 302793
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 of 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. In the in vivo uterine contractile movement of non-pregnant and pregnant rabbits, zopiclone, 5 and 10 mg/kg i.v., exerted little or no action, preceded by a slight temporary inhibition or excitation. In the isolated guinea-pig trachea, zopiclone, 10-5 g/ml, had no action and did not alter the stimulatory effect of acetylcholine or the inhibitory effect of isoprenaline. Zopiclone did not exert actions in the isolated guinea-pig vas deferens at 10-5 g/ml and did not influence the stimulatory effects of norepinephrine. Zopiclone, 10-6 and 10-5 g/ml, induced no alteration in the twitch tension of rat diaphragm. Zopiclone, 1 mg/kg i.v., had no effect on the bile outflow in rabbits, and doses of 10-6 and 10-5 g/ml did not evoke hemolysis. In conclusion, zopiclone exerts weak actions on peripheral systems.