Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 272; no. 3; pp. 1067 - 1075
• Main Authors: Katoh, A, Eigyo, M, Ishibashi, C, Naitoh, Y, Takeuchi, M, Ibii, N, Ikeda, M, Matsushita, A
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.03.1995
• Subjects: 5-Hydroxytryptophan - pharmacology; Adrenergic Uptake Inhibitors - pharmacology; Amitriptyline - pharmacology; Animals; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Body Temperature Regulation - drug effects; Duloxetine Hydrochloride; Electroencephalography; Eyelids - drug effects; Male; Maprotiline - pharmacology; Mice; Rats; Rats, Wistar; Rodentia; Salivation - drug effects; Serotonin Uptake Inhibitors - pharmacology; Tears; Thiophenes - pharmacology; Tremor - chemically induced
• ISSN: 0022-3565; 1521-0103

Duloxetine is a dual inhibitor of norepinephrine and serotonin reuptake. Duloxetine (3.13-50 mg/kg p.o.) significantly prevented tetrabenazine (1 and 50 mg/kg s.c.)-induced ptosis in mice and rats. Moreover, duloxetine (1.56-12.5 mg/kg p.o.) also inhibited reserpine (1 mg/kg s.c.)-induced hypothermia in mice. When duloxetine (12.5-100 mg/kg p.o.) and 5-hydroxytryptophan (80 and 100 mg/kg i.p.), a precursor of serotonin, were administered simultaneously to mice and rats, head movement behavior and tremor were observed. In addition, duloxetine (25-100 mg/kg p.o.) significantly attenuated immobility in forced swimming in mice, as equally effective as commonly used antidepressant drugs. Duloxetine (12.5-25 mg/kg p.o.) significantly decreased rapid eye movement sleep and slow-wave deep sleep and increased the awake period, as shown in the rat EEG. However, duloxetine (25-200 mg/kg p.o.) did not affect salivation and lacrimation induced by oxotremorine (1 mg/kg s.c.), a cholinergic agonist, whereas it (25-50 mg/kg) reduced the oxotremorine-induced tremor in part. These results indicated that duloxetine produced behavioral and electroencephalographic responses resulting from the inhibition of norepinephrine and serotonin reuptake in vivo, and that it had a weak anticholinergic action. Therefore, duloxetine may be clinically useful as an antidepressant.