Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats.
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.
Katoh
A
A
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Eigyo
M
M
Ishibashi
C
C
Naitoh
Y
Y
Takeuchi
M
M
Ibii
N
N
Ikeda
M
M
Matsushita
A
A
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D000068736:Duloxetine Hydrochloride; D004569:Electroencephalography; D005143:Eyelids / Q000187:drug effects; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D012472:Salivation / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013666:Tears; D013876:Thiophenes / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced
D006916:5-Hydroxytryptophan; D018759:Adrenergic Uptake Inhibitors; D000639:Amitriptyline; D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride; D008376:Maprotiline; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes