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Katoh, A. et al.

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.[1]

References

Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats. Katoh, A., Eigyo, M., Ishibashi, C., Naitoh, Y., Takeuchi, M., Ibii, N., Ikeda, M., Matsushita, A. J. Pharmacol. Exp. Ther. (1995) [Pubmed]

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