Tags

Type your tag names separated by a space and hit enter

Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex.
J Pharmacol Exp Ther. 1995 Jan; 272(1):177-83.JP

Abstract

The effects of duloxetine (LY248686), a new inhibitor of serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine (NE) uptake on extracellular levels of NE, 5-HT and dopamine (DA), were studied in the rat frontal cortex and nucleus accumbens, using in vivo microdialysis. The oral administration of duloxetine (3.125-12.5 mg/kg) produced a dose-dependent increase in the output of both NE and 5-HT from the frontal cortex, this increase being maintained throughout the 4-hr observation period. Chronic administration of duloxetine (6.25 mg/kg, p.o.) for 14 days failed to alter basal NE and 5-HT levels in the frontal cortex, but augmented the duloxetine-induced increase in output of NE and 5-HT. Amitriptyline and maprotiline, administered p.o. at doses of 6.25 to 25 mg/kg, increased NE output, but the effect was weaker than that of duloxetine, and neither amitriptyline nor maprotiline changed 5-HT output from the frontal cortex. Duloxetine, amitriptyline, and maprotiline brought about increases in DA levels in the rat frontal cortex, the increase in DA levels induced by duloxetine being approximately two or three times more potent than that induced by amitriptyline and maprotiline. In the nucleus accumbens, duloxetine also produced a dose-dependent increase in DA output more potent than that produced by amitriptyline and maprotiline. These results show that duloxetine causes a potent and sustained increase in the output of both NE and 5-HT in the rat frontal cortex, related to its inhibition of NE and 5-HT uptake; these results also show that duloxetine increases DA output in the frontal cortex.

Authors+Show Affiliations

Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7815331

Citation

Kihara, T, and M Ikeda. "Effects of Duloxetine, a New Serotonin and Norepinephrine Uptake Inhibitor, On Extracellular Monoamine Levels in Rat Frontal Cortex." The Journal of Pharmacology and Experimental Therapeutics, vol. 272, no. 1, 1995, pp. 177-83.
Kihara T, Ikeda M. Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex. J Pharmacol Exp Ther. 1995;272(1):177-83.
Kihara, T., & Ikeda, M. (1995). Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex. The Journal of Pharmacology and Experimental Therapeutics, 272(1), 177-83.
Kihara T, Ikeda M. Effects of Duloxetine, a New Serotonin and Norepinephrine Uptake Inhibitor, On Extracellular Monoamine Levels in Rat Frontal Cortex. J Pharmacol Exp Ther. 1995;272(1):177-83. PubMed PMID: 7815331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex. AU - Kihara,T, AU - Ikeda,M, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 177 EP - 83 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 272 IS - 1 N2 - The effects of duloxetine (LY248686), a new inhibitor of serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine (NE) uptake on extracellular levels of NE, 5-HT and dopamine (DA), were studied in the rat frontal cortex and nucleus accumbens, using in vivo microdialysis. The oral administration of duloxetine (3.125-12.5 mg/kg) produced a dose-dependent increase in the output of both NE and 5-HT from the frontal cortex, this increase being maintained throughout the 4-hr observation period. Chronic administration of duloxetine (6.25 mg/kg, p.o.) for 14 days failed to alter basal NE and 5-HT levels in the frontal cortex, but augmented the duloxetine-induced increase in output of NE and 5-HT. Amitriptyline and maprotiline, administered p.o. at doses of 6.25 to 25 mg/kg, increased NE output, but the effect was weaker than that of duloxetine, and neither amitriptyline nor maprotiline changed 5-HT output from the frontal cortex. Duloxetine, amitriptyline, and maprotiline brought about increases in DA levels in the rat frontal cortex, the increase in DA levels induced by duloxetine being approximately two or three times more potent than that induced by amitriptyline and maprotiline. In the nucleus accumbens, duloxetine also produced a dose-dependent increase in DA output more potent than that produced by amitriptyline and maprotiline. These results show that duloxetine causes a potent and sustained increase in the output of both NE and 5-HT in the rat frontal cortex, related to its inhibition of NE and 5-HT uptake; these results also show that duloxetine increases DA output in the frontal cortex. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7815331/Effects_of_duloxetine_a_new_serotonin_and_norepinephrine_uptake_inhibitor_on_extracellular_monoamine_levels_in_rat_frontal_cortex_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7815331 DB - PRIME DP - Unbound Medicine ER -