Дулоксетин

Antidepressant.

Duloxetine (Cymbalta) is a newer antidepressant. It islargely like venlafaxine, which is an SNERI (selective norepinephrinereuptake inhibitor).

Duloxetine appears to be fairly well absorbed after oral doses, with peak plasma levels in 6 to 10 hours and linear pharmacokinetics. The drug is extensively metabolized in the liver to active metabolites, with 72% of an oral dose primarily excreted in the urine as conjugated metabolites and up to 15% appearing in the feces.
N-demethylation to an active metabolite (CYP2D6) and hydroxylation of the naphthyl ring (CYP1A2) at either the 4-, 5-, or 6-positions are the main metabolic pathways for duloxetine. Its metabolites are primarily excreted into the urine as glucuronide, sulfate, and O-methylated conjugation products. The major metabolites found in plasma also were found in the urine. Preclinical data for 4-hydroxyduloxetine suggests it has a similar pharmacological profile to duloxetine, with selective inhibition of SERT but less activity at the NET.

Duloxetine has been approved for the treatment of depression and diabetic peripheral neuropathic pain. It is another analogue in the line of fluoxetine-based products from Lilly, in which the phenyl and phenoxy groups of fluoxetine have been respectively replaced with the benzene isostere, thiophene, and a naphthyloxy group (previously described under fluoxetine). Duloxetine exhibits dual inhibition with high affinity for the SERTs and NETs, with a five times preferential inhibition of the SERT. Duloxetine appears to be a more potent in vitro blocker of SERTs and NETs than venlafaxine. In humans, duloxetine has a low affinity for the other neuroreceptors, suggesting low incidence of unwanted adverse effects.