Article: Duloxetine

Duloxetine
Systematic (IUPAC) name
N-methyl-3-naphthalen-1-yloxy- 3-thiophen-2-yl-propan-1-amine
Identifiers
CAS number	136434-34-9
ATC code	N06AX21
PubChem	60835
DrugBank	APRD00060
Chemical data
Formula	C18H19NOS
Mol. weight	297.416 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	>90%
Metabolism	?
Half life	8-17 hours
Excretion	70% in urine, 20% in feces
Therapeutic considerations
Pregnancy cat.	C (USA)
Legal status	Prescription only (USA)
Routes	Oral

Duloxetine hydrochloride (brand names: Cymbalta/Yentreve) is a medically used drug that primarily targets major depressive disorders (MDD), pain related to diabetic peripheral neuropathy and stress urinary incontinence (SUI). Known also as LY248686, chemically (+)-(S)-N-methyl-3-(1-naphthyloxy)-2-thiophenepropanamine, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE and 5-HT transport sites. Its behavior contrasts to most other dual-reuptake inhibitors in that Ki values are nearly 1:1.

Furthermore, duloxetine lacks affinity for monoamine receptors within the central nervous system. While there is limited data available regarding the pharmacokinetic profile of duloxetine in humans, its half-life is reported to be 10 to 15 hours. Most common side effects in clinical trials were nausea, somnolence, and dry mouth. In clinical trials weight gain was neutral compared to placebo. Five people, including a 19-year old college student, committed suicide while Eli Lilly was conducting preliminary trials. [1] Ongoing studies including a 52 week safety and efficacy trial are available at www.lillytrials.com. Long-term side-effects seen in these trials did not vary from the original approval studies.

Duloxetine is approved by the FDA for the treatment of diabetic neuropathy. Approved dosages for treatment of diabetic peripheral neuropathic pain are 60 mg and 120 mg once daily.

When used for the treatment of depression, the approved dosage is 40 mg to 60 mg once daily. Duloxetine is available in capsules of 20 mg, 30 mg, and 60 mg.