| Indication |
Milnacipran is used to treat moderate to severe clinical depression but this indication is not yet FDA-approved in the USA. Milnacipran is labelled for the treatment of fibromyalgia pain. |
| Mechanism of action |
Milnacipran inhibits norepinephrine and serotonin reuptake in a 3:1 ratio, in practical use this means a balanced (equal) action upon both transmitters. The serotonin reuptake inhibition is likely to improve depression, while the norepinephrine reuptake inihibition probably improves chronic pain. Milnacipran exerts no significant actions on postynaptic H1, alpha-1, D1, D2, and muscarinic receptors, as well as on benzodiazepine/opiate binding sites. [Wikipedia] |
| Absorption |
Milnacipran is well absorbed following oral administration with an absolute bioavailability of 85-90%. Meals have no effect on absorption. Peak concentrations occur 2 -4 hours post-administration and is delayed in elderly patients.
Time to steady state = 36 - 48 hours; |
| Protein binding |
Plasma protein binding is 13%. |
| Biotransformation |
Hepatic metabolism of milnacipran occurs via glucuronidation. No involvement of CYP450 isozymes or active metabolites found. |
| Route of elimination |
It is excreted predominantly unchanged in urine (50%- 60%, 24% as l-milnacipran and 31% as d-milnacipran). The l-milnacipran carbamoyl-O-glucuronide was the major metabolite excreted in urine and accounted for approximately 17% of the dose; approximately 2% of the dose was excreted in urine as d-milnacipran carbamoyl-O-glucuronide. Approximately 8% of the dose was excreted in urine as the N-desethyl milnacipran metabolite. |
| Toxicity |
LD50, oral, rat: 213 mg/kg. The most frequently occurring adverse reactions (>= 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth, and hypertension. |
| Affected organisms |
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