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Pharmacology and pharmacokinetics of milnacipran.
Puozzo C, Panconi E,
Deprez D.
IRPF Pierre Fabre Biomerieux,
Boulogne, France.
Int Clin Psychopharmacol. 2002 Jun;17 Suppl 1:S25-35.
Abstract
Milnacipran is a dual-action
antidepressant drug with equivalent inhibitory action at noradrenaline and
serotonin neuronal reuptake systems. This dual action has been
demonstrated in vitro and in vivo in experimental animals, and ex vivo in
man. Milnacipran has no relevant affinity for any neurotransmitter
receptor studied, in particular postsynaptic adrenergic, muscarinic and
histamine receptors, and is therefore expected to be devoid of the
prominent side-effects of many earlier antidepressants. Studies in human
volunteers have not demonstrated any impact of milnacipran on cognitive
function, consistent with its lack of anticholinergic properties. These
pharmacodynamic properties are well preserved in vivo in humans, because
milnacipran is only metabolized to a limited extent, and therefore
circulates in the body principally as the unchanged parent drug, which is
the only pharmacologically active compound at clinical doses. The
pharmacokinetic profile of milnacipran is characterized by rapid
absorption, high bioavailability, low protein binding, and rapid
elimination, both by hepatic glucuronidation and renal excretion. This
gives milnacipran certain pharmacokinetic advantages, such as low
inter-individual variation in plasma levels, low potential for drug
interactions, and limited impact on hepatic cytochrome P450 systems. These
pharmacokinetic properties differentiate milnacipran from most other
antidepressant drugs and contribute to the good safety profile of
milnacipran and allow it to be used simply and flexibly in clinical
practice.
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