Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity.

Article Details

Citation

Copy to clipboard

Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ

Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity.

Biol Psychiatry. 2004 Feb 1;55(3):320-2.

PubMed ID

14744476 [ View in PubMed

]

Abstract

BACKGROUND: Though selective serotonin reuptake inhibitors have revolutionized the field of psychiatry with demonstrated efficacy in affective and anxiety disorders with minimal side effects, norepinephrine-serotonin reuptake inhibitors may provide efficacy similar to tricyclic antidepressants without the adverse side effects associated with tricyclic antidepressants. METHODS: The affinity and selectivity of milnacipran, duloxetine, venlafaxine, citalopram, amitriptyline, and nortriptyline were determined for the human serotonin, norepinephrine, and dopamine transporters. RESULTS: Both milnacipran and duloxetine were potent inhibitors of serotonin and norepinephrine uptake. Unlike duloxetine and venlafaxine, milnacipran appears serotonin transporter selective in binding (ratio = 2.61) and norepinephrine transporter selective in uptake (ratio =.45). CONCLUSIONS: Milnacipran's binding and uptake inhibition profile more closely resembles that of the tricyclic antidepressants than that of duloxetine. Whether these differences observed in vitro manifest themselves in vivo is not clear.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amitriptyline	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details
Amitriptyline	Sodium-dependent serotonin transporter	Protein	Humans	Yes	Inhibitor	Details
Duloxetine	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details
Duloxetine	Sodium-dependent serotonin transporter	Protein	Humans	Yes	Inhibitor	Details
Nortriptyline	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details
Nortriptyline	Sodium-dependent serotonin transporter	Protein	Humans	Yes	Inhibitor	Details
Venlafaxine	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Amitriptyline	Sodium-dependent noradrenaline transporter	Ki (nM)	63	N/A	N/A	Details
Amitriptyline	Sodium-dependent noradrenaline transporter	Ki (nM)	13.3	N/A	N/A	Details
Amitriptyline	Sodium-dependent serotonin transporter	Ki (nM)	3.45	N/A	N/A	Details
Citalopram	Sodium-dependent serotonin transporter	Ki (nM)	19	N/A	N/A	Details
Citalopram	Sodium-dependent serotonin transporter	Ki (nM)	1.13	N/A	N/A	Details
Milnacipran	Sodium-dependent noradrenaline transporter	Ki (nM)	68	N/A	N/A	Details
Milnacipran	Sodium-dependent noradrenaline transporter	Ki (nM)	22	N/A	N/A	Details
Milnacipran	Sodium-dependent serotonin transporter	Ki (nM)	151	N/A	N/A	Details
Milnacipran	Sodium-dependent serotonin transporter	Ki (nM)	8.44	N/A	N/A	Details
Nortriptyline	Sodium-dependent noradrenaline transporter	Ki (nM)	8.3	N/A	N/A	Details
Nortriptyline	Sodium-dependent noradrenaline transporter	Ki (nM)	1.49	N/A	N/A	Details
Nortriptyline	Sodium-dependent serotonin transporter	Ki (nM)	18	N/A	N/A	Details
Nortriptyline	Sodium-dependent serotonin transporter	Ki (nM)	317	N/A	N/A	Details
Venlafaxine	Sodium-dependent dopamine transporter	Ki (nM)	6050	N/A	N/A	Details
Venlafaxine	Sodium-dependent dopamine transporter	Ki (nM)	3070	N/A	N/A	Details
Venlafaxine	Sodium-dependent noradrenaline transporter	Ki (nM)	1420	N/A	N/A	Details
Venlafaxine	Sodium-dependent noradrenaline transporter	Ki (nM)	1920	N/A	N/A	Details
Venlafaxine	Sodium-dependent serotonin transporter	Ki (nM)	145	N/A	N/A	Details
Venlafaxine	Sodium-dependent serotonin transporter	Ki (nM)	7.8	N/A	N/A	Details