Table 1.

Select Compounds in Development for Major Depressive Disorder^a

General Mechanism	Molecular Target	Compound	Pharmacodynamic Action	Sponsor	Development Phase
Monoaminergic	SERT, NET	Levomilnacipran	Reuptake Blockade	Forest Laboratories	Phase III
Monoaminergic	NET	LY2216684	Reuptake Blockade	Eli Lilly	Phase III
Monoaminergic	D2 Receptor	OPC-34712	Partial Agonist	Lundbeck	Phase III
Monoaminergic	SERT, Additional 5- HT Targets	Vortioxetine	Reuptake Blockade; Additional 5-HT Modulation	Lundbeck	Phase III
Monoaminergic	SERT, NET, DAT	EB-1010	Reuptake Blockade	Euthymics Bioscience	Phase II/III
Monoaminergic	SERT, NET, DAT	BMS-820836	Reuptake Blockade	Bristol-Myers Squibb	Phase II
Monoaminergic	SERT, Additional 5- HT Targets	TGBA01AD	Reuptake Blockade; Additional 5-HT Modulation	Fabre-Kramer Pharmaceuticals	Phase II
Monoaminergic	MAO-A	CX157	Reversible Enzyme Inhibitor	CeNeRx Pharma	Phase I
Monoaminergic	SERT	DSP-1053	Reuptake Blockade	Sunovion Pharmaceuticals	Phase I
Monoaminergic	SERT, NET, DAT	SEP-228432	Reuptake Blockade	Sunovion Pharmaceuticals	Phase I
Monoaminergic	SERT, NET, DAT	Tedatioxetine	Reuptake Blockade	Lundbeck	Phase I
Cholinergic	Muscarinic M1 Receptor	BCI-224	Partial Agonist	BrainCells	Phase I
Glutamatergic	NMDAR	AZD6765	Antagonist	AstraZeneca	Phase II
Glutamatergic	NMDAR	GLYX-13	Glycine-Site Partial Agonist	Naurex	Phase II
Glutamatergic	mGluR5	RG7090	Antagonist	Roche	Phase II
Glutamatergic	mGluR2/3R	BCI-632	Antagonist	BrainCells	Phase I
HPA Axis Modulation	Glucocorticoid Receptor	Mifepristone	Antagonist	Corcept Therapeutics	Phase III
HPA Axis Modulation	Vasopressin- 1b Receptor	ABT-436	Antagonist	Abbott Laboratories	Phase I
Neuropeptide	Galanin-3R	HT-2157	Antagonist	Dart NeuroScience	Phase I/II
Inflammatory Modulation	Erythropoietin Receptor	ARA290	Agonist	Araim Pharmaceuticals	Phase II
Neurotrophic	Hippocampal Neurogenesis	NSI-189	Unknown/Not Reported	Neuralstem	Phase I
Melatonin Modulation	Melatonin-1, Melatonin-2 Receptors	Tasimelteon	Agonist	Vanda Pharmaceuticals	Phase I/II

^aExamples of agents in the pharmaceutical development pipeline for major depressive disorder; Table organized by general mechanism and development phase. Information obtained from public sources, including the PhRMA Medicines in Development for Mental Illness Report 2012. DAT, dopamine transporter; HPA, hypothalamic–pituitary–adrenal; NET, norepinephrine transporter; NMDA, N-methyl-d-aspartate; NMDAR, NMDA receptor; MAOI, Monoamine oxidase inhibitor; RIMA, Reversible inhibitor of MAO-A; SERT, serotonin transporter