Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD

This list was graciously provided by JR Becker (jrbecker76@hotmail.com). Some additions have been made by Shawn Thomas (shawn@neurotransmitter.net). Please send additions or corrections to jrbecker76@hotmail.com Information about recent drug approvals can be obtained from the FDA Center for Drug Evaluation and Research. For information about drugs already marketed in the US, see Neurotransmitter.net's Drug Reference for FDA Approved Psychiatric Drugs. A List of Drugs in Development for Neurodegenerative Diseases [PDF] compiled by Myoung-Ok Kwon and colleagues (2004) is available from the journal Neurodegenerative Diseases; 1(2-3):113–152. Please support the NIMH's GenRED (Genetics of Recurrent Early-onset Depression) study, the largest psychiatric genetics study ever attempted. Updated 12/03/07

Treatments for Depression and Anxiety
Drug Name Pharmacologic Action Company Indication Developmen tal Phase Links

Pristiq (DVS233 SR, desvenlafaxine )

Metabolite of Effexor (venlafaxine)

Wyeth

Depression, anxiety

Gepirone ER Saredutant (SR 48968) Valdoxan (agomelatine, AGO 178) Amibegron, SR 58611

5-HT1A partial agonist NK2 antagonist 5-HT2C antagonist, 5-HT2B antagonist, melatonin M1/M2 receptor agonist beta-3-adrenoceptor agonist

FabreKramer SanofiAventis Servier, Novartis

Depression, anxiety Depression, anxiety Depression, anxiety, sleep disorders Depression, anxiety

Approvable (but further needed Phase III trials suggest a 2008 approval date) Not Approvable Phase III EU: Resubmissio n planned in ’07. US: Phase III A supplement al NDA is possible in 2007 Phase III Phase III Phase II

[FabreKramer's Drug Profile] [Effects of SR 48968 on rodents] [Receptor activity] [Oct 2005 press release] [SR 58611 is a selective beta-3adrenoceptor agonist] [January 2007 Press Release]

SanofiAventis

Vilazodone Pexacerfont, BMS-562086 Lu AA21004

5-HT1A partial agonist, serotonin reuptake inhibitor CRF1 antagonist bis-aryl-sulphanyl modulator

Clinical Data Online, Inc. Bristol-Myers Squibb Lundbeck

Depression Depression, anxiety Depression, anxiety

Casopitant, GW679769 PRX-00023 Miraxion, LAX101 TIK-101 TGWOOAD/AA TGBA01AD GW372475, NS2359

NK1 antagonist 5-HT1A agonist, sigma receptor antagonist "Purified" Omega-3 [EPA] NMDA Antagonist 5-HT1A agonist, 5-HT2 antagonist Serotonin reuptake inhibitor, 5-HT2 agonist, 5-HT1A agonist, and 5-HT1D agonist Dopamine, serotonin, and norepinephrine, reuptake inhibitor

GSK Epix Amarin Tikvah Pharmaceuti cals FabreKramer FabreKramer GSK, NeuroSearch

Depression, anxiety, emesis Depression Huntington' s Disease, Depression Anxiety Anxiety Depression Depression

Phase II Phase II Phase II Phase II Phase II Phase II Phase II [FabreKramer's info] [FabreKramer's info] [Compound Profile]

Nemifitide (INN 00835)

Pentapeptide analog of melanocyte-inhibiting factor (MIF-1) administered intravenously (mechanism unknown)

Tetragenex

Depression

Phase II

[Innapharma' s info] [Antidepressa nt-like effects of a novel pentapeptide , nemifitide, in an animal model of depression] [MIF-1 may regulate ACTH secretion]

ORG 34517/34850 Vestipitant, GW597599 DOV 21, 947

GR antagonist NK1 antagonist Dopamine, serotonin, and norepinephrine, reuptake inhibitor

Organon GSK DOV/Merck

Depression Depression, anxiety Depression, ADHD, RLS Depression, ADHD Depression

Phase II Phase II Phase II [Antidepressa nt-like actions of DOV 21,947] [First Phase II Study]

LY2216684 YKP-10A, R228060

PD 332-334 Elzasonan, CP448,187

Norepinephrine reuptake Eli Lilly inhibitor Phenylalanine derivative with Janssen unknown mechanism (Johnson & Johnson)/SK Pharmaceuti cals Alpha2delta calcium channel Pfizer blocker 5-HT1B and 5-HT1D receptor Pfizer antagonist

Phase II Phase II

Anxiety Depression, anxiety

Phase II Phase II

[11/06 Pfizer Presentation]

Lu AA24530 SEP-225289 SSR149415

Multiple targets DA/NE/5-HT reuptake inhibitor V1B antagonist

Lundbeck

AZD6765 GW876008 ONO-2333Ms R-tofisopam GW823296 (orvepitant) Tyrima PRE703 Delucemine, NPS 1506 Lu AA34893 Lu AA44608 AFQ056

CRF1 antagonist CRF1 antagonist R-isomer of racemic tofisopam (a 2,3benzodiazepine) NK1 antagonist Reversible monoamine oxidase A (MAO-A) inhibitor MgluR agonist NMDA antagonist

Depression, anxiety Sepracor Depression, anxiety SanofiDepression, Aventis anxiety, hyperphagi a AstraZeneca Depression, anxiety Neurocrine/G Depression, SK anxiety, IBS Ono Depression, Pharmaceuti anxiety cals Pharmos Anxiety, IBS GSK CeNeRx Prescient NPS Depression, anxiety Depression, anxiety Anxiety Depression, stroke Depression, anxiety Depression, anxiety Anxiety

Phase II Phase I Phase II [SSR149415 review]

Phase II Phase II Phase II Phase I Phase I Phase I Phase I Phase I [NPS-1506 provides neuroprotecti on]

Lundbeck Neuropeptide Y receptor antagonist mGluR5 receptor antagonist Lundbeck Novartis

Phase I Phase I Phase I

JNJ-19567470 or TS-041 SSR 125543

CRF1 antagonist

CRF1 antagonist

Janssen (Johnson & Johnson), Taisho SanofiAventis SK Pharmaceuti cals GSK Targacept Targacept AstraZeneca Roche Organon Neurogen SanofiAventis

Depression, anxiety Depression, anxiety, hyperphagi a Anxiety

Phase I

Phase I

YKP3089

Undisclosed mechanism of action Mixed serotonin receptor agonist Nicotinic acetylcholine receptor (alpha4beta2) antagonist Nonselective Nicotinic acetylcholine receptor antagonist Enkephalinergic modulator FAAH (fatty acid amide hydrolase) inhibitor CRF1 antagonist CRF1 antagonist

Phase I

163090 TC-2216 TC-5214 AZD2327 R1647 URB597 -SSR 126374

Depression, anxiety Depression Depression Anxiety Depression, anxiety Depression Depression, anxiety Depression, anxiety, hyperphagi a

Phase I Phase I Phase I Phase I Phase I Phase II Pre-clinical Pre-clinical

SSR 411298

FAAH (fatty acid amide hydrolase) inhibitor CRF1 antagonist

SanofiAventis

CRF1 antagonist (backup) R1661 SAR 102279 YKP581

Depression, anxiety, hyperphagi a GSK/Neurocri Depression, ne anxiety Roche SanofiAventis SK Pharmaceuti cals (J & J) Anxiety Depression, anxiety Depression

Pre-clinical

Pre-clinical Pre-clinical Pre-clinical Pre-clinical

NK2 receptor antagonist Undisclosed mechanism of action

Treatments for Sleep Disorders
Drug Name Indiplon IR; Indiplon MR Eplivanserin, SR 46349 Pharmacologic Action GABA-A modulator (at BZ1 sites) 5-HT2A receptor antagonist Company Neurocrine Indication Sleep disorders Sleep disorders Developmen tal Phase FDA decision expected by December 12, 2007 Phase III Links [Neurocrin e's info]

SanofiAventis

Silenor (doxepin)

Doxepin is a potent Somaxon antagonist at histamine H1 and H2 receptors. It may weakly inhibit the reuptake of norepinephrine and serotonin. Doxepin is also an antagonist at alpha-1-adrenoceptors. The drug binds to both serotonin 5-HT2A and 5-HT2C receptors. In addition, it is an antagonist at all subtypes of muscarinic acetylcholine receptors (references provided elsewhere). VEC-162 Melatonin receptor agonist Vanda Pharmaceutic als ORG 50081 5-HT2 antagonist, H1 Organon antagonist, alpha-2adrenoceptor antagonist Volinanserin, M- 5-HT2A antagonist Sanofi100907 Aventis APD125 5-HT2A inverse agonist Arena Adipiplon, NG273 PD-6735 Pruvanserin, EMD 281014 GABA-A modulator Melatonin receptor agonist 5-HT2A antagonist Neurogen Phase 2 Discovery Eli Lilly

Sleep disorders

Phase III

[Somaxon' s info]

Sleep disorders, depression Sleep disorders, hot flashes Sleep disorders Sleep disorders Sleep disorders Sleep Disorders Sleep disorders

Phase III Phase III Phase III Phase III Phase III Phase II Phase II

[Vanda's info]

[M-100907 review]

Pimavanserin, ACP-103

Serotonin 5-HT2A receptor inverse agonist, dopamine D2/D3 receptor partial agonist, acetylcholine M1 receptor agonist Alpha2delta calcium channel blocker 5-HT2A and histamine H1 receptor antagonist Melatonin agonist, 5-HT2B/5HT2C antagonist Orexin antagonist Orexen OX1 and OX2 receptor antagonist Voltage-gated calcium channel alpha(2)delta subunit modulator 5-HT2A antagonist

Acadia

PD 200-390

Pfizer

Sleep Phase II disorders, Parkinson's disease psychosis, schizophreni a co-therapy Sleep Phase II disorders Phase II Phase II Phase II Phase II Phase II Pre-clinical

[June 07 Press Release]

[11/06 Pfizer Presentati on]

HY10275 TIK-301, LY156735 GW649868 Almorexant, ACT-078573 PD-200,390 AVE 8488

Eli Lilly

Depression, ADHD Tikvah Sleep Pharmaceutic disorders als GSK Sleep disorders Actelion Sleep disorders Pfizer Sleep disorders SanofiAventis Sleep disorders

[Actelion's Web Site]

Treatments for Psychosis/Bipolar Disorder
Drug Name Pharmacologic Action Company Indication Development al Phase Links

Invega (Paliperidone IM, ER) Bifeprunox (DU127090) Zomaril (Iloperidone) Corlux (AKA mifepristone or RU-486)

Full 5-HT2/partial D2 antagonist with high affinity for 5-HT7 receptors. Active metabolite of Risperdal Partial agonist at dopamine D2 and serotonin 5-HT1A receptors Selective DA/NE/5-HT antagonist

Johnson & Johnson Solvay, Wyeth Vanda Pharmaceutic als Corcept

Psychosis

Approved

Psychosis Psychosis Psychosis, depression Psychosis

Not approvable NDA Submitted Phase III, granted fasttrack status by the FDA Phase III [Corcept 's info] [Organo n 2003 press release] Drug profile

Glucocorticoid receptor type II (GRII) antagonist, progesterone receptor antagonist Asenapine (ORG 5-HT2 antagonist, D2 partial 5222) agonist Ocaperidone SLV 308 LIC477D (licarbazepine) Pimavanserin, ACP-103 D2/5-HT2 antagonist D2 partial agonist, 5-HT1A agonist Voltage-gated sodium channel inhibitor Serotonin 5-HT2A receptor inverse agonist, dopamine D2/D3 receptor partial agonist, acetylcholine M1 receptor agonist Glucocorticoid receptor type II (GRII) antagonist

Organon

Neuro3d, Janssen Solvay Novartis Acadia

Psychosis Psychosis, Parkinson's disease Psychosis Antipsychoti c-induced side effects, Parkinson's disease psychosis Depression, psychosis

Phase III Phase III Phase III Phase III

[June 07 Press Release]

ORG 34517/34850

Organon

Phase II

ORG 24448 ACP-104 RG2133 (triacetyluridine ) Lonasen (blonanserin) LY2140023 Mirapex (pramipexole) Lu-35-138 Lurasidone (SM 13496) Talnetant (SB223412) AVE 1625 P-101 ORG 25935 RG1068, secretin SLV 310,313 SSR 181507

AMPA modulator Metabolite of clozapine Prodrug of uridine

Organon/Cort ex Acadia Repligen

Psychosis Psychosis Bipolar disorder

Phase II Phase II Phase II [Replige n's info] [10/21/0 5 press release]

D2, 5-HT2A antagonist Prodrug for an mGluR2/3 agonist Dopamine D2, D3 receptor agonist D4/5-HT antagonist D2, 5-HT2A antagonist NK-3 antagonist

Dainippon Sumitomo Eli Lilly BoehringerIngelheim Lundbeck Merck, Dainippon Sumitomo GSK

Psychosis Psychosis Bipolar Disorder Psychosis Psychosis

Phase II Phase II Phase II Phase II Phase II Phase II

CB1 antagonist Alpha-2-adrenoceptor antagonist GLYT1 (glycine transporter) inhibitor Endogenous pancreatic hormone 5-HT2A antagonist D2/5-HT2 antagonist

Psychosis, IBS, overactive bladder Sanofi-Aventis Psychosis Potomac Schizophreni Pharma a Organon Psychosis Repligen Psychosis, autism, anxiety Solvay Psychosis Sanofi-Aventis Psychosis

Phase II Phase II Phase II Phase II Phase II Phase I

ABT-089 GW742457 GW773812 TC-1827

Nicotinic acetylcholine receptor agonist 5-HT6 antagonist D2, 5-HT antagonist Selective alpha4beta2 nicotinic acetylcholine receptor agonist

Abbott Laboratories GSK GSK Targacept

YKP 1538 SSR 125047 SSR 504734 JNJ-17305600 XY 2401 PNU 170413 RGH-188 PDE10A SSR 180711 SSR 103800 SSR 241586 Sigma receptor antagonist GLYT1 (Type 1 glycine transporter) inhibitor GLYT1 inhibitor Glycine site specific NMDA modulator D2, D3 antagonist PDE10A inhibitor alpha7 nicotinic acetylcholine receptor partial agonist GLYT1 (Type 1 glycine transporter) inhibitor NK3 antagonist

SK Pharmaceutic als Sanofi-Aventis Psychosis Sanofi-Aventis Psychosis Johnson & Johnson Xytis Pfizer Forrest Memory Pharm./ Roche Sanofi-Aventis Psychosis Psychosis Psychosis Psychosis Psychosis Psychosis

Psychosis, ADHD Psychosis, Alzheimer's disease Psychosis Cognitive impairment associated with schizophreni a Psychosis

Phase I Phase I Phase I Phase I

Phase I Phase I Phase I Phase I Phase I Phase I Phase I Preclinical Preclinical Preclinical Preclinical

Sanofi-Aventis Psychosis Sanofi-Aventis Psychosis

Treatments for Attention Deficit Hyperactivity Disorder (ADHD)
Drug Name Vyvanse Pharmacologic Action Amphetamine conjugated to a specific amino acid Company Shire Pharmaceutic als/ New River Pharmaceutic als Shire Pharmaceutic als Shire Pharmaceutic als Cortex Pharmaceutic als Indication ADHD Development al Phase Approved Links [New River compou nd info]

SPD-465 (longer Long-acting amphetamine acting Adderall product XR) Intuniv (SPD503, guanfacine) CX-717 Alpha-2A-adrenoceptor agonist AMPA receptor modulator

ADHD

ADHD

ADHD

Altropane ABT-089 ABT-894 PF-03654746 MEM3454

Highly selective dopamine transporter radioligand Nicotinic acetylcholine receptor agonist Nicotinic acetylcholine receptor agonist

Boston Life Sciences Abbott Laboratories Abbott Laboratories Pfizer Alpha-7 nicotinic acetylcholine Memory

ADHD ADHD, Psychosis ADHD ADHD ADHD

Approvable, awaiting final FDA approval Approvable, awaiting final FDA approval The FDA has rejected the request for the ADHD indication... Will not pursue Phase II Phase II Phase II Phase II Phase II [Memor

receptor partial agonist DOV-102,677 SON-216 (bifemelane) SPD-483 DA/NE/5-HT reuptake inhibitor (with preferential action on the dopamine transporter) ATS (Amphetamine Transdermal System)

Pharm./ Roche DOV Pharmaceutic als Sosei Shire Pharmaceutic als

y's drug profile] ADHD ADHD ADHD Phase I Phase I Preclinical

APPENDIX: Glossary
Phase I: Phase I includes the initial introduction of an investigational new drug into humans. Phase I studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. During Phase I, sufficient information about the drug's pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase II studies. The total number of subjects and patients included in Phase I studies varies with the drug, but is generally in the range of 20 to 80. Phase II: Phase II includes the controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug. Phase II studies are typically well controlled, closely monitored, and conducted in a relatively small number of patients, usually involving no more than several hundred subjects. Phase III: A phase III trial frequently compares a new treatment to a standard treatment or to no treatment, and treatment allocation may be randomly assigned and the data masked. These studies usually involve a large number of participants followed for longer periods of treatment exposure. Phase III studies are expanded controlled and uncontrolled trials. Phase III studies usually include from several hundred to several thousand subjects. NDA: New Drug Application. NDA refers to the data that the drug company submits to the FDA at the time of the drug's application filing.

Approvable:
Term giving to a drug's approval status by the FDA. Before the drug can be launched, the company has to fulfill ongoing clinical and manufacturing concerns brought up by the FDA.