DOCSLIB.ORG

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

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD This list was graciously provided by JR Becker ([email protected]). Some additions have been made by Shawn Thomas ([email protected]). Please send additions or corrections to [email protected] 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 Links tal Phase Pristiq (DVS- Metabolite of Effexor Wyeth Depression, Approvable 233 SR, (venlafaxine) anxiety (but further desvenlafaxine needed ) Phase III trials suggest a 2008 approval date) Gepirone ER 5-HT1A partial agonist Fabre- Depression, Not [Fabre- Kramer anxiety Approvable Kramer's Drug Profile] Saredutant (SR NK2 antagonist Sanofi- Depression, Phase III [Effects of SR 48968) Aventis anxiety 48968 on rodents] Valdoxan 5-HT2C antagonist, 5-HT2B Servier, Depression, EU: [Receptor (agomelatine, antagonist, melatonin M1/M2 Novartis anxiety, Resubmissio activity] [Oct AGO 178) receptor agonist sleep n planned in 2005 press disorders ’07. US: release] Phase III Amibegron, SR beta-3-adrenoceptor agonist Sanofi- Depression, A [SR 58611 is 58611 Aventis anxiety supplement a selective al NDA is beta-3- possible in adrenoceptor 2007 agonist] Vilazodone 5-HT1A partial agonist, Clinical Data Depression Phase III [January serotonin reuptake inhibitor Online, Inc. 2007 Press Release] Pexacerfont, CRF1 antagonist Bristol-Myers Depression, Phase III BMS-562086 Squibb anxiety Lu AA21004 bis-aryl-sulphanyl modulator Lundbeck Depression, Phase II anxiety Casopitant, NK1 antagonist GSK Depression, Phase II GW679769 anxiety, emesis PRX-00023 5-HT1A agonist, sigma Epix Depression Phase II [Compound receptor antagonist Profile] Miraxion, LAX- "Purified" Omega-3 [EPA] Amarin Huntington' Phase II 101 s Disease, Depression TIK-101 NMDA Antagonist Tikvah Anxiety Phase II Pharmaceuti cals TGWOOAD/AA 5-HT1A agonist, 5-HT2 Fabre- Anxiety Phase II [Fabre- antagonist Kramer Kramer's info] TGBA01AD Serotonin reuptake inhibitor, Fabre- Depression Phase II [Fabre- 5-HT2 agonist, 5-HT1A Kramer Kramer's agonist, and 5-HT1D agonist info] GW372475, Dopamine, serotonin, and GSK, Depression Phase II NS2359 norepinephrine, reuptake NeuroSearch inhibitor Nemifitide Pentapeptide analog of Tetragenex Depression Phase II [Innapharma' (INN 00835) melanocyte-inhibiting factor s info] (MIF-1) administered [Antidepressa intravenously (mechanism nt-like effects unknown) of a novel pentapeptide , nemifitide, in an animal model of depression] [MIF-1 may regulate ACTH secretion] ORG GR antagonist Organon Depression Phase II 34517/34850 Vestipitant, NK1 antagonist GSK Depression, Phase II GW597599 anxiety DOV 21, 947 Dopamine, serotonin, and DOV/Merck Depression, Phase II [Antidepressa norepinephrine, reuptake ADHD, RLS nt-like inhibitor actions of DOV 21,947] LY2216684 Norepinephrine reuptake Eli Lilly Depression, Phase II inhibitor ADHD YKP-10A, Phenylalanine derivative with Janssen Depression Phase II [First Phase II R228060 unknown mechanism (Johnson & Study] Johnson)/SK Pharmaceuti cals PD 332-334 Alpha2delta calcium channel Pfizer Anxiety Phase II [11/06 Pfizer blocker Presentation] Elzasonan, CP- 5-HT1B and 5-HT1D receptor Pfizer Depression, Phase II 448,187 antagonist anxiety Lu AA24530 Multiple targets Lundbeck Depression, Phase II anxiety SEP-225289 DA/NE/5-HT reuptake Sepracor Depression, Phase I inhibitor anxiety SSR149415 V1B antagonist Sanofi- Depression, Phase II [SSR149415 Aventis anxiety, review] hyperphagi a AZD6765 - AstraZeneca Depression, Phase II anxiety GW876008 CRF1 antagonist Neurocrine/G Depression, Phase II SK anxiety, IBS ONO-2333Ms CRF1 antagonist Ono Depression, Phase II Pharmaceuti anxiety cals R-tofisopam R-isomer of racemic Pharmos Anxiety, IBS Phase I tofisopam (a 2,3- benzodiazepine) GW823296 NK1 antagonist GSK Depression, Phase I (orvepitant) anxiety Tyrima Reversible monoamine CeNeRx Depression, Phase I oxidase A (MAO-A) inhibitor anxiety PRE703 MgluR agonist Prescient Anxiety Phase I Delucemine, NMDA antagonist NPS Depression, Phase I [NPS-1506 NPS 1506 stroke provides neuroprotecti on] Lu AA34893 Lundbeck Depression, Phase I anxiety Lu AA44608 Neuropeptide Y receptor Lundbeck Depression, Phase I antagonist anxiety AFQ056 mGluR5 receptor antagonist Novartis Anxiety Phase I JNJ-19567470 CRF1 antagonist Janssen Depression, Phase I or TS-041 (Johnson & anxiety Johnson), Taisho SSR 125543 CRF1 antagonist Sanofi- Depression, Phase I Aventis anxiety, hyperphagi a YKP3089 Undisclosed mechanism of SK Anxiety Phase I action Pharmaceuti cals 163090 Mixed serotonin receptor GSK Depression, Phase I agonist anxiety TC-2216 Nicotinic acetylcholine Targacept Depression Phase I receptor (alpha4beta2) antagonist TC-5214 Nonselective Nicotinic Targacept Depression Phase I acetylcholine receptor antagonist AZD2327 Enkephalinergic modulator AstraZeneca Anxiety Phase I R1647 Roche Depression, Phase I anxiety URB597 FAAH (fatty acid amide Organon Depression Phase II hydrolase) inhibitor -- CRF1 antagonist Neurogen Depression, Pre-clinical anxiety SSR 126374 CRF1 antagonist Sanofi- Depression, Pre-clinical Aventis anxiety, hyperphagi a SSR 411298 FAAH (fatty acid amide Sanofi- Depression, Pre-clinical hydrolase) inhibitor Aventis anxiety, hyperphagi a CRF1 CRF1 antagonist GSK/Neurocri Depression, Pre-clinical antagonist ne anxiety (backup) R1661 Roche Anxiety Pre-clinical SAR 102279 NK2 receptor antagonist Sanofi- Depression, Pre-clinical Aventis anxiety YKP581 Undisclosed mechanism of SK Depression Pre-clinical action Pharmaceuti cals (J & J) Treatments for Sleep Disorders Drug Name Pharmacologic Action Company Indication Developmen Links tal Phase Indiplon IR; GABA-A modulator (at BZ1 Neurocrine Sleep FDA decision [Neurocrin Indiplon MR sites) disorders expected by e's info] December 12, 2007 Eplivanserin, 5-HT2A receptor antagonist Sanofi- Sleep Phase III SR 46349 Aventis disorders Silenor Doxepin is a potent Somaxon Sleep Phase III [Somaxon' (doxepin) antagonist at histamine H1 disorders s info] 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 Sleep Phase III [Vanda's Pharmaceutic disorders, info] als depression ORG 50081 5-HT2 antagonist, H1 Organon Sleep Phase III antagonist, alpha-2- disorders, adrenoceptor antagonist hot flashes Volinanserin, M- 5-HT2A antagonist Sanofi- Sleep Phase III [M-100907 100907 Aventis disorders review] APD125 5-HT2A inverse agonist Arena Sleep Phase III disorders Adipiplon, NG2- GABA-A modulator Neurogen Sleep Phase III 73 disorders PD-6735 Melatonin receptor agonist Phase 2 Sleep Phase II Discovery Disorders Pruvanserin, 5-HT2A antagonist Eli Lilly Sleep Phase II EMD 281014 disorders Pimavanserin, Serotonin 5-HT2A receptor Acadia Sleep Phase II [June 07 ACP-103 inverse agonist, dopamine disorders, Press D2/D3 receptor partial Parkinson's Release] agonist, acetylcholine M1 disease receptor agonist psychosis, schizophreni a co-therapy PD 200-390 Alpha2delta calcium channel Pfizer Sleep Phase II [11/06 blocker disorders Pfizer Presentati on] HY10275 5-HT2A and histamine H1 Eli Lilly Depression, Phase II receptor antagonist ADHD TIK-301, Melatonin agonist, 5-HT2B/5- Tikvah Sleep Phase II LY156735 HT2C antagonist Pharmaceutic disorders als GW649868 Orexin antagonist GSK Sleep Phase II disorders Almorexant, Orexen OX1 and OX2 receptor Actelion Sleep Phase II [Actelion's ACT-078573 antagonist disorders Web Site] PD-200,390 Voltage-gated calcium Pfizer Sleep Phase II channel alpha(2)delta subunit disorders modulator AVE 8488 5-HT2A antagonist Sanofi- Sleep Pre-clinical Aventis disorders Treatments for Psychosis/Bipolar Disorder Drug Name Pharmacologic Action Company Indication Development Links al Phase Invega Full 5-HT2/partial D2 Johnson & Psychosis Approved (Paliperidone antagonist with high affinity Johnson IM, ER) for 5-HT7 receptors. Active metabolite of Risperdal Bifeprunox (DU- Partial agonist at dopamine Solvay, Psychosis Not 127090) D2 and serotonin 5-HT1A Wyeth approvable receptors Zomaril Selective DA/NE/5-HT Vanda Psychosis NDA (Iloperidone) antagonist Pharmaceutic Submitted als Corlux (AKA Glucocorticoid receptor type II Corcept Psychosis, Phase III, [Corcept mifepristone or (GRII) antagonist, depression granted fast- 's info] RU-486) progesterone receptor track status antagonist by the FDA Asenapine (ORG 5-HT2 antagonist, D2 partial Organon Psychosis Phase III [Organo 5222) agonist n 2003 press release] Ocaperidone D2/5-HT2 antagonist Neuro3d, Psychosis Phase III Drug Janssen profile SLV 308 D2 partial agonist, 5-HT1A Solvay Psychosis, Phase III agonist Parkinson's disease LIC477D Voltage-gated sodium channel Novartis Psychosis
Load more

Recommended publications
  • Evidence-Based Guidelines for Treating Depressive Disorders with Antidepressants
    JOP0010.1177/0269881115581093Journal of PsychopharmacologyCleare et al. 581093research-article2015 BAP Guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association Journal of Psychopharmacology 2015, Vol. 29(5) 459 –525 for Psychopharmacology guidelines © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881115581093 jop.sagepub.com Anthony Cleare1, CM Pariante2 and AH Young3 With expert co-authors (in alphabetical order): IM Anderson4, D Christmas5, PJ Cowen6, C Dickens7, IN Ferrier8, J Geddes9, S Gilbody10, PM Haddad11, C Katona12, G Lewis12, A Malizia13, RH McAllister-Williams14, P Ramchandani15, J Scott16, D Taylor17, R Uher18 and the members of the Consensus Meeting19 Endorsed by the British Association for Psychopharmacology Abstract A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations
    [Show full text]
  • Compositions for Treating Centrally Mediated
    (19) TZZ Z_T (11) EP 2 722 045 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/4178 (2006.01) A61K 31/473 (2006.01) 06.07.2016 Bulletin 2016/27 A61K 31/496 (2006.01) A61K 31/573 (2006.01) A61K 45/06 (2006.01) A61K 9/00 (2006.01) (2006.01) (2006.01) (21) Application number: 14151683.1 A61K 9/20 A61K 9/48 A61P 1/08 (2006.01) (22) Date of filing: 18.11.2010 (54) Compositions for treating centrally mediated nausea and vomiting Zusammensetzungen zur Behandlung von zentral vermitteltem Unwohlsein und Erbrechen Compositions pour traiter les nausées et vomissements à médiation centrale (84) Designated Contracting States: (56) References cited: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB WO-A1-2008/049552 WO-A2-2007/096763 GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR • REDDY G KESAVA ET AL: "Novel neurokinin-1 antagonists as antiemetics for the treatment of (30) Priority: 18.11.2009 US 262470 P chemotherapy-induced emesis.", SUPPORTIVE 14.09.2010 US 382709 P CANCER THERAPY 1 APR 2006 LNKD- PUBMED:18632487, vol. 3, no. 3, 1 April 2006 (43) Date of publication of application: (2006-04-01), pages140-142, XP002626039, ISSN: 23.04.2014 Bulletin 2014/17 1543-2912 • DIEMUNSCH P ET AL: "Neurokinin-1 receptor (62) Document number(s) of the earlier application(s) in antagonists in the prevention of postoperative accordance with Art.
    [Show full text]
  • ( 12 ) United States Patent
    US009974742B2 (12 ) United States Patent (10 ) Patent No. : US 9 , 974 , 742 B2 Ottoboni et al. (45 ) Date of Patent: * May 22, 2018 ( 54 ) EMULSION FORMULATIONS OF AN NK - 1 2013 /0236501 A1 * 9 /2013 Booth . .. .. .. A61K 9 /0019 424 / 400 RECEPTOR ANTAGONIST AND USES 2013 /0317016 AL 11 /2013 Hingorani et al. THEREOF 2016 / 0024092 Al 1 / 2016 Wan et al. 2016 / 0082013 Al 3 / 2016 Ottoboni et al . @(71 ) Applicant : Heron Therapeutics , Inc. , Redwood 2016 /0206622 A1 3 / 2016 Ottoboni et al . City , CA (US ) 2017 / 0112847 AL 4 /2017 Ottoboni et al. @(72 ) Inventors : Thomas B . Ottoboni, Belmont, CA (US ) ; Han Han , Mountain View , CA FOREIGN PATENT DOCUMENTS (US ) CN 102379 * 3 / 2012 CN 102379845 A 3 / 2012 @(73 ) Assignee : Heron Therapeutics, Inc. , San Diego , WO WO 2005 /016308 AL 2 / 2005 WO WO 2009 / 124756 AL 10 / 2009 CA (US ) WO WO 2011 / 158053 AL 12 / 2011 WO WO 2013 / 177501 A2 11 / 2013 @( * ) Notice : Subject to any disclaimer , the term of this WO WO 2014 /0209962 AL 12 /2014 patent is extended or adjusted under 35 WO WO 2014 /005606 AL 3 / 2016 U . S . C . 154 ( b ) by 0 days . days . WO WO 2016 /044784 Al 3 / 2016 This patent is subject to a terminal dis claimer . OTHER PUBLICATIONS (21 ) Appl. No. : 15 /012 , 532 Cassileth et al. in Arch . Intern Med . 1983 ; 143 ( 7 ) : 1347 - 1349 ( Abstract ) . * Dexamethasone Hydrogen Phosphate at web .archive . org/ web / ( 22 ) Filed : Feb . 1 , 2016 20141224130045 /http :/ /www . drugs . com / pro / dexamethasone -so dium -phosphate .html ( retrieved on the internet Mar.
    [Show full text]
  • 1 Advances in Therapeutic Peptides Targeting G Protein-Coupled
    Advances in therapeutic peptides targeting G protein-coupled receptors Anthony P. Davenport1Ϯ Conor C.G. Scully2Ϯ, Chris de Graaf2, Alastair J. H. Brown2 and Janet J. Maguire1 1Experimental Medicine and Immunotherapeutics, Addenbrooke’s Hospital, University of Cambridge, CB2 0QQ, UK 2Sosei Heptares, Granta Park, Cambridge, CB21 6DG, UK. Ϯ Contributed equally Correspondence to Anthony P. Davenport email: [email protected] Abstract Dysregulation of peptide-activated pathways causes a range of diseases, fostering the discovery and clinical development of peptide drugs. Many endogenous peptides activate G protein-coupled receptors (GPCRs) — nearly fifty GPCR peptide drugs have been approved to date, most of them for metabolic disease or oncology, and more than 10 potentially first- in-class peptide therapeutics are in the pipeline. The majority of existing peptide therapeutics are agonists, which reflects the currently dominant strategy of modifying the endogenous peptide sequence of ligands for peptide-binding GPCRs. Increasingly, novel strategies are being employed to develop both agonists and antagonists, and both to introduce chemical novelty and improve drug-like properties. Pharmacodynamic improvements are evolving to bias ligands to activate specific downstream signalling pathways in order to optimise efficacy and reduce side effects. In pharmacokinetics, modifications that increase plasma-half life have been revolutionary. Here, we discuss the current status of peptide drugs targeting GPCRs, with a focus on evolving strategies to improve pharmacokinetic and pharmacodynamic properties. Introduction G protein-coupled receptors (GPCRs) mediate a wide range of signalling processes and are targeted by one third of drugs in clinical use1. Although most GPCR-targeting therapeutics are small molecules2, the endogenous ligands for many GPCRs are peptides (comprising 50 or fewer amino acids), which suggests that this class of molecule could be therapeutically useful.
    [Show full text]
  • Antidepressant-Like Effects of the Vasopressin V1b Receptor Antagonist SSR149415 in the Flinders Sensitive Line Rat
    Pharmacology, Biochemistry and Behavior 82 (2005) 223 – 227 www.elsevier.com/locate/pharmbiochembeh Antidepressant-like effects of the vasopressin V1b receptor antagonist SSR149415 in the Flinders Sensitive Line rat David H. Overstreet a,*, Guy Griebel b a Department of Psychiatry and Bowles Center for Alcohol Studies, CB 7178, 429 Taylor Bldg., University of North Carolina, Chapel Hill, NC 27599-7178, USA b Sanofi-Aventis, Avenue P.V. Couturier, 92220 Bagneux, France Received 13 April 2005; received in revised form 18 July 2005; accepted 18 July 2005 Abstract There is an increased interest in the potential of vasopressin receptor antagonists as antidepressants because of the involvement of vasopressin in stress-related behavioral changes. The present study sought to provide confirmatory evidence for the antidepressant-like effects of the selective vasopressin V1b receptor antagonist SSR149415, which had been previously demonstrated in a variety of animal models. The Flinders Sensitive Line (FSL) rat, a selectively bred animal model of depression, was chronically treated for 14 days with SSR149415 (1, 10, and 30 mg/kg), vehicle, or desipramine (5 mg/kg) as a positive control. Approximately 22–24 h after the last treatment, the rats were exposed to a single 5-min session in a cylinder containing 25 -C water and immobility was recorded. A control group of Flinders Resistant Line (FRL) rats was included as a reference group as well as one treated with 10 mg/kg SSR149415. Vehicle-treated FSL rats exhibited much more immobility than the FRL rats, and desipramine-treated FSL rats had much lower scores, as expected. Treatment with SSR149415 reduced immobility in the FSL rats at all doses, but only the higher doses reduced it such that they were no longer different from the FRL rats.
    [Show full text]
  • Datasheet Inhibitors / Agonists / Screening Libraries a DRUG SCREENING EXPERT
    Datasheet Inhibitors / Agonists / Screening Libraries A DRUG SCREENING EXPERT Product Name : Nemifitide diTFA Catalog Number : TP1127 CAS Number : 204992-09-6 Molecular Formula : C37H45F7N10O10 Molecular Weight : 922.80 Description: Nemifitide (diTFA) is is a synthetic pentapeptide antidepressant with a potential for rapid onset of action. Nemifitide (diTFA) is a peptide analog of melanocyte-inhibiting factor (MIF). Storage: 2 years -80°C in solvent; 3 years -20°C powder; In vitro Activity In-vitro studies indicate that both nemifitide and its active metabolite (M1) bind at micromolar concentrations to several receptors including the 5-HT2A, 5-HT2C, melanocortin MC4, MC5 and bombesin[3]. In vivo Activity Nemifitide (0.3 mg/kg; IP; daily; for 14 days) significantly increases swimming in the FSL rats after just 5 days of treatment and has long-lasting effect[2]. Nemifitide (0.0125-15.0 mg/kg) significantly increases swimming in the FSL rats at both low (0.025- 0.3 mg/kg) and high (3.0-15.0 mg/kg) doses but not at intermediate (0.4-2.4 mg/kg) doses[2]. Reference 1. Kelly JP, et al. The effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in depressed patients. J Affect Disord. 1999 Oct;55(2-3):231-5. 2. Overstreet DH, et al. Antidepressant-like effects of a novel pentapeptide, nemifitide, in an animal model of depression. Psychopharmacology (Berl). 2004 Sep;175(3):303-9. 3. Montgomery SA, et al. Efficacy and safety of 30 mg/d and 45 mg/d nemifitide compared to placebo in major depressivedisorder.
    [Show full text]
  • I Regulations
    23.2.2007 EN Official Journal of the European Union L 56/1 I (Acts adopted under the EC Treaty/Euratom Treaty whose publication is obligatory) REGULATIONS COUNCIL REGULATION (EC) No 129/2007 of 12 February 2007 providing for duty-free treatment for specified pharmaceutical active ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation and specified products used for the manufacture of finished pharmaceuticals and amending Annex I to Regulation (EEC) No 2658/87 THE COUNCIL OF THE EUROPEAN UNION, (4) In the course of three such reviews it was concluded that a certain number of additional INNs and intermediates used for production and manufacture of finished pharmaceu- ticals should be granted duty-free treatment, that certain of Having regard to the Treaty establishing the European Commu- these intermediates should be transferred to the list of INNs, nity, and in particular Article 133 thereof, and that the list of specified prefixes and suffixes for salts, esters or hydrates of INNs should be expanded. Having regard to the proposal from the Commission, (5) Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Common Customs Tariff (1) established the Combined Nomenclature Whereas: (CN) and set out the conventional duty rates of the Common Customs Tariff. (1) In the course of the Uruguay Round negotiations, the Community and a number of countries agreed that duty- (6) Regulation (EEC) No 2658/87 should therefore be amended free treatment should be granted to pharmaceutical accordingly, products falling within the Harmonised System (HS) Chapter 30 and HS headings 2936, 2937, 2939 and 2941 as well as to designated pharmaceutical active HAS ADOPTED THIS REGULATION: ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation, specified salts, esters or hydrates of such INNs, and designated inter- Article 1 mediates used for the production and manufacture of finished products.
    [Show full text]
  • Neurokinin Receptor NK Receptor
    Neurokinin Receptor NK receptor There are three main classes of neurokinin receptors: NK1R (the substance P preferring receptor), NK2R, and NK3R. These tachykinin receptors belong to the class I (rhodopsin-like) G-protein coupled receptor (GPCR) family. The various tachykinins have different binding affinities to the neurokinin receptors: NK1R, NK2R, and NK3R. These neurokinin receptors are in the superfamily of transmembrane G-protein coupled receptors (GPCR) and contain seven transmembrane loops. Neurokinin-1 receptor interacts with the Gαq-protein and induces activation of phospholipase C followed by production of inositol triphosphate (IP3) leading to elevation of intracellular calcium as a second messenger. Further, cyclic AMP (cAMP) is stimulated by NK1R coupled to the Gαs-protein. The neurokinin receptors are expressed on many cell types and tissues. www.MedChemExpress.com 1 Neurokinin Receptor Antagonists, Agonists, Inhibitors, Modulators & Activators Aprepitant Befetupitant (MK-0869; MK-869; L-754030) Cat. No.: HY-10052 (Ro67-5930) Cat. No.: HY-19670 Aprepitant (MK-0869) is a selective and Befetupitant is a high-affinity, nonpeptide, high-affinity neurokinin 1 receptor antagonist competitive tachykinin 1 receptor (NK1R) with a Kd of 86 pM. antagonist. Purity: 99.67% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mg Size: 1 mg, 5 mg Biotin-Substance P Casopitant mesylate Cat. No.: HY-P2546 (GW679769B) Cat. No.: HY-14405A Biotin-Substance P is the biotin tagged Substance Casopitant mesylate (GW679769B) is a potent, P. Substance P (Neurokinin P) is a neuropeptide, selective, brain permeable and orally active acting as a neurotransmitter and as a neurokinin 1 (NK1) receptor antagonist.
    [Show full text]
  • United States Patent (10) Patent No.: US 7,368,477 B2 Gross Et Al
    USOO7368477B2 (12) United States Patent (10) Patent No.: US 7,368,477 B2 Gross et al. (45) Date of Patent: May 6, 2008 (54) BENZOFURANYLALKANAMINE 6,419,958 B2 7/2002 Sherman et al. DERVATIVES AND USES THEREOF 6,444,708 B2 9/2002 Rudolph et al. 6,765,008 B1 7, 2004 Chen (75) Inventors: Jonathan Laird Gross, Cranbury, NJ 6,967.201 B1 1 1/2005 Briner et al. (US); Gary Paul Stack, Ambler, PA 7,045,545 B1 5, 2006 Briner et al. (US); Dahui Zhou, East Brunswick, NJ 2002/0183395 Al 12/2002 Argentieri et al. (US); Hong Gao, Belle Mead, NJ (US) 2004.0029949 A1 2/2004 Argentieri et al. 2004/0235856 Al 11/2004 McMurray et al. (73) Assignee: Wyeth, Madison, NJ (US) 2005, 0124692 A1 6/2005 Gross et al. 2005.01434.52 A1 6/2005 Gross et al. (*) Notice: Subject to any disclaimer, the term of this 2005/0261347 A1 11/2005 Gross et al. patent is extended or adjusted under 35 2006,008.9405 A1 4, 2006 Zhou U.S.C. 154(b) by 99 days. 2006/0111438 A1 5/2006 Gontcharov et al. 2006/0241172 A1 10, 2006 Zhou et al. (21) Appl. No.: 11/408,319 2006/0241176 A1 10, 2006 Stack et al. 2006/0246551 A1 11/2006 Stack et al. (22) Filed: Apr. 21, 2006 2006/0247276 A1 11/2006 Gross et al. 2006/0252825 A1 11/2006 Tadayon et al. (65) Prior Publication Data 2006/0258639 A1 11/2006 Logue et al. 2006/0258711 A1 11/2006 Rosenzweig-Lipson US 2006/O24727.6 A1 Nov.
    [Show full text]
  • Emerging Targets for Antidepressant Therapies Jeffrey J Rakofsky1, Paul E Holtzheimer2 and Charles B Nemeroff2
    Available online at www.sciencedirect.com Emerging targets for antidepressant therapies Jeffrey J Rakofsky1, Paul E Holtzheimer2 and Charles B Nemeroff2 Despite adequate antidepressant monotherapy, the majority of 70% of depressed patients have residual symptoms [3], depressed patients do not achieve remission. Even optimal and and, even with more aggressive therapies, 20% or more aggressive therapy leads to a substantial number of patients may show only a limited response [4]. Rather than being who show minimal and often only transient improvement. In the exception, recurrent episodes are the rule, and there order to address this substantial problem of treatment-resistant are few evidence-based approaches to help clinicians depression, a number of novel targets for antidepressant maintain a patient’s antidepressant response. Persistent therapy have emerged as a consequence of major advances in depression is associated with an increase in substance and the neurobiology of depression. Three major approaches to alcohol abuse, an increased risk for suicide and for car- uncover novel therapeutic interventions are: first, optimizing the diovascular disease. Thus, improved treatments for modulation of monoaminergic neurotransmission; second, depression are urgently needed. developing medications that act upon neurotransmitter systems other than monoaminergic circuits; and third, using Various forms of psychotherapy, pharmacotherapy, and focal brain stimulation to directly modulate neuronal activity. electroconvulsive therapy (ECT) are currently the most We review the most recent data on novel therapeutic commonly used antidepressant treatments. Serendipitous compounds and their antidepressant potential. These include discoveries and/or a limited understanding of the triple monoamine reuptake inhibitors, atypical antipsychotic neurobiology of depression which largely focused on the augmentation, and dopamine receptor agonists.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]