Learn and talk about L-733,060, Antidepressants, Anxiolytics, Ethers, NK1 receptor antagonists

L-733,060

Systematic (IUPAC) name
(2S,3S)-3-{[3,5-bis(trifluoromethyl)benzyl]oxy}-2-phenylpiperidine
Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
CAS number	148700-85-0^Y
ATC code	?
PubChem	CID 132846
ChEMBL	CHEMBL27006
Chemical data
Formula	C₂₀H₁₉F₆N O
Mol. mass	403.361 g/mol
SMILES FC(F)(F)c(c2)cc(C(F)(F)F)cc2COC1CCCNC1c3ccccc3
Y (what is this?) (verify)

L-733,060 is a drug developed by Merck, Sharpe & Dohme which acts as an orally active, non-peptide, selective antagonist for the NK₁ receptor, binding with a Ki of 0.08nM.^[1] Only one enantiomer is active which has made it the subject of several asymmetric synthesis efforts.^[2]^[3]^[4]

L-733,060 has antidepressant^[5]^[6] and anxiolytic effects in animal studies,^[7] and reduces both the dopamine release and neurotoxicity produced by methamphetamine and cocaine.^[8]^[9]^[10]^[11]^[12] It shows antiinflammatory and anti-hepatotoxic effects in animals,^[13]^[14] and counteracts the development of hyperalgesia following nerve injury.^[15]^[16] It also has anticancer effects in a variety of in vitro models.^[17]^[18]^[19]

References [edit]

^ Seabrook, GR, Shepheard, SL, Williamson, DJ, Tyrer, P, Rigby, M, Cascieri, MA, Harrison, T, Hargreaves, RJ et al. (1996). "L-733,060, a novel tachykinin NK1 receptor antagonist; effects in Ca2+i mobilisation, cardiovascular and dural extravasation assays". European Journal of Pharmacology 317 (1): 129–35. doi:10.1016/S0014-2999(96)00706-6. PMID 8982729. |displayauthors= suggested (help)
^ Liu, LX, Ruan, YP, Guo, ZQ, Huang, PQ (2004). "A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones: application to the asymmetric syntheses of neurokinin substance P receptor antagonist (-)-L-733,061 and (-)-deoxocassine". The Journal of Organic Chemistry 69 (18): 6001–9. doi:10.1021/jo049166z. PMID 15373484.
^ Tsai, MR, Chen, BF, Cheng, CC, Chang, NC (2005). "A novel and highly regioselective approach to 5-methoxy-6-substituted-3-sulfonyl-delta-enlactams from 5-methoxy-3-sulfonyl glutarimide: synthesis of cis-2-substituted-3-piperidinols". The Journal of Organic Chemistry 70 (5): 1780–5. doi:10.1021/jo048073e. PMID 15730301.
^ Liu, RH, Fang, K, Wang, B, Xu, MH, Lin, GQ (2008). "Concise asymmetric synthesis of (+)-CP-99,994 and (+)-L-733,060 via efficient construction of homochiral syn-1,2-diamines and syn-1,2-amino alcohols". The Journal of Organic Chemistry 73 (8): 3307–10. doi:10.1021/jo8002979. PMID 18331063.
^ Varty, GB, Cohen-Williams, ME, Hunter, JC (2003). "The antidepressant-like effects of neurokinin NK1 receptor antagonists in a gerbil tail suspension test". Behavioural Pharmacology 14 (1): 87–95. doi:10.1097/01.fbp.0000055962.09493.e9. PMID 12576885.
^ Wallace-Boone, TL, Newton, AE, Wright, RN, Lodge, NJ, McElroy, JF (2008). "Behavioral and pharmacological validation of the gerbil forced-swim test: effects of neurokinin-1 receptor antagonists". Neuropsychopharmacology 33 (8): 1919–28. doi:10.1038/sj.npp.1301586. PMID 17912250.
^ Varty, GB, Cohen-Williams, ME, Morgan, CA, Pylak, U, Duffy, RA, Lachowicz, JE, Carey, GJ, Coffin, VL (2002). "The gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin NK1 receptor antagonists". Neuropsychopharmacology 27 (3): 371–9. doi:10.1016/S0893-133X(02)00313-5. PMID 12225694.
^ Kraft, M, Noailles, P, Angulo, JA (2001). "Substance P modulates cocaine-evoked dopamine overflow in the striatum of the rat brain". Annals of the New York Academy of Sciences 937: 121–31. PMID 11458533.
^ Yu, J, Allison, S, Ibrahim, D, Cadet, JL, Angulo, JA (2002). "Ontogeny of neurokinin-1 receptor mediation of methamphetamine neurotoxicity in the striatum of the mouse brain". Annals of the New York Academy of Sciences 965: 247–53. PMID 12105100.
^ Noailles, PA, Angulo, JA (2002). "Neurokinin receptors modulate the neurochemical actions of cocaine". Annals of the New York Academy of Sciences 965: 267–73. PMID 12105102.
^ Yu, J, Cadet, JL, Angulo, JA (2002). "Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain". Journal of Neurochemistry 83 (3): 613–22. doi:10.1046/j.1471-4159.2002.01155.x. PMID 12390523.
^ Loonam, TM, Noailles, PA, Yu, J, Zhu, JP, Angulo, JA (2003). "Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum". Life Sciences 73 (6): 727–39. doi:10.1016/S0024-3205(03)00393-X. PMID 12801594.
^ Bang, R, Sass, G, Kiemer, AK, Vollmar, AM, Neuhuber, WL, Tiegs, G (2003). "Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury". The Journal of Pharmacology and Experimental Therapeutics 305 (1): 31–9. doi:10.1124/jpet.102.043539. PMID 12649350.
^ Bang, R, Biburger, M, Neuhuber, WL, Tiegs, G (2004). "Neurokinin-1 receptor antagonists protect mice from CD95- and tumor necrosis factor-alpha-mediated apoptotic liver damage". The Journal of Pharmacology and Experimental Therapeutics 308 (3): 1174–80. doi:10.1124/jpet.103.059329. PMID 14617692.
^ Jang, JH, Nam, TS, Paik, KS, Leem, JW (2004). "Involvement of peripherally released substance P and calcitonin gene-related peptide in mediating mechanical hyperalgesia in a traumatic neuropathy model of the rat". Neuroscience letters 360 (3): 129–32. doi:10.1016/j.neulet.2004.02.043. PMID 15082150.
^ Rittner, HL, Lux, C, Labuz, D, Mousa, SA, Schäfer, M, Stein, C, Brack, A (2007). "Neurokinin-1 receptor antagonists inhibit the recruitment of opioid-containing leukocytes and impair peripheral antinociception". Anesthesiology 107 (6): 1009–17. doi:10.1097/01.anes.0000291454.90754.de. PMID 18043070.
^ Muñoz, M, Rosso, M, Coveñas, R, Montero, I, González-Moles, MA, Robles, MJ (2007). "Neurokinin-1 receptors located in human retinoblastoma cell lines: antitumor action of its antagonist, L-732,138". Investigative Ophthalmology & Visual Science 48 (6): 2775–81. doi:10.1167/iovs.05-1591. PMID 17525212.
^ Muñoz, M, Rosso, M, Aguilar, FJ, González-Moles, MA, Redondo, M, Esteban, F (2008). "NK-1 receptor antagonists induce apoptosis and counteract substance P-related mitogenesis in human laryngeal cancer cell line HEp-2". Investigational new drugs 26 (2): 111–8. doi:10.1007/s10637-007-9087-y. PMID 17906845.
^ Rosso, M, Robles-Frías, MJ, Coveñas, R, Salinas-Martín, MV, Muñoz, M (2008). "The NK-1 receptor is expressed in human primary gastric and colon adenocarcinomas and is involved in the antitumor action of L-733,060 and the mitogenic action of substance P on human gastrointestinal cancer cell lines". Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 (4): 245–54. doi:10.1159/000152942. PMID 18781096.

Antiemetics (A04)

5-HT₃ Antagonists

CB₁ Agonists (Cannabinoids)

D₂/D₃ Antagonists

H₁ Antagonists (Antihistamines)

mACh Antagonists (Anticholinergics)

NK₁ Antagonists

Others

M: DIG

anat (t, g, p)/phys/devp/enzy

noco/cong/tumr, sysi/epon

proc, drug (A2A/2B/3/4/5/6/7/14/16), blte

Antidepressants (N06A)

Specific reuptake inhibitors (RIs), enhancers (REs), and releasing agents (RAs)

Selective serotonin reuptake inhibitors (SSRIs)	Alaproclate Citalopram Escitalopram Femoxetine Fluoxetine^# Fluvoxamine Indalpine Ifoxetine Litoxetine Lubazodone Omiloxetine Panuramine Paroxetine Pirandamine Seproxetine Sertraline^# Zimelidine^‡

Serotonin–norepinephrine reuptake inhibitors (SNRIs)	Clovoxamine Desvenlafaxine Duloxetine Levomilnacipran Eclanamine Milnacipran Sibutramine Venlafaxine

Serotonin–norepinephrine–dopamine reuptake inhibitors (SNDRIs)	Amitifadine Bicifadine Brasofensine BTS-74,398 Cocaine Diclofensine DOV-21,947 DOV-102,677 DOV-216,303 EXP-561 Fezolamine JNJ-7925476 NS-2359 PRC200-SS Pridefine SEP-225,289 SEP-227,162 Tesofensine

Norepinephrine reuptake inhibitors (NRIs)	Amedalin Atomoxetine/Tomoxetine Binedaline Ciclazindol Daledalin Edivoxetine Esreboxetine Lortalamine Mazindol Nisoxetine Reboxetine Talopram Talsupram Tandamine Viloxazine

Dopamine reuptake inhibitors (DRIs)	Medifoxamine Vanoxerine

Norepinephrine-dopamine reuptake inhibitors (NDRIs)	Amineptine Bupropion/Amfebutamone^# Cilobamine Manifaxine Methylphenidate Nomifensine Radafaxine Tametraline

Norepinephrine-dopamine releasing agents (NDRAs)	Amphetamine Befuraline Lisdexamfetamine Methamphetamine Phenethylamine Piberaline Tranylcypromine

Serotonin-norepinephrine-dopamine releasing agents (SNDRAs)	4-Methyl-αMT αET/Etryptamine αMT/Metryptamine

Selective serotonin reuptake enhancers (SSREs)	Tianeptine

Others	Indeloxazine Teniloxazine Tramadol Viqualine

Receptor antagonists and/or reuptake inhibitors

Serotonin antagonists and reuptake inhibitors (SARIs)	Etoperidone Nefazodone Trazodone

Noradrenergic and specific serotonergic antidepressants (NaSSAs)	Aptazapine Esmirtazapine Mianserin Mirtazapine Setiptiline/Teciptiline

Norepinephrine-dopamine disinhibitors (NDDIs)	Agomelatine

Serotonin modulators and stimulators (SMSs)	Vortioxetine

Others	Tedatioxetine Vilazodone

Heterocyclic antidepressants (bi-, tri-, and tetracyclics)

Bicyclics	Tiazesim Tofenacin

Tricyclics	Amezepine Amineptine Amitriptyline^# Amitriptylinoxide Azepindole Butriptyline Cianopramine Clomipramine Cotriptyline Cyanodothiepin Demexiptiline Depramine/Balipramine Desipramine Dibenzepin Dimetacrine Dosulepin/Dothiepin Doxepin Enprazepine Fluotracen Hepzidine Homopipramol Imipramine Imipraminoxide Intriptyline Iprindole Ketipramine Litracen Lofepramine Losindole Mariptiline Melitracen Metapramine Mezepine Naranol Nitroxazepine Nortriptyline Noxiptiline Octriptyline Opipramol Pipofezine Propizepine Protriptyline Quinupramine Tampramine Tianeptine Tienopramine Trimipramine

Tetracyclics	Amoxapine Aptazapine Azipramine Ciclazindol Ciclopramine Esmirtazapine Maprotiline Mazindol Mianserin Mirtazapine Oxaprotiline Setiptiline/Teciptiline

Monoamine oxidase inhibitors (MAOIs)

Nonselective	Irreversible: Benmoxin Carbenzide Cimemoxin Domoxin Echinopsidine Iproclozide Iproniazid Isocarboxazid Mebanazine Metfendrazine Nialamide Octamoxin Phenelzine Pheniprazine Phenoxypropazine Pivalylbenzhydrazine Safrazine Tranylcypromine Reversible: Caroxazone Paraxazone Quercetin

MAO_A-Selective	Irreversible: Clorgiline Reversible: Amiflamine Bazinaprine Befloxatone Berberine Brofaromine Cimoxatone Esuprone Eprobemide Harmala Alkaloids (Harmine Harmaline Tetrahydroharmine Harman Norharman, etc) Methylene Blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone Tyrima

MAO_B-Selective	Irreversible: Ladostigil Mofegiline Pargyline Rasagiline Selegiline Reversible: Lazabemide Milacemide

Azapirones and other 5-HT_1A receptor agonists

Alnespirone Aripiprazole Befiradol Buspirone Eptapirone Flesinoxan Flibanserin Gepirone Ipsapirone Oxaflozane Tandospirone Vilazodone Zalospirone

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)

Anxiolytics (N05B)

GABA_A
PAMs

non-N05B	Alcohols (2M2B, Ethanol (beverage), Ethchlorvynol, Methylpentynol) Chlormezanone Inhalants Etifoxine Kavalactones (Kava) Skullcap Valerenic acid (Valerian)

Benzodiazepine	Adinazolam Alprazolam Bretazenil Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam^# Ethyl Loflazepate Etizolam Fludiazepam Halazepam Imidazenil Ketazolam Lorazepam^# Medazepam Nordazepam Oxazepam Pinazepam Prazepam

Carbamates	Emylcamate Mebutamate Meprobamate (Carisoprodol, Tybamate) Phenprobamate Procymate

Nonbenzodiazepines	Abecarnil Adipiplon Alpidem CGS-8216 CGS-9896 CGS-13767 CGS-20625 Divaplon ELB-139 Fasiplon GBLD-345 Gedocarnil L-838,417 NS-2664 NS-2710 Ocinaplon Pagoclone Panadiplon Pipequaline RWJ-51204 SB-205,384 SL-651,498 Taniplon TP-003 TP-13 TPA-023 Y-23684 ZK-93423

Pyrazolopyridines	Cartazolate Etazolate ICI-190,622 Tracazolate

mGluR₂_/₃ Agonists

Eglumegad

mGluR5 NAMs

Fenobam

TSPO agonists

σ₁ agonists

Others

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)

Neuropeptidergics

Cholecystokinin

CCK_A	Agonists: Cholecystokinin CCK-4 Antagonists: Asperlicin Proglumide Lorglumide Devazepide Dexloxiglumide

CCK_B	Agonists: Cholecystokinin CCK-4 Gastrin Antagonists: Proglumide CI-988

CRH

CRF₁	Agonists: Corticotropin releasing hormone Antagonists: Antalarmin CP-154,526 Pexacerfont

CRF₂	Agonists: Corticotropin releasing hormone

Galanin

GAL₁	Agonists: Galanin Galanin-like peptide Galmic Galnon

GAL₂	Agonists: Galanin Galanin-like peptide Galmic Galnon

GAL₃	Agonists: Galanin Galmic Galnon

Ghrelin

GnRH

MCH

MCH₁	Agonists: Melanin concentrating hormone Antagonists: ATC-0175 GW-803,430 NGD-4715 SNAP-7941 SNAP-94847

MCH₂	Agonists: Melanin concentrating hormone

Melanocortin

MC₁	Agonists: alpha-MSH Afamelanotide BMS-470,539 Bremelanotide Melanotan II Antagonists: Agouti signalling peptide

MC₂	Agonists: ACTH Cosyntropin Tetracosactide

MC₃	Agonists: alpha-MSH Bremelanotide Melanotan II

MC₄	Agonists: alpha-MSH Bremelanotide Melanotan II PF-00446687 THIQ Antagonists: Agouti-related peptide

MC₅	Agonists: alpha-MSH Melanotan II

Neuropeptide S

Agonists: Neuropeptide S
Antagonists: SHA-68

Neuropeptide Y

Y₁	Agonists: Neuropeptide Y Peptide YY Antagonists: BIBP-3226

Y₂	Agonists: Neuropeptide Y Peptide YY Antagonists: BIIE-0246

Y₄	Agonists: Neuropeptide Y Pancreatic polypeptide Peptide YY Antagonists: UR-AK49

Y₅	Agonists: Neuropeptide Y Peptide YY Antagonists: Lu AA-33810

Neurotensin

NTS₁	Agonists: Neurotensin Neuromedin N Antagonists: SR-48692 SR-142,948

NTS₂	Agonists: Neurotensin Antagonists: Levocabastine SR-142,948

Orexin

OX₁	Agonists: Orexin-A Antagonists: Almorexant SB-334,867 SB-408,124 SB-649,868 Suvorexant

OX₂	Agonists: Orexin-A Antagonists: Almorexant SB-649,868 Suvorexant TCS-OX2-29

Oxytocin

Tachykinin

NK₁	Agonists: Substance P Antagonists: Aprepitant Befetupitant Casopitant CI-1021 CP-96,345 CP-99,994 CP-122,721 Dapitant Ezlopitant FK-888 Fosaprepitant GR-203,040 GW-597,599 HSP-117 L-733,060 L-741,671 L-743,310 L-758,298 Lanepitant LY-306,740 Maropitant Netupitant NKP-608 Nolpitantium Orvepitant RP-67,580 SDZ NKT 343 Vestipitant Vofopitant

NK₂	Agonists: Neurokinin A Antagonists: GR-159,897 Ibodutant Saredutant

NK₃	Agonists: Neurokinin B Antagonists: Osanetant Talnetant

Vasopressin

V_1A	Agonists: Desmopressin Felypressin Ornipressin Terlipressin Vasopressin Antagonists: Conivaptan Demeclocycline Relcovaptan

V_1B	Agonists: Felypressin Ornipressin Terlipressin Vasopressin Antagonists: Demeclocycline Nelivaptan

V₂	Agonists: Desmopressin Ornipressin Vasopressin Antagonists: Conivaptan Demeclocycline Lixivaptan Mozavaptan Satavaptan Tolvaptan

This drug article relating to the gastrointestinal system is a stub. You can help Wikipedia by expanding it.

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

Original courtesy of Wikipedia: http://en.wikipedia.org/wiki/L-733,060 — Please support Wikipedia.
A portion of the proceeds from advertising on Digplanet goes to supporting Wikipedia.

L-733,060

See also [edit]

References [edit]

Talk About L-733,060

Support Wikipedia