Inibidor de recaptação de serotonina-noradrenalina-dopamina

Os inibidores de recaptação de serotonina-noradrenalina-dopamina (SNDRIs), também conhecidos como inibidores triplos de recaptação (TRI), são uma classe farmacológica composta por drogas que inibem a recaptação dos neurotransmissores monoamínicos: serotonina, noradrenalina e dopamina.

Seu mecanismo de ação inibe, ao mesmo tempo, a recaptação neuronal do transportador de serotonina (SERT), noradrenalina (NET) e o dopamina (DAT). A inibição da recaptação desses neurotransmissores aumenta suas concentrações extracelulares e, portanto, estimulam a neurotransmissão serotoninérgica, noradrenérgica e dopaminérgica.

Usos clínicos

Depressão

O transtorno depressivo maior (TDM) é uma das principais patologias que sustentam a necessidade de desenvolvimento dos SNDRIs. De acordo com a Organização Mundial da Saúde (OMS), em 2006 a depressão foi a principal causa de deficiências e a quarta maior responsável pela Carga Global de Morbidade (CGM). Estima-se que a depressão atinga a segunda posição no ranking de esperança de vida corrigida pela incapacidade por volta de 2020.

Farmacoterapia

Os SNDRIs são utilizados quando outros fármacos não produzem os efeitos terapêuticos esperados, como em casos de depressão resistente a tratamento. Embora dois terços das pessoas respondam adequadamento ao tratamento com outros antidepressivos, um terço das pessoas responde ao placebo, e a taxa de recidiva (remissão incompleta_ devido aos sintomas de rebote são altas. Além da altaxa taxa de remissão pós-tratamento, os sintomas depressivos podem reaparecer mesmo ao decorrer das terapias de longo prazo (taquifilaxia). Além disso, os antidepressivos disponíveis atualmente provocam efeitos colaterais indesejáveis, de modo que a pesquisa médica busca compostos com menor potencial de efeitos adversos a fim de diminuir as recidivas ou desistências de tratamento.

Outros

Lista de SNDRIs

Fármacos aprovados

SNDRIs fracos

Ensaios clínicos em andamento

  • Amitifadina (DOV-21.947, EB-1010) (2003)
  • AN788 (anteriormente NSD-788) - veja aqui para detalhes
  • Ansofaxina (LY03005 / LPM570065)
  • Centanafadina (EB-1020) - veja aqui os detalhes da proporção de 1 a 6 a 14 para NDS
  • Dasotralina (SEP-225,289)
  • Lu AA34893 - veja aqui (modulador SNDRI e 5-HT 2A, α 1 e 5-HT 6 )
  • Lu AA37096 - veja aqui (modulador SNDRI e 5-HT 6 )
  • NS-2360 - principal metabólito de tesofensina
  • Tedatioxetina (Lu AA24530) - SNDRI e modulador 5-HT 2C, 5-HT 3, 5-HT 2A e α 1
  • Tesofensina (NS-2330) (2001)

Ensaios clínicos interrompidos

  • Bicifadina (DOV-220.075) - interrompido em 1981
  • BMS-866.949
  • Brasofensina (NS-2214, BMS-204,756) (1995)
  • Diclofensina (Ro 8-4650) (1982)
  • DOV-216.303 (2004)
  • EXP-561 (1965)
  • Liafensina (BMS-820.836)
  • NS-2359 (GSK-372.475)
  • RG-7166 (2009–2012)

Drogas projetadas

  • 3-Metil-PCPy
  • Nafirona (O-2482, naftilpirovalerona, NRG-1) (2006)

Compostos pesquisados (não testados em humanos)

  • 3,3-Difenilciclobutanamina (1978)
  • 3,4-Diclorotametralina (trans-(1R,4S)-sertralina ) (1980)
  • D-161 (2008)
  • Desmetilsertralina - metabólito ativo da sertralina; afinidade 76 nM para SERT, 420 nM para NET, 440 nM para DAT
  • DMNPC (2000)
  • DOV-102.677 (2006–2011)
  • GSK1360707F (2010)
  • Indatralina (1985)
  • JNJ-7925476 (2008; apareceu pela primeira vez em 1987)
  • JZ-IV-10 (2005)
  • JZAD-IV-22 (2010)
  • LR-5182 (1978)
  • Metilnaftidato (HDMP-28) (2001)
  • MI-4
  • PRC200-SS (2008)
  • SKF-83.959 (2013)
  • TP1 (2011)
  • Vários feniltropanos, como WF-23, dicloropano e RTI-55
  • NS9775

Extratos botânicos

Referências

  1. ↑ Millan, MJ (2009). «Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: Novel concepts, new drugs». Neurotherapeutics. 6: 53–77. PMC 5084256Acessível livremente. PMID 19110199. doi:10.1016/j.nurt.2008.10.039
  2. ↑ Kulkarni, SK; Dhir, A (2009). «Current investigational drugs for major depression». Expert Opinion on Investigational Drugs. 18: 767–88. PMID 19426122. doi:10.1517/13543780902880850
  3. ↑ Guiard, BP; El Mansari, M; Blier, P (2009). «Prospect of a dopamine contribution in the next generation of antidepressant drugs: The triple reuptake inhibitors». Current Drug Targets. 10: 1069–84. PMID 19702555. doi:10.2174/138945009789735156
  4. ↑ Marks, DM; Pae, CU; Patkar, AA (2008). «Triple reuptake inhibitors: The next generation of antidepressants». Current Neuropharmacology. 6: 338–43. PMC 2701280Acessível livremente. PMID 19587855. doi:10.2174/157015908787386078
  5. 1 2 Chen, Z; Skolnick, P (2007). «Triple uptake inhibitors: Therapeutic potential in depression and beyond». Expert Opinion on Investigational Drugs. 16: 1365–77. PMID 17714023. doi:10.1517/13543784.16.9.1365
  6. 1 2 Millan, MJ (2006). «Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application». Pharmacology & Therapeutics. 110: 135–370. PMID 16522330. doi:10.1016/j.pharmthera.2005.11.006
  7. ↑ Perona, MT; Waters, S; Hall, FS; Sora, I; Lesch, KP; Murphy, DL; Caron, M; Uhl, GR (2008). «Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: Prominent effects of dopamine transporter deletions». Behavioural Pharmacology. 19: 566–74. PMC 2644662Acessível livremente. PMID 18690111. doi:10.1097/FBP.0b013e32830cd80f
  8. ↑ Chen, Z; Yang, J; Tobak, A (2008). «Designing new treatments for depression and anxiety». IDrugs : The Investigational Drugs Journal. 11: 189–97. PMID 18311656
  9. ↑ Perović, B; Jovanović, M; Miljković, B; Vezmar, S (2010). «Getting the balance right: Established and emerging therapies for major depressive disorders». Neuropsychiatric Disease and Treatment. 6: 343–64. PMC 2938284Acessível livremente. PMID 20856599. doi:10.2147/ndt.s10485
  10. ↑ Rakofsky, JJ; Holtzheimer, PE; Nemeroff, CB (2009). «Emerging targets for antidepressant therapies». Current Opinion in Chemical Biology. 13: 291–302. PMC 4410714Acessível livremente. PMID 19501541. doi:10.1016/j.cbpa.2009.04.617
  11. ↑ «Depression». World Health Organization. WHO. Cópia arquivada em 21 de julho de 2010
  12. ↑ Belmaker, RH (2008). «The future of depression psychopharmacology». CNS Spectrums. 13: 682–7. PMID 18704023. doi:10.1017/S1092852900013766
  13. 1 2 Yang, AR; Yi, HS; Warnock, KT; Mamczarz, J; June Jr, HL; Mallick, N; Krieter, PA; Tonelli, L; et al. (2012). «Effects of the Triple Monoamine Uptake Inhibitor DOV 102,677 on Alcohol-Motivated Responding and Antidepressant Activity in Alcohol-Preferring (P) Rats». Alcoholism: Clinical and Experimental Research. 36: 863–73. PMC 3464941Acessível livremente. PMID 22150508. doi:10.1111/j.1530-0277.2011.01671.x
  14. ↑ McMillen, BA; Shank, JE; Jordan, KB; Williams, HL; Basile, AS (2007). «Effect of DOV 102,677 on the volitional consumption of ethanol by Myers' high ethanol-preferring rat». Alcoholism: Clinical and Experimental Research. 31: 1866–71. PMID 17908267. doi:10.1111/j.1530-0277.2007.00513.x
  15. ↑ Gardner, Eliot L.; Liu, Xinhe; Paredes, William; Giordano, Anthony; Spector, Jordan; Lepore, Marino; Wu, Kuo-Ming; Froimowitz, Mark (2006). «A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: Effects in laboratory rat models relating to addiction». Neuropharmacology. 51: 993–1003. PMID 16901516. doi:10.1016/j.neuropharm.2006.06.009
  16. ↑ Tizzano, JP; Stribling, DS; Perez-Tilve, D; Strack, A; Frassetto, A; Chen, RZ; Fong, TM; Shearman, L; et al. (2008). «The triple uptake inhibitor (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo3.1.0 hexane hydrochloride (DOV 21947) reduces body weight and plasma triglycerides in rodent models of diet-induced obesity». The Journal of Pharmacology and Experimental Therapeutics. 324: 1111–26. PMID 18089843. doi:10.1124/jpet.107.133132
  17. ↑ http://clinicaltrials.gov/ct2/show/NCT00467428
  18. ↑ Basile, AS; Janowsky, A; Golembiowska, K; Kowalska, M; Tam, E; Benveniste, M; Popik, P; Nikiforuk, A; et al. (2007). «Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain». The Journal of Pharmacology and Experimental Therapeutics. 321: 1208–25. PMID 17325229. doi:10.1124/jpet.106.116483
  19. 1 2 Zoran Rankovic; Richard Hargreaves; Matilda Bingham (2012). Drug Discovery for Psychiatric Disorders. [S.l.]: Royal Society of Chemistry. pp. 199–200. ISBN 978-1-84973-365-6
  20. ↑ Kim, K A; Song, W K; Park, J Y (2009). «Association of CYP2B6, CYP3A5, and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects». Clinical Pharmacology & Therapeutics. 86: 511–518. ISSN 0009-9236. PMID 19693007. doi:10.1038/clpt.2009.145
  21. ↑ Hofbauer, Karl (2004). Pharmacotherapy of obesity : options and alternatives. Boca Raton, Fla: CRC Press. ISBN 978-0-415-30321-7
  22. ↑ Douglas S. Johnson; Jie Jack Li (26 de fevereiro de 2013). The Art of Drug Synthesis. [S.l.]: John Wiley & Sons. pp. 13–. ISBN 978-1-118-67846-6
  23. ↑ Wellington K, Perry CM (2001). «Venlafaxine extended-release: a review of its use in the management of major depression». CNS Drugs. 15: 643–69. PMID 11524036. doi:10.2165/00023210-200115080-00007
  24. ↑ Ahmadi, A; Khalili, M; Marami, S; Ghadiri, A; Nahri-Niknafs, B (2014). «Synthesis and pain perception of new analogues of phencyclidine in NMRI male mice». Mini Reviews in Medicinal Chemistry. 14: 64–71. PMID 24251803. doi:10.2174/1389557513666131119203551
  25. ↑ Oishi R, Shishido S, Yamori M, Saeki K (fevereiro de 1994). «Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain». Naunyn-Schmiedeberg's Archives of Pharmacology. 349: 140–4. PMID 7513381. doi:10.1007/bf00169830
  26. ↑ Sato T, Suemaru K, Matsunaga K, Hamaoka S, Gomita Y, Oishi R (maio de 1996). «Potentiation of L-dopa-induced behavioral excitement by histamine H1-receptor antagonists in mice». Japanese Journal of Pharmacology. 71: 81–4. PMID 8791174. doi:10.1254/jjp.71.81
  27. ↑ Yeh SY, Dersch C, Rothman R, Cadet JL (setembro de 1999). «Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats». Synapse. 33: 207–17. PMID 10420168. doi:10.1002/(SICI)1098-2396(19990901)33:3<207::AID-SYN5>3.0.CO;2-8
  28. ↑ David Healy (janeiro de 2004). Let them eat Prozac: the unhealthy ... - Google Books. [S.l.: s.n.] ISBN 978-0-8147-3669-2
  29. ↑ Skolnick, P; Popik, P; Janowsky, A; Beer, B; Lippa, AS (2003). «Antidepressant-like actions of DOV 21,947: A "triple" reuptake inhibitor». European Journal of Pharmacology. 461: 99–104. PMID 12586204. doi:10.1016/S0014-2999(03)01310-4
  30. ↑ Golembiowska, K; Kowalska, M; Bymaster, FP (2012). «Effects of the triple reuptake inhibitor amitifadine on extracellular levels of monoamines in rat brain regions and on locomotor activity». Synapse. 66: 435–44. PMID 22213370. doi:10.1002/syn.21531
  31. ↑ Tran, P; Skolnick, P; Czobor, P; Huang, NY; Bradshaw, M; McKinney, A; Fava, M (2012). «Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial». Journal of Psychiatric Research. 46: 64–71. PMID 21925682. doi:10.1016/j.jpsychires.2011.09.003
  32. ↑ Zhang, R.; Li, X.; Shi, Y.; Shao, Y.; Sun, K.; Wang, A.; Sun, F.; Liu, W.; Wang, D. (2014). «The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats». PLoS ONE. 9: e91775. Bibcode:2014PLoSO...991775Z. PMC 3948889Acessível livremente. PMID 24614602. doi:10.1371/journal.pone.0091775
  33. ↑ Delorenzo, C; Lichenstein, S; Schaefer, K; Dunn, J; Marshall, R; Organisak, L; Kharidia, J; Robertson, B; et al. (2011). «SEP-225289 serotonin and dopamine transporter occupancy: A PET study». Journal of Nuclear Medicine. 52: 1150–5. PMC 3856248Acessível livremente. PMID 21680689. doi:10.2967/jnumed.110.084525
  34. ↑ «Dasotraline Adult ADHD Study»
  35. ↑ «Development programme - Lundbeck»
  36. ↑ «Search of: Lu AA24530 - List Results - ClinicalTrials.gov»
  37. ↑ Epstein, JW; Brabander, HJ; Fanshawe, WJ; Hofmann, CM; McKenzie, TC; Safir, SR; Osterberg, AC; Cosulich, DB; Lovell, FM (1981). «1-Aryl-3-azabicyclo3.1.0hexanes, a new series of nonnarcotic analgesic agents». Journal of Medicinal Chemistry. 24: 481–90. PMID 7241504. doi:10.1021/jm00137a002
  38. ↑ Xu, Feng; Murry, Jerry A.; Simmons, Bryon; Corley, Edward; Fitch, Kenneth; Karady, Sandor; Tschaen, David (2006). «Stereocontrolled Synthesis of Trisubstituted Cyclopropanes: Expedient, Atom-Economical, Asymmetric Syntheses of (+)-Bicifadine and DOV21947». Organic Letters. 8: 3885–8. PMID 16898842. doi:10.1021/ol061650w
  39. ↑ EP 0756596
  40. ↑ Keller, HH; Schaffner, R; Carruba, MO; Burkard, WP; Pieri, M; Bonetti, EP; Scherschlicht, R; Da Prada, M; Haefely, WE (1982). «Diclofensine (Ro 8-4650)--a potent inhibitor of monoamine uptake: Biochemical and behavioural effects in comparison with nomifensine». Advances in Biochemical Psychopharmacology. 31: 249–63. PMID 6979165
  41. ↑ Omer, LM (1982). «Pilot trials with diclofensine, a new psychoactive drug in depressed patients». International Journal of Clinical Pharmacology, Therapy, and Toxicology. 20: 320–6. PMID 7107085
  42. ↑ Beer, B; Stark, J; Krieter, P; Czobor, P; Beer, G; Lippa, A; Skolnick, P (2004). «DOV 216,303, a "triple" reuptake inhibitor: Safety, tolerability, and pharmacokinetic profile». Journal of Clinical Pharmacology. 44: 1360–7. PMID 15545306. doi:10.1177/0091270004269560
  43. ↑ Prins, J; Westphal, KG; Korte-Bouws, GA; Quinton, MS; Schreiber, R; Olivier, B; Korte, SM (2011). «The potential and limitations of DOV 216,303 as a triple reuptake inhibitor for the treatment of major depression: A microdialysis study in olfactory bulbectomized rats». Pharmacology Biochemistry and Behavior. 97: 444–52. PMID 20934452. doi:10.1016/j.pbb.2010.10.001
  44. ↑ Patente E.U.A. 3 308 160PHENYLBICYCLO[Z.Z.Z]OCTANE-L-AMINES AND SALTS THEREOF.
  45. ↑ Learned, S; Graff, O; Roychowdhury, S; Moate, R; Krishnan, KR; Archer, G; Modell, JG; Alexander, R; et al. (2012). «Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: Two randomized, placebo- and active-controlled clinical trials». Journal of Psychopharmacology (Oxford, England). 26: 653–62. PMID 22048884. doi:10.1177/0269881111424931
  46. ↑ Wallach J, Brandt SD (2018). «Phencyclidine-Based New Psychoactive Substances». Handb Exp Pharmacol. 252: 261–303. PMID 30105474. doi:10.1007/164_2018_124
  47. ↑ Meltzer, PC; Butler, D; Deschamps, JR; Madras, BK (2006). «1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: A promising class of monoamine uptake inhibitors». Journal of Medicinal Chemistry. 49: 1420–32. PMC 2602954Acessível livremente. PMID 16480278. doi:10.1021/jm050797a
  48. ↑ Alan Travis, home affairs editor (1 de abril de 2010). «NRG-1 may be next legal high to face ban by ministers | Politics». The Guardian. Consultado em 3 de abril de 2010
  49. ↑ Carroll, FI; Lewin, AH; Mascarella, SW; Seltzman, HH; Reddy, PA (2012). «Designer drugs: A medicinal chemistry perspective». Annals of the New York Academy of Sciences. 1248: 18–38. Bibcode:2012NYASA1248...18C. PMID 22092008. doi:10.1111/j.1749-6632.2011.06199.x
  50. ↑ Carnmalm, B; Rämsby, S; Renyi, AL; Ross, SB; Ogren, SO; Stjernstrom, Nils E. (1978). «Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants». Journal of Medicinal Chemistry. 21: 78–82. PMID 22757. doi:10.1021/jm00199a014
  51. ↑ Patente E.U.A. 4 556 676
  52. ↑ Dutta, AK; Ghosh, B; Biswas, S; Reith, ME (2008). «D-161, a novel pyran-based triple monoamine transporter blocker: Behavioral pharmacological evidence for antidepressant-like action». European Journal of Pharmacology. 589: 73–9. PMID 18561912. doi:10.1016/j.ejphar.2008.05.008
  53. ↑ Wong DT, Bymaster FP, Engleman EA (1995). «Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication». Life Sci. 57: 411–41. PMID 7623609. doi:10.1016/0024-3205(95)00209-o
  54. ↑ Tamiz, AP; Zhang, J; Flippen-Anderson, JL; Zhang, M; Johnson, KM; Deschaux, O; Tella, S; Kozikowski, AP (2000). «Further SAR studies of piperidine-based analogues of cocaine. 2. Potent dopamine and serotonin reuptake inhibitors». Journal of Medicinal Chemistry. 43: 1215–22. PMID 10737754. doi:10.1021/jm9905561
  55. ↑ Deschamps, NM; Elitzin, VI; Liu, B; Mitchell, MB; Sharp, MJ; Tabet, EA (2011). «An enyne cycloisomerization approach to the triple reuptake inhibitor GSK1360707F». The Journal of Organic Chemistry. 76: 712–5. PMID 21174473. doi:10.1021/jo102098y
  56. ↑ Micheli, F; Cavanni, P; Andreotti, D; Arban, R; Benedetti, R; Bertani, B; Bettati, M; Bettelini, L; et al. (2010). «6-(3,4-dichlorophenyl)-1-(methyloxy)methyl-3-azabicyclo4.1.0heptane: A new potent and selective triple reuptake inhibitor». Journal of Medicinal Chemistry. 53: 4989–5001. PMID 20527970. doi:10.1021/jm100481d
  57. ↑ Bøgesø, KP; Christensen, AV; Hyttel, J; Liljefors, T (1985). «3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake». Journal of Medicinal Chemistry. 28: 1817–28. PMID 2999402. doi:10.1021/jm00150a012
  58. ↑ Aluisio, L; Lord, B; Barbier, AJ; Fraser, IC; Wilson, SJ; Boggs, J; Dvorak, LK; Letavic, MA; et al. (2008). «In-vitro and in-vivo characterization of JNJ-7925476, a novel triple monoamine uptake inhibitor». European Journal of Pharmacology. 587: 141–6. PMID 18499098. doi:10.1016/j.ejphar.2008.04.008
  59. ↑ WO 2005041875
  60. ↑ Caldarone, BJ; Paterson, NE; Zhou, J; Brunner, D; Kozikowski, AP; Westphal, KG; Korte-Bouws, GA; Prins, J; et al. (2010). «The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties». The Journal of Pharmacology and Experimental Therapeutics. 335: 762–70. PMC 2993553Acessível livremente. PMID 20864506. doi:10.1124/jpet.110.174011
  61. ↑ Wong, DT; Bymaster, FP (1978). «An inhibitor of dopamine uptake, LR5182, cis-3-(3,4-dichlorophenyl)-2-n,n-dimethylaminomethyl-bicyclo-2,2,2-octane, hydrochloride». Life Sciences. 23: 1041–7. PMID 713683. doi:10.1016/0024-3205(78)90664-1
  62. ↑ Fuller, RW; Perry, KW; Snoddy, HD (1979). «In vivo effects of LR5182, cis-3-(3,4-dichlorophenyl)-2-n,n-dimethylaminomethyl- bicyclo-2,2,2-octane hydrochloride, an inhibitor of uptake into dopamine and norepinephrine neurons». Neuropharmacology. 18: 497–501. PMID 460546. doi:10.1016/0028-3908(79)90076-5
  63. ↑ Wong, DT; Bymaster, FP; Reid, LR (1980). «Competitive inhibition of catecholamine uptake in synaptosomes of rat brain by rigid bicyclo-octanes». Journal of Neurochemistry. 34: 1453–8. PMID 7381469. doi:10.1111/j.1471-4159.1980.tb11225.x
  64. ↑ Lile, JA; Wang, Z; Woolverton, WL; France, JE; Gregg, TC; Davies, HM; Nader, MA (2003). «The reinforcing efficacy of psychostimulants in rhesus monkeys: The role of pharmacokinetics and pharmacodynamics». The Journal of Pharmacology and Experimental Therapeutics. 307: 356–66. PMID 12954808. doi:10.1124/jpet.103.049825
  65. ↑ Criado, Elisa (2 de maio de 2014). «A fast-acting antidepressant could be on the horizon». The Independent. Consultado em 22 de junho de 2014
  66. ↑ http://www.fasebj.org/content/28/1_Supplement/1144.1.short
  67. ↑ Liang, Y; Shaw, AM; Boules, M; Briody, S; Robinson, J; Oliveros, A; Blazar, E; Williams, K; et al. (2008). «Antidepressant-like pharmacological profile of a novel triple reuptake inhibitor, (1S,2S)-3-(methylamino)-2-(naphthalen-2-yl)-1-phenylpropan-1-ol (PRC200-SS)». The Journal of Pharmacology and Experimental Therapeutics. 327: 573–83. PMID 18689611. doi:10.1124/jpet.108.143610
  68. ↑ Fang, X.; Guo, L.; Jia, J.; Jin, G. Z.; Zhao, B.; Zheng, Y. Y.; Li, J. Q.; Zhang, A.; Zhen, X. C. (2013). «SKF83959 is a novel triple reuptake inhibitor that elicits anti-depressant activity». Acta Pharmacologica Sinica. 34: 1149–55. PMC 4003162Acessível livremente. PMID 23892272. doi:10.1038/aps.2013.66
  69. ↑ Tian, JW; Jiang, WL; Zhong, Y; Meng, Q; Gai, Y; Zhu, HB; Hou, J; Xing, Y; Li, YX (2011). «Preclinical pharmacology of TP1, a novel potent triple reuptake inhibitor with antidepressant properties». Neuroscience. 196: 124–30. PMID 21925241. doi:10.1016/j.neuroscience.2011.08.064
  70. ↑ Carroll, FI (2003). «2002 Medicinal Chemistry Division Award address: Monoamine transporters and opioid receptors. Targets for addiction therapy». Journal of Medicinal Chemistry. 46: 1775–94. PMID 12723940. doi:10.1021/jm030092d
  71. ↑ Andreasen, Jesper T.; Redrobe, John P.; Nielsen, Elsebet Ø.; Christensen, Jeppe K.; Olsen, Gunnar M.; Peters, Dan (2013). «A combined α7 nicotinic acetylcholine receptor agonist and monoamine reuptake inhibitor, NS9775, represents a novel profile with potential benefits in emotional and cognitive disturbances». Neuropharmacology. 73: 183–191. ISSN 0028-3908. PMID 23748055. doi:10.1016/j.neuropharm.2013.04.060
  72. ↑ Fehske, C. J.; Leuner, K.; Müller, W. E. (2009). «Ginkgo biloba extract (EGb761®) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment». Pharmacological Research. 60: 68–73. PMID 19427589. doi:10.1016/j.phrs.2009.02.012
  73. ↑ Mechan, Annis O.; Fowler, Ann; Seifert, Nicole; Rieger, Henry; Wöhrle, Tina; Etheve, Stéphane; Wyss, Adrian; Schüler, Göde; Colletto, Biagio (2010). «Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract». British Journal of Nutrition. 105: 1150–1163. ISSN 0007-1145. PMID 21205415. doi:10.1017/S0007114510004940
  74. ↑ Sasaki, Kazunori; El Omri, Abdelfatteh; Kondo, Shinji; Han, Junkyu; Isoda, Hiroko (2013). «Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation». Behavioural Brain Research. 238: 86–94. ISSN 0166-4328. PMID 23085339. doi:10.1016/j.bbr.2012.10.010
  75. ↑ Jin, Zeng-Liang; Gao, Nana; Zhou, Dan; Chi, Mu-Gen; Yang, Xue-Mei; Xu, Jiang-Ping (2012). «The extracts of Fructus Akebiae, a preparation containing 90% of the active ingredient hederagenin: Serotonin, norepinephrine and dopamine reuptake inhibitor». Pharmacology Biochemistry and Behavior. 100: 431–439. ISSN 0091-3057. PMID 22005599. doi:10.1016/j.pbb.2011.10.001