Jump to content

Serotonin–norepinephrine–dopamine reuptake inhibitor

From Wikipedia, the free encyclopedia
(Redirected from Triple reuptake inhibitor)

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI or TUI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine, resulting in increased signaling in associated neurological systems.

SNDRIs were developed as potential antidepressants and treatments for other disorders, such as obesity, cocaine addiction, attention-deficit hyperactivity disorder (ADHD), and chronic pain.[1] The goal of such development was improved efficacy or tolerability over existing selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and dopamine-norepinephrine reuptake inhibitors (NDRIs).[1] However, increased side effects and abuse potential are concerns when using these agents, relative to their more selective counterparts.

SNDRIs include the naturally occurring drug cocaine, a widely used recreational and often illegal drug for the euphoric effects it produces.[2] Additionally, MDMA, another common drug of abuse, is also an SNDRI, however its reuptake inhibition is comparatively weak compared to its properties as a serotonin-dopamine-norepinephrine releasing agent. [3][4][5][6][7]

Indications

[edit]

SNDRIs have been studied for a number of indications, but primarily for that of depression, and ADHD.

Preclinical and clinical research indicates that drugs inhibiting the reuptake of all three of these neurotransmitters can produce a more rapid onset of action and greater efficacy than traditional antidepressants.[8]

Applications other than depression

[edit]

Cocaine

[edit]
Cocaine in powder form.

Cocaine is a short-acting SNDRI that also exerts auxiliary pharmacological actions on other receptors.[2] Cocaine is a relatively "balanced" inhibitor, although facilitation of dopaminergic neurotransmission is what has been linked to the reinforcing and addictive effects. Cocaine users may experience symptoms of extreme fatigue, decreased mood, and a "crash" following the original euphoria of the drug; subsequent to the crash, users begin to crave for more.[15] In addition, cocaine has some serious limitations in terms of its cardiotoxicity due to its local anesthetic activity.[16] Thousands of cocaine users are admitted to emergency units in the USA every year because of this; thus, development of safer substitute medications for cocaine abuse could potentially have significant benefits for public health.[17]

Many of the SNDRIs currently being developed have varying degrees of similarity to cocaine in terms of their chemical structure.[18] There has been speculation over whether the new SNDRIs will have an abuse potential like cocaine does. However, for pharmacotherapeutics, treatment of cocaine addiction is advantageous if a substitute medication is at least weakly reinforcing because it can serve to retain addicts in treatment programs.[19]

... limited reinforcing properties in the context of treatment programs may be advantageous, contributing to improved patient compliance and enhanced medication effectiveness.[20]

Legality

[edit]
Cocaine can be used as a local anesthetic for certain surgeries.[21]

Cocaine is a controlled drug (Class A in the UK; Schedule II in the USA); it has not been entirely outlawed in most countries, as despite having some "abuse potential" it is recognized as useful for surgery considering it is a local anesthetic that can be applied to areas such as the nose, mouth, or throat for numbing purposes.[21]

Brasofensine, a dopamine inhibitor developed to treat Parkinson's disease, was made "class A" in the UK under the MDA (misuse of drugs act). The semi-synthetic procedure for making brasofensine uses cocaine as the starting material.[22]

Naphyrone, a drug that inhibits monoamine transporters, first appeared in 2006 as one of quite a large number of analogs of pyrovalerone designed by the well-known medicinal chemist P. Meltzer et al.[23] When the designer drugs mephedrone and methylone became banned in the United Kingdom, vendors of these chemicals needed to find a suitable replacement. Mephedrone and methylone affect the same chemicals in the brain as a SNDRI, although they are thought to act as monoamine releasers and not act through the reuptake inhibitor mechanism of activity. A short time later, mephedrone and methylone were banned (which had become quite popular by the time they were illegalized), naphyrone appeared under the trade name NRG-1. NRG-1 was promptly illegalized, although it is not known if its use resulted in any hospitalizations or deaths.[24][25]

Self-Administration of Drugs

[edit]

According to various studies, the relative likelihood of rodents and non-human primates self-administering various psychostimulants that modulate monoaminergic neurotransmission is lessened as the dopaminergic compounds become more serotonergic.[26] This finding has been found for amphetamine and some of its variously substituted analogs including PAL-287 etc. RTI-112 is another good example of the compound becoming less likely to be self-administered by the test subject in the case of a dopaminergic compound that also has a marked affinity for the serotonin transporter.[27]

Further evidence that 5-HT (serotonin) dampens the reinforcing actions of dopaminergic medications comes from the co-administration of psychostimulants with SSRIs, and the phen/fen combination was also shown to have limited abuse potential relative to administration of phentermine only.[28] However, not all SNDRIs are reliably self-administered by animals. Examples include:

  • PRC200-SS was not reliably self-administered.[29]
  • RTI-112 was not self-administered[30] because at low doses the compound preferentially occupies the SERT and not the DAT.[31][32]
  • Tesofensine was also not reliably self-administered by human stimulant addicts.[33]
  • The nocaine analog JZAD-IV-22 only partly substituted for cocaine in animals, but produced none of the psychomotor activation of cocaine, which is a trait marker for stimulant addiction.[34]

Failure of SNDRIs for depression

[edit]

SNDRIs have been under investigation for the treatment of major depressive disorder for a number of years but, as of 2015, have failed to meet effectiveness expectations in clinical trials.[35] In addition, the augmentation of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor with lisdexamfetamine, a norepinephrine–dopamine releasing agent, recently failed to separate from placebo in phase III clinical trials of individuals with treatment-resistant depression, and clinical development was subsequently discontinued.[35] These occurrences have shed doubt on the potential benefit of dopaminergic augmentation of conventional serotonergic and noradrenergic antidepressant therapy.[35] As such, skepticism has been cast on the promise of the remaining SNDRIs that are still being trialed, such as ansofaxine (currently in phase II trials), in the treatment of depression.[35] Despite being a weak SNDRI, nefazodone has been successful in treating major depressive disorder.[36]

Known SNDRIS

[edit]

Approved pharmaceuticals

[edit]

Sibutramine (Meridia) is a withdrawn anorectic that is an SNDRI in vitro with ki values of 298 nM at SERT, 5451 at NET, 943 nM at DAT.[37] However, it appears to act as a prodrug in vivo to metabolites that are considerably more potent and possess different ratios of monoamine reuptake inhibition in comparison, and in accordance, sibutramine behaves contrarily as an SNRI (73% and 54% for norepinephrine and serotonin reuptake inhibition, respectively) in human volunteers with only very weak and probably inconsequential inhibition of dopamine reuptake (16%).[42][43][1]

Venlafaxine (Effexor) is sometimes referred to as an SNDRI, but is extremely imbalanced with ki values of 82 nM for SERT, 2480 nM for NET, and 7647 nM for DAT, with a ratio of 1:30:93.[44] It may weakly inhibit the reuptake of dopamine at high doses.[45]

Coincidental

[edit]

Undergoing clinical trials

[edit]
SEP-432

Failed clinical trials

[edit]

Designer drugs

[edit]

Research compounds (no record of having been taken by humans)

[edit]
3,4-Diphenylpiperidine
MDL 47,832
3,4-Diphenylquinuclidine

Herbals

[edit]

See also

[edit]

References

[edit]
  1. ^ a b Sharma, Horrick; Santra, Soumava; Dutta, Aloke (November 2015). "Triple Reuptake Inhibitors as Potential Next-Generation Antidepressants: A New Hope?". Future Medicinal Chemistry. 7 (17): 2385–2406. doi:10.4155/fmc.15.134. ISSN 1756-8919. PMC 4976848. PMID 26619226.
  2. ^ a b Elfers, K.; Menne, L.; Colnaghi, L.; Hoppe, S.; Mazzuoli-Weber, G. (2023). "Short- and Long-Term Effects of Cocaine on Enteric Neuronal Functions". Cells. 12 (4): 577. doi:10.3390/cells12040577. PMC 9954635. PMID 36831246.
  3. ^ Dunlap LE, Andrews AM, Olson DE (October 2018). "Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine" (PDF). ACS Chem Neurosci. 9 (10): 2408–2427. doi:10.1021/acschemneuro.8b00155. PMC 6197894. PMID 30001118.
  4. ^ Docherty JR, Alsufyani HA (August 2021). "Pharmacology of Drugs Used as Stimulants". J Clin Pharmacol. 61 (Suppl 2): S53–S69. doi:10.1002/jcph.1918. PMID 34396557. Receptor-mediated actions of amphetamine and other amphetamine derivatives [...] may involve trace amine-associated receptors (TAARs) at which amphetamine and MDMA also have significant potency.85–87 Many stimulants have potency at the rat TAAR1 in the micromolar range but tend to be about 5 to 10 times less potent at the human TAAR1, [...] Activation of the TAAR1 receptor causes inhibition of dopaminergic transmission in the mesocorticolimbic system, and TAAR1 agonists attenuated psychostimulant abuse-related behaviors.89 It is likely that TAARs contribute to the actions of specific stimulants to modulate dopaminergic, serotonergic, and glutamate signaling,90 and drugs acting on the TAAR1 may have therapeutic potential.91 In the periphery, stimulants such as MDMA and cathinone produce vasoconstriction, part of which may involve TAARs, although only relatively high concentrations produced vascular contractions resistant to a cocktail of monoamine antagonist drugs.86
  5. ^ Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". European Journal of Pharmacology. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID 14612135.
  6. ^ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID 17017961.
  7. ^ Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL (June 2003). "3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro". Molecular Pharmacology. 63 (6): 1223–1229. doi:10.1124/mol.63.6.1223. PMID 12761331. S2CID 839426.
  8. ^ Chen, Z; Yang, J; Tobak, A (2008). "Designing new treatments for depression and anxiety". IDrugs: The Investigational Drugs Journal. 11 (3): 189–97. PMID 18311656.
  9. ^ a b 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 (5): 863–73. doi:10.1111/j.1530-0277.2011.01671.x. PMC 3464941. PMID 22150508.
  10. ^ 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 (11): 1866–71. doi:10.1111/j.1530-0277.2007.00513.x. PMID 17908267.
  11. ^ 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 (5): 993–1003. doi:10.1016/j.neuropharm.2006.06.009. PMID 16901516. S2CID 20465584.
  12. ^ 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 (3): 1111–26. doi:10.1124/jpet.107.133132. PMID 18089843. S2CID 12020136.
  13. ^ "Efficacy and Safety of NS2359 in Adults with Attention Deficit Hyperactivity Disorder. A Randomised, Double-Blind, Placebo-Controlled Study". ClinicalTrials.gov. 27 April 2007.
  14. ^ 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 (3): 1208–25. doi:10.1124/jpet.106.116483. PMID 17325229. S2CID 17215882.
  15. ^ "Cocaine". DEA. Archived from the original on 2025-02-14. Retrieved 2025-03-03.
  16. ^ Pergolizzi Jr, J. V.; Magnusson, P.; Lequang, J. A.; Breve, F.; Varrassi, G. (2021). "Cocaine and Cardiotoxicity: A Literature Review". Cureus. 13 (4) e14594. doi:10.7759/cureus.14594. PMC 8136464. PMID 34036012.
  17. ^ Gangu, K.; Bobba, A.; Basida, S. D.; Avula, S.; Chela, H.; Singh, S. (2022). "Trends of Cocaine Use and Manifestations in Hospitalized Patients: A Cross-Sectional Study". Cureus. 14 (2) e22090. doi:10.7759/cureus.22090. PMC 8830384. PMID 35165645.
  18. ^ Elfers, Kristin; Menne, Laura; Colnaghi, Luca; Hoppe, Susanne; Mazzuoli-Weber, Gemma (2023-02-10). "Short- and Long-Term Effects of Cocaine on Enteric Neuronal Functions". Cells. 12 (4): 577. doi:10.3390/cells12040577. PMC 9954635. PMID 36831246.
  19. ^ Rush, Craig R; Stoops, William W (February 2012). "Agonist Replacement Therapy for Cocaine Dependence: A Translational Review". Future Medicinal Chemistry. 4 (2): 245–265. doi:10.4155/fmc.11.184. ISSN 1756-8919. PMC 3292908. PMID 22300101.
  20. ^ Howell, LL; Wilcox, KM (2001). "The dopamine transporter and cocaine medication development: Drug self-administration in nonhuman primates". The Journal of Pharmacology and Experimental Therapeutics. 298 (1): 1–6. doi:10.1016/S0022-3565(24)29344-7. PMID 11408518.
  21. ^ a b "Cocaine (topical route)". Mayo Clinic. Retrieved 2025-03-03.
  22. ^ PubChem. "Brasofensine". pubchem.ncbi.nlm.nih.gov. Retrieved 2025-03-03.
  23. ^ Pinterova-Leca, Nikola; Horsley, Rachel R.; Danda, Hynek; Žídková, Monika; Lhotková, Eva; Šíchová, Klára; Štefková, Kristýna; Balíková, Marie; Kuchař, Martin; Páleníček, Tomáš (March 2021). "Naphyrone (naphthylpyrovalerone): Pharmacokinetics, behavioural effects and thermoregulation in Wistar rats". Addiction Biology. 26 (2) e12906. doi:10.1111/adb.12906. ISSN 1369-1600. PMID 32378298.
  24. ^ Vardakou, Ioanna; Pistos, Constantinos; Dona, Artemis; Spiliopoulou, Chara; Athanaselis, Sotiris (October 2012). "Naphyrone: a "legal high" not legal any more". Drug and Chemical Toxicology. 35 (4): 467–471. doi:10.3109/01480545.2011.642381. ISSN 1525-6014. PMID 22168347.
  25. ^ López-Arnau, Raul; Martínez-Clemente, Jose; Pubill, David; Escubedo, Elena; Camarasa, Jorge (2012-08-22). "Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone". British Journal of Pharmacology. 167 (2): 407–420. doi:10.1111/j.1476-5381.2012.01998.x. ISSN 0007-1188. PMC 3481047. PMID 22509960.
  26. ^ Kohno, M.; Dennis, L. E.; McCready, H.; Hoffman, W. F. (2021). "Dopamine dysfunction in stimulant-use disorders: Mechanistic comparisons and implications for treatment". Molecular Psychiatry. 27 (1): 220–229. doi:10.1038/s41380-021-01180-4. PMC 8664889. PMID 34117366.
  27. ^ Negus, S.S.; Mello, N.K.; Kimmel, H.L.; Howell, L.L.; Carroll, F.I. (January 2009). "Effects of the monoamine uptake inhibitors RTI-112 and RTI-113 on cocaine- and food-maintained responding in rhesus monkeys". Pharmacology Biochemistry and Behavior. 91 (3): 333–338. doi:10.1016/j.pbb.2008.08.002. ISSN 0091-3057. PMC 2645592. PMID 18755212.
  28. ^ Baumann, M. H.; Ayestas, M. A.; Dersch, C. M.; Brockington, A.; Rice, K. C.; Rothman, R. B. (May 2000). "Effects of phentermine and fenfluramine on extracellular dopamine and serotonin in rat nucleus accumbens: therapeutic implications". Synapse (New York, N.Y.). 36 (2): 102–113. doi:10.1002/(SICI)1098-2396(200005)36:2<102::AID-SYN3>3.0.CO;2-#. ISSN 0887-4476. PMID 10767057.
  29. ^ a b 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 (2): 573–583. doi:10.1124/jpet.108.143610. PMID 18689611. S2CID 12635418.
  30. ^ Kimmel, HL; O'Connor, JA; Carroll, FI; Howell, LL (2007). "Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys". Pharmacology Biochemistry and Behavior. 86 (1): 45–54. doi:10.1016/j.pbb.2006.12.006. PMC 1850383. PMID 17258302.
  31. ^ a b Carroll FI (2003). "2002 Medicinal Chemistry Division Award address: Monoamine transporters and opioid receptors. Targets for addiction therapy". Journal of Medicinal Chemistry. 46 (10): 1775–94. doi:10.1021/jm030092d. PMID 12723940.
  32. ^ Lindsey, KP; Wilcox, KM; Votaw, JR; Goodman, MM; Plisson, C; Carroll, FI; Rice, KC; Howell, LL (2004). "Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: Relationship to transporter occupancy determined by positron emission tomography neuroimaging". The Journal of Pharmacology and Experimental Therapeutics. 309 (3): 959–69. doi:10.1124/jpet.103.060293. PMID 14982963. S2CID 39794215.
  33. ^ Schoedel, KA; Meier, D; Chakraborty, B; Manniche, PM; Sellers, EM (2010). "Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users". Clinical Pharmacology and Therapeutics. 88 (1): 69–78. doi:10.1038/clpt.2010.67. PMID 20520602. S2CID 39849071.
  34. ^ a b 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 (3): 762–770. doi:10.1124/jpet.110.174011. PMC 2993553. PMID 20864506.
  35. ^ a b c d Dale, Elena; Bang-Andersen, Benny; Sánchez, Connie (2015). "Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs". Biochemical Pharmacology. 95 (2): 81–97. doi:10.1016/j.bcp.2015.03.011. ISSN 0006-2952. PMID 25813654.
  36. ^ Davis, R.; Whittington, R.; Bryson, H. M. (April 1997). "Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression". Drugs. 53 (4): 608–636. doi:10.2165/00003495-199753040-00006. ISSN 0012-6667. PMID 9098663. S2CID 239077479.
  37. ^ a b Zoran Rankovic; Richard Hargreaves; Matilda Bingham (2012). Drug Discovery for Psychiatric Disorders. Royal Society of Chemistry. pp. 199–200. ISBN 978-1-84973-365-6.
  38. ^ Subbaiah, M. A. M. (22 March 2018). "Triple Reuptake Inhibitors as Potential Therapeutics for Depression and Other Disorders: Design Paradigm and Developmental Challenges". Journal of Medicinal Chemistry. 61 (6): 2133–65. doi:10.1021/acs.jmedchem.6b01827. PMID 28731336.
  39. ^ Zhang R, Li X, Shi Y, Shao Y, Sun K, Wang A, Sun F, Liu W, Wang D, Jin J, Li Y (2014). "The Effects of LPM570065, a Novel Triple Reuptake Inhibitor, on Extracellular Serotonin, Dopamine and Norepinephrine Levels in Rats". PLOS ONE. 9 (3). e91775. Bibcode:2014PLoSO...991775Z. doi:10.1371/journal.pone.0091775. PMC 3948889. PMID 24614602.
  40. ^ "NDA Filing for Luye Pharma's Antidepressant Drug LY03005 Accepted by the U.S. FDA — Press Releases — Luye Pharma Group". www.luye.cn. Retrieved 2022-06-11.
  41. ^ "Toludesvenlafaxine extended release - Luye Pharma". AdisInsight. Springer Nature Switzerland AG.
  42. ^ 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 (5): 511–8. doi:10.1038/clpt.2009.145. ISSN 0009-9236. PMID 19693007. S2CID 24789264.
  43. ^ Hofbauer, Karl (2004). Pharmacotherapy of obesity: options and alternatives. Boca Raton, Fla: CRC Press. ISBN 978-0-415-30321-7.
  44. ^ Douglas S. Johnson; Jie Jack Li (26 February 2013). The Art of Drug Synthesis. John Wiley & Sons. pp. 13–. ISBN 978-1-118-67846-6.
  45. ^ Wellington K, Perry CM (2001). "Venlafaxine extended-release: a review of its use in the management of major depression". CNS Drugs. 15 (8): 643–69. doi:10.2165/00023210-200115080-00007. PMID 11524036. S2CID 26795121.
  46. ^ 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 (1): 64–71. doi:10.2174/1389557513666131119203551. PMID 24251803.
  47. ^ Oishi R, Shishido S, Yamori M, Saeki K (February 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 (2): 140–4. doi:10.1007/bf00169830. PMID 7513381. S2CID 20653998.
  48. ^ Sato T, Suemaru K, Matsunaga K, Hamaoka S, Gomita Y, Oishi R (May 1996). "Potentiation of L-dopa-induced behavioral excitement by histamine H1-receptor antagonists in mice". Japanese Journal of Pharmacology. 71 (1): 81–4. doi:10.1254/jjp.71.81. PMID 8791174.
  49. ^ Yeh SY, Dersch C, Rothman R, Cadet JL (September 1999). "Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats". Synapse. 33 (3): 207–17. doi:10.1002/(SICI)1098-2396(19990901)33:3<207::AID-SYN5>3.0.CO;2-8. PMID 10420168. S2CID 16399789.
  50. ^ David Healy (January 2004). Let them eat Prozac: the unhealthy ... - Google Books. NYU Press. ISBN 978-0-8147-3669-2.
  51. ^ Southam E, Kirkby D, Higgins GA, Hagan RM (September 1998). "Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydroxytryptamine uptake in rats". European Journal of Pharmacology. 358 (1): 19–24. doi:10.1016/s0014-2999(98)00580-9. PMID 9809864.
  52. ^ George GARIBALDI, WO2023161533 (to Noema Pharma AG).
  53. ^ Jean-Michel Adam, et al. WO2013160273 (to F Hoffmann La Roche AG).
  54. ^ Pravin Iyer, et al. WO2008074703 (to Roche Palo Alto LLC).
  55. ^ a b Lucas, M. C., Weikert, R. J., Carter, D. S., Cai, H.-Y., Greenhouse, R., Iyer, P. S., Lin, C. J., Lee, E. K., Madera, A. M., Moore, A., Ozboya, K., Schoenfeld, R. C., Steiner, S., Zhai, Y., Lynch, S. M. (September 2010). "Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain". Bioorganic & Medicinal Chemistry Letters. 20 (18): 5559–5566. doi:10.1016/j.bmcl.2010.07.020.
  56. ^ "Noema Pharma". 18 June 2021.
  57. ^ "NOE-115 by Noema Pharma for Vasomotor Symptoms of Menopause (Hot Flashes): Likelihood of Approval". 19 June 2024.
  58. ^ "A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder". ClinicalTrials.gov. 2021-09-20.
  59. ^ "OPC 64005 — AdisInsight". adisinsight.springer.com. Retrieved 2022-12-19.
  60. ^ "Tesofensine — Saniona — AdisInsight". adisinsight.springer.com. Retrieved 2022-06-11.
  61. ^ Sramek, J. J.; Hardy, L. W.; Bieck, P.; Zamora, C.; Versavel, M.; Kharidia, J.; Grinnell, T.; Chen, Y.; Sullivan, M.; Ding, H.; Cutler, N. R. (May 2016). "Exploratory Biomarker Study of the Triple Reuptake Inhibitor SEP-432 Compared to the Dual Reuptake Inhibitor Duloxetine in Healthy Normal Subjects". CNS Neuroscience & Therapeutics. 22 (5): 404–412. doi:10.1111/cns.12513. PMC 6492792. PMID 26849844.
  62. ^ Liming Shao, et al. U.S. patent 9,868,718 (2018 to Sunovion Pharmaceuticals Inc).
  63. ^ Liming Shao, 11 More », WO2007081857 (2007 to Sepracor Inc.).
  64. ^ 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 (5): 481–90. doi:10.1021/jm00137a002. PMID 7241504.
  65. ^ 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 (17): 3885–8. doi:10.1021/ol061650w. PMID 16898842.
  66. ^ EP 0756596, Moldi, Peter; Watjen, Frank & Scheel-Krueger, Jorgen, "Tropane-2-aldoxine derivatives as neurotransmitter reuptake inhibitors", published 1997-02-05, assigned to Neurosearch AS 
  67. ^ 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.
  68. ^ Omer, LM (1982). "Pilot trials with diclofensine, a new psychoactive drug in depressed patients". International Journal of Clinical Pharmacology, Therapy, and Toxicology. 20 (7): 320–6. PMID 7107085.
  69. ^ 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 (12): 1360–7. doi:10.1177/0091270004269560. PMID 15545306. S2CID 26944976.
  70. ^ 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 (3): 444–452. doi:10.1016/j.pbb.2010.10.001. PMID 20934452. S2CID 20809504.
  71. ^ U.S. patent 3,308,160PHENYLBICYCLO[Z.Z.Z]OCTANE-L-AMINES AND SALTS THEREOF.
  72. ^ Fuller, R. W.; Snoddy, H. D.; Perry, K. W.; Bymaster, F. P.; Wong, D. T. (1978). "Studies on 4-(p-bromophenyl)-bicyclo (2,2,2) octan-1-amine as an inhibitor of uptake into serotonin neurones". Neuropharmacology 17 (10): 815–818. doi:10.1016/0028-3908(78)90069-2.
  73. ^ 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. 26 (5): 653–662. doi:10.1177/0269881111424931. PMID 22048884. S2CID 9365152.
  74. ^ "EUTHYMICS REPORTS TOP-LINE RESULTS FROM TRIADE TRIAL OF AMITIFADINE FOR MAJOR DEPRESSIVE DISORDER" (PDF) (Press release). Euthymics Bioscience, Inc. May 29, 2013. Archived from the original (PDF) on 2017-09-24. Retrieved 2022-06-11.
  75. ^ "Sunovion Discontinues Dasotraline Program". www.businesswire.com. 2020-05-13. Retrieved 2022-06-11.
  76. ^ a/s, H. Lundbeck (2010-09-28). "Efficacy and Safety of Lu AA34893 in Patients With Major Depressive Disorder". ClinicalTrials.gov.
  77. ^ "Development programme — Lundbeck". Archived from the original on 2011-09-29. Retrieved 2012-04-18.
  78. ^ "Search of: Lu AA24530 — List Results". ClinicalTrials.gov.
  79. ^ "Tedatioxetine — AdisInsight". adisinsight.springer.com. Retrieved 2022-06-11.
  80. ^ Wallach J, Brandt SD (2018). "Phencyclidine-Based New Psychoactive Substances". New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. pp. 261–303. doi:10.1007/164_2018_124. ISBN 978-3-030-10560-0. PMID 30105474.
  81. ^ 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 (4): 1420–32. doi:10.1021/jm050797a. PMC 2602954. PMID 16480278.
  82. ^ Alan Travis (2010-04-01). "NRG-1 may be next legal high to face ban by ministers | Politics". The Guardian. Retrieved 2010-04-03.
  83. ^ 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 (1): 18–38. Bibcode:2012NYASA1248...18C. doi:10.1111/j.1749-6632.2011.06199.x. PMID 22092008. S2CID 5108266.
  84. ^ 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 (1–3): 141–6. doi:10.1016/j.ejphar.2008.04.008. PMID 18499098.
  85. ^ Frazee, W. J.; Ohnmacht, C. J.; Malick, J. B. (1985). "Annual Reports in Medicinal Chemistry". Chapter 4. Antidepressants. Annual Reports in Medicinal Chemistry. Vol. 20. Elsevier. pp. 31–40. doi:10.1016/S0065-7743(08)61030-1. ISBN 978-0-12-040520-6.
  86. ^ Burkholder TP, Kudlacz EM, Tieu-Binh L, Knippenberg RW, Shatzer SA, Maynard GD, Webster ME, Horgan SW (April 1996). "Identification and chemical synthesis of MDL 105,212, a non-peptide tachykinin antagonist with high affinity for NK1 and NK2 receptors". Bioorganic & Medicinal Chemistry Letters. 6 (8): 951–6. doi:10.1016/0960-894X(96)00148-5.
  87. ^ Xavier Emonds-Alt, Patrick Gueule, Vincenzo Proietto, Didier Van Broeck, U.S. patent 5,679,693 (1997 to Sanofi SA).
  88. ^ Xavier Emonds-Alt, et al. U.S. patent 5,554,763 (1996 to Sanofi SA).
  89. ^ Carnmalm B, Rämsby S, Renyi AL, Ross SB, Ogren SO, Stjernstrom NE (1978). "Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants". Journal of Medicinal Chemistry. 21 (1): 78–82. doi:10.1021/jm00199a014. PMID 22757.
  90. ^ 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 (1–3): 73–9. doi:10.1016/j.ejphar.2008.05.008. PMID 18561912.
  91. ^ Sharma, Horrick; Santra, Soumava; Dutta, Aloke (2015). "Triple Reuptake Inhibitors as Potential Next-Generation Antidepressants: A New Hope?". Future Medicinal Chemistry. 7 (17): 2385–2406. doi:10.4155/fmc.15.134. PMC 4976848. PMID 26619226.
  92. ^ Chen, Zhengming; Skolnick, Phil (2007). "Triple uptake inhibitors: therapeutic potential in depression and beyond". Expert Opinion on Investigational Drugs. 16 (9): 1365–77. doi:10.1517/13543784.16.9.1365. ISSN 1354-3784. PMID 17714023.
  93. ^ Skolnick P, Basile AS (April 2007). "Triple reuptake inhibitors ("broad spectrum" antidepressants)". CNS Neurol Disord Drug Targets. 6 (2): 141–9. doi:10.2174/187152707780363285. PMID 17430151.
  94. ^ 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 (2): 712–5. doi:10.1021/jo102098y. PMID 21174473.
  95. ^ 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 (13): 4989–5001. doi:10.1021/jm100481d. PMID 20527970.
  96. ^ Bettati, Michela; Cavanni, Paolo; Di Fabio, Romano; Oliosi, Beatrice; Perini, Ornella; Scheid, Gunther; Tedesco, Giovanna; Zonzini, Laura; Micheli, Fabrizio (2010). "Oxa-azaspiro Derivatives: a Novel Class of Triple Re-uptake Inhibitors". ChemMedChem. 5 (3): 361–6. doi:10.1002/cmdc.200900482. ISSN 1860-7179. PMID 20112329.
  97. ^ Meyerson, Laurence R; Ong, Helen H; Martin, Lawrence L; Ellis, Daniel B (June 1980). "Effect of antidepressant agents on β-adrenergic receptor and neurotransmitter regulatory systems". Pharmacology Biochemistry and Behavior. 12 (6): 943–8. doi:10.1016/0091-3057(80)90457-8. PMID 6105676. S2CID 45400599.
  98. ^ Bøgesø KP, Christensen AV, Hyttel J, Liljefors (1985). "3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake". Journal of Medicinal Chemistry. 28 (12): 1817–28. doi:10.1021/jm00150a012. PMID 2999402.
  99. ^ Jan Kehler, Friedrich Kroll, & Karsten Juhl, WO2006007843 (to H Lundbeck AS).
  100. ^ Tamiz AP, Zhang J, Flippen-Anderson JL, Zhang M, Johnson KM, Deschaux O, Tella S, Kozikowski (2000). "Further SAR studies of piperidine-based analogues of cocaine. 2. Potent dopamine and serotonin reuptake inhibitors". Journal of Medicinal Chemistry. 43 (6): 1215–22. doi:10.1021/jm9905561. PMID 10737754.
  101. ^ WO 2005041875, Kozikowski, Alan P. & Zhou, Jia, "Dopamine-, norepinephrine- and serotonin- transporter- selective heterocyclic compounds and their therapeutic applications", published 2005-05-12, assigned to Georgetown University 
  102. ^ Axford, L.; Boot, J. R.; Hotten, T. M.; Keenan, M.; Martin, F. M.; Milutinovic, S.; Moore, N. A.; O'Neill, M. F.; Pullar, I. A.; Tupper, D. E.; Van Belle, K. R.; Vivien, V. (October 2003). "Bicyclo[2.2.1]heptanes as novel triple re-uptake inhibitors for the treatment of depression". Bioorganic & Medicinal Chemistry Letters. 13 (19): 3277–80. doi:10.1016/S0960-894X(03)00660-7. ISSN 0960-894X. PMID 12951108.
  103. ^ Christopher David Beadle, et al. WO2005000811 (to Eli Lilly and Co).
  104. ^ Clark, B. P.; Cases-Thomas, M. J.; Gallagher, P. T.; Gilmore, J.; Masters, J. J.; Timms, G. H.; Whatton, M. A.; Wood, M.Preparation of N,N-disubstituted 4-aminopiperidines as inhibitors of monoamine, in particular serotonin, norepinephrine, and dopamine reuptake. WO2004052858 (2004 to Eli Lilly and Co Ltd (GB)).
  105. ^ Boulet, S. L.; Clark, B. P.; Fairhurst, J.; Gallagher, P. T.; Johansson, A. M.; Whatton, M. A.; Wood, M. Preparation of 4-aminopiperidine derivatives as monoamine uptake inhibitors. WO2005092885 (2005 to Eli Lilly And Company).
  106. ^ 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 (1): 356–366. doi:10.1124/jpet.103.049825. PMID 12954808. S2CID 5654856.
  107. ^ Criado, Elisa (2 May 2014). "A fast-acting antidepressant could be on the horizon". The Independent. Retrieved 22 June 2014.
  108. ^ Talbot, Jeffery; Geffert, Laura; Wolters, Nicholas; Amos, Mary; Dallman, Elizabeth; Munro, Caitlin; Tolle, Erica; Larkey, Jessica; Tanda, Gianluigi; Katz, Jonathan; Indarte, Martin; Madura, Jeffry; Surratt, Christopher (April 2014). "A novel triple reuptake inhibitor with rapid antidepressant properties identified by virtual screening (1144.1)". The FASEB Journal. 28. Archived from the original on 2015-09-24. Retrieved 2014-06-23.
  109. ^ "A new fast-acting antidepressant (That's not ketamine) shows promise". Los Angeles Times. May 2014.
  110. ^ "Fast-acting antidepressant appears within reach".
  111. ^ Fang X, Guo L, Jia J, Jin GZ, Zhao B, Zheng YY, Li JQ, Zhang A, Zhen XC (2013). "SKF83959 is a novel triple reuptake inhibitor that elicits anti-depressant activity". Acta Pharmacologica Sinica. 34 (9): 1149–55. doi:10.1038/aps.2013.66. PMC 4003162. PMID 23892272.
  112. ^ Mondeshka, Diana; Angelova, Ivanka; Ivanov, Chavdar B.; Ivanova, Nedjalka S. (1990). "Racemische und optisch aktive 2-Chlorethylcarbamoyl-Derivate des 7,8-Dimethoxy-1-phenyl-1 H -3-benzazepins: Neue Strukturtypen von DA, NE und 5-HT Uptake Inhibitoren". Archiv der Pharmazie. 323 (10): 829–832. doi:10.1002/ardp.19903231003. ISSN 0365-6233. PMID 2150477.
  113. ^ 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. doi:10.1016/j.neuropharm.2013.04.060. ISSN 0028-3908. PMID 23748055. S2CID 6812669.
  114. ^ Hache, G.; Guiard, B.P.; Nguyen, T.H.; Quesseveur, G.; Gardier, A.M.; Peters, D.; Munro, G.; Coudoré, F. (2015). "Antinociceptive activity of the new triple reuptake inhibitor NS 18283 in a mouse model of chemotherapy-induced neuropathic pain". European Journal of Pain. 19 (3): 322–333. doi:10.1002/ejp.550. ISSN 1090-3801. PMID 25045036.
  115. ^ Birgitte L. Eriksen, et al. WO2008025777 (2008 to Neurosearch A/S).
  116. ^ Dan Peters, et al. U.S. patent 7,060,699 (2006 to NeuroSearch AS).
  117. ^ Peter Moldt, Jørgen SCHEEL-KRÜGER, Gunnar M. Olsen, Elsebet Østergaard NIELSEN , WO1997013770 (1997 to Neurosearch A/S).
  118. ^ Liming Shao, 12 More », WO2008151156 (to Sunovion Pharmaceuticals Inc.).
  119. ^ Shao, Liming; Hewitt, Michael C.; Wang, Fengjiang; Malcolm, Scott C.; Ma, Jianguo; Campbell, John E.; Campbell, Una C.; Engel, Sharon R.; Spicer, Nancy A.; Hardy, Larry W.; Schreiber, Rudy; Spear, Kerry L.; Varney, Mark A. (2011). "Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor". Bioorganic & Medicinal Chemistry Letters. 21 (5): 1438–41. doi:10.1016/j.bmcl.2011.01.016. PMID 21310609.
  120. ^ Shao L, Hewitt MC, Wang F, Malcolm SC, Ma J, Campbell JE, Campbell UC, Engel SR, Spicer NA, Hardy LW, Schreiber R, Spear KL, Varney MA (March 2011). "Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor". Bioorg Med Chem Lett. 21 (5): 1434–7. doi:10.1016/j.bmcl.2011.01.019. PMID 21310612.
  121. ^ Shao L, Li W, Xie Q, Yin H (February 2014). "Triple reuptake inhibitors: a patent review (2006–2012)". Expert Opin Ther Pat. 24 (2): 131–54. doi:10.1517/13543776.2014.859676. PMID 24289044.MID 24289044.
  122. ^ Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA (January 2011). "Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors". Bioorg Med Chem. 19 (1): 663–76. doi:10.1016/j.bmc.2010.10.034. PMID 21093273.
  123. ^ Liming Shao, et al. WO2007081542 (Sunovion Pharmaceuticals Inc).
  124. ^ Liming Shao & Jianguo Ma, WO2010091268 (Sunovion Pharmaceuticals Inc).
  125. ^ Heike Radeke & Liming Shao, US7812035 (2003 to Sunovion Pharmaceuticals Inc).
  126. ^ Liming Shao, et al. US8592608, US9133117 & US9850204 (2018 to Sunovion Pharmaceuticals Inc).
  127. ^ Ishichi, Yuji; Kimura, Eiji; Honda, Eiji; Yoshikawa, Masato; Nakahata, Takashi; Terao, Yasuko; Suzuki, Atsuko; Kawai, Takayuki; Arakawa, Yuuichi; Ohta, Hiroyuki; Kanzaki, Naoyuki; Nakagawa, Hideyuki; Terauchi, Jun (2013). "Novel triple reuptake inhibitors with low risk of CAD associated liabilities: Design, synthesis and biological activities of 4-[(1S)-1-(3,4-dichlorophenyl)-2-methoxyethyl]piperidine and related compounds". Bioorganic & Medicinal Chemistry. 21 (15): 4600–4613. doi:10.1016/j.bmc.2013.05.025.
  128. ^ Ishichi Yuji, Kimura Eiji & Terauchi Jun, WO2010016554 (to Takeda).
  129. ^ Kaur H, Izenwasser S, Verma A, Wade D, Housman A, Stevens ED, Mobley DL, Trudell ML (December 2009). "Synthesis and monoamine transporter affinity of 3alpha-arylmethoxy-3beta-arylnortropanes". Bioorg Med Chem Lett. 19 (24): 6865–8. doi:10.1016/j.bmcl.2009.10.087. PMC 2788963. PMID 19896846.
  130. ^ 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 (5): 411–441. doi:10.1016/0024-3205(95)00209-o. PMID 7623609.
  131. ^ U.S. patent 4,556,676
  132. ^ Li N, Li C, Han R, Wang Y, Yang M, Wang H, Tian J (2019). "LPM580098, a Novel Triple Reuptake Inhibitor of Serotonin, Noradrenaline, and Dopamine, Attenuates Neuropathic Pain". Front Pharmacol. 10 53. doi:10.3389/fphar.2019.00053. PMC 6382704. PMID 30837867.
  133. ^ Zhang F, Shao J, Tian J, Zhong Y, Ye L, Meng X, Liu Q, Wang H (April 2016). "Antidepressant-like Effects of LPM580153, A Novel Potent Triple Reuptake Inhibitor". Sci Rep. 6 24233. Bibcode:2016NatSR...624233Z. doi:10.1038/srep24233. PMC 4823741. PMID 27052887.
  134. ^ 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: 124–130. doi:10.1016/j.neuroscience.2011.08.064. PMID 21925241. S2CID 37122044.
  135. ^ Hou J, Xing Y, Zuo D, Wu Y, Tian J, Meng Q, Yang M (January 2015). "In vitro and in vivo characterization of PA01, a novel promising triple reuptake inhibitor". Physiol Behav. 138: 141–9. doi:10.1016/j.physbeh.2014.10.007. PMID 25447484.
  136. ^ Shaw AM, Boules M, Zhang Y, Williams K, Robinson J, Carlier PR, Richelson E (January 2007). "Antidepressant-like effects of novel triple reuptake inhibitors, PRC025 and PRC050". Eur J Pharmacol. 555 (1): 30–6. doi:10.1016/j.ejphar.2006.10.004. PMID 17109850.
  137. ^ Liu S, Zha C, Nacro K, Hu M, Cui W, Yang YL, Bhatt U, Sambandam A, Isherwood M, Yet L, Herr MT, Ebeltoft S, Hassler C, Fleming L, Pechulis AD, Payen-Fornicola A, Holman N, Milanowski D, Cotterill I, Mozhaev V, Khmelnitsky Y, Guzzo PR, Sargent BJ, Molino BF, Olson R, King D, Lelas S, Li YW, Johnson K, Molski T, Orie A, Ng A, Haskell R, Clarke W, Bertekap R, O'Connell J, Lodge N, Sinz M, Adams S, Zaczek R, Macor JE (July 2014). "Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors". ACS Med Chem Lett. 5 (7): 760–5. doi:10.1021/ml500053b. PMC 4094255. PMID 25050161.
  138. ^ Shuang Liu, Bruce F. Molino, Kassoum Nacro, WO2010132442 (2010 to Albany Molecular Research, Inc.). Page column 32.
  139. ^ Ki-Ho Lee, et al. WO2009148291 (to SK Biopharmaceuticals Co Ltd).
  140. ^ Chun-Eung Park, et al. WO2009148290 (to SK Biopharmaceuticals Co Ltd).
  141. ^ Lee KH, Park CE, Min KH, Shin YJ, Chung CM, Kim HH, Yoon HJ, Won-Kim, Ryu EJ, Shin YJ, Nam HS, Cho JW, Lee HY (September 2010). "Synthesis and pharmacological evaluation of 3-aryl-3-azolylpropan-1-amines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors". Bioorg Med Chem Lett. 20 (18): 5567–71. doi:10.1016/j.bmcl.2010.07.021. PMID 20724153.
  142. ^ Koprdova R, Csatlosova K, Durisova B, Bogi E, Majekova M, Dremencov E, Mach M (November 2019). "Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors". Molecules. 24 (23): 4218. doi:10.3390/molecules24234218. PMC 6930491. PMID 31757051.
  143. ^ Weng Z, Zheng Y, Li J (April 2015). "Synthesis, antidepressant activity, and toxicity of the erythro/threo racemates and optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl)hexan-1-ol". Chem Biol Drug Des. 85 (4): 454–60. doi:10.1111/cbdd.12438. PMID 25243904.
  144. ^ Weng Z, Li J. Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056). Bioorg Med Chem Lett. 2010 Feb 1;20(3):1256-9. doi: 10.1016/j.bmcl.2009.11.108. Epub 2009 Nov 27. PMID 20022503.
  145. ^ Honda E, Ishichi Y, Kimura E, Yoshikawa M, Kanzaki N, Nakagawa H, Terao Y, Suzuki A, Kawai T, Arakawa Y, Ohta H, Terauchi J (August 2014). "Design, synthesis, and biological activities of 1-aryl-1,4-diazepan-2-one derivatives as novel triple reuptake inhibitors". Bioorg Med Chem Lett. 24 (16): 3898–902. doi:10.1016/j.bmcl.2014.06.046. PMID 25017029.
  146. ^ Paudel S, Acharya S, Yoon G, Kim KM, Cheon SH (April 2017). "Design, synthesis and in vitro activity of 1,4-disubstituted piperazines and piperidines as triple reuptake inhibitors". Bioorg Med Chem. 25 (7): 2266–76. doi:10.1016/j.bmc.2017.02.051. PMID 28274674.
  147. ^ Paudel S, Min X, Acharya S, Khadka DB, Yoon G, Kim KM, Cheon SH (October 2017). "Triple reuptake inhibitors: Design, synthesis and structure-activity relationship of benzylpiperidine-tetrazoles". Bioorg Med Chem. 25 (20): 5278–89. doi:10.1016/j.bmc.2017.07.046. PMID 28807575.
  148. ^ Paudel S, Wang S, Kim E, Kundu D, Min X, Shin CY, Kim KM. Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors. Biomol Ther (Seoul). 2021 Nov 18. doi: 10.4062/biomolther.2021.119. Epub ahead of print. PMID 34789584.
  149. ^ Han M, Song C, Jeong N, Hahn HG (September 2014). "Exploration of 3-Aminoazetidines as Triple Reuptake Inhibitors by Bioisosteric Modification of 3-α-Oxyazetidine". ACS Med Chem Lett. 5 (9): 999–1004. doi:10.1021/ml500187a. PMC 4160755. PMID 25221656.
  150. ^ Yun J, Han M, Song C, Cheon SH, Choi K, Hahn HG (August 2014). "Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors". Bioorg Med Chem Lett. 24 (15): 3234–7. doi:10.1016/j.bmcl.2014.06.026. PMID 24974340.
  151. ^ Mondeshka DM, Angelova IG, Tancheva CN, Ivanov CB, Daleva LD, Ivanova NS (1994). "Synthesis, antiulcer and antidepressive activity of 4-(4-halophenyl)-2-phenyl-1,2,3,4-tetrahydroisoquinolines". Farmaco. 49 (7–8): 475–80. PMID 7945712.
  152. ^ CA2015114 idem Donka M. Mondeshka, 10 More », EP0400319 (1990 to N I S Pri Vchti).
  153. ^ James P. Beck, Mark A. Smith, Matt A. Curry, M. A. Aryl- and heteroarylsubstituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin. WO2001032625 (2001 to Du Pont Pharmaceuticals Company).
  154. ^ Zheng YY, Guo L, Zhen XC, Li JQ (August 2012). "Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors". Eur J Med Chem. 54: 123–36. doi:10.1016/j.ejmech.2012.04.030. PMID 22608762.
  155. ^ Han Y, Han M, Shin D, Song C, Hahn HG (September 2012). "Exploration of novel 3-substituted azetidine derivatives as triple reuptake inhibitors". J Med Chem. 55 (18): 8188–92. doi:10.1021/jm3008294. PMID 22938049.
  156. ^ Roggen H, Kehler J, Stensbøl TB, Hansen T (May 2007). "Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters". Bioorg Med Chem Lett. 17 (10): 2834–7. doi:10.1016/j.bmcl.2007.02.054. PMID 17350257.
  157. ^ Mondeshka, Diana; Angelova, Ivanka; Ivanov, Chavdar B.; Ivanova, Nedjalka S. (1990). "Racemische und optisch aktive 2-Chlorethylcarbamoyl-Derivate des 7,8-Dimethoxy-1-phenyl-1H-3-benzazepins: Neue Strukturtypen von DA, NE und 5-HT Uptake Inhibitoren". Archiv der Pharmazie. 323 (10): 829–832. doi:10.1002/ardp.19903231003.
  158. ^ Fang, Xing; Guo, Lin; Jia, Jia; Jin, Guo-zhang; Zhao, Bin; Zheng, Yong-yong; Li, Jian-qi; Zhang, Ao; Zhen, Xue-chu (2013). "SKF83959 is a novel triple reuptake inhibitor that elicits anti-depressant activity". Acta Pharmacologica Sinica. 34 (9): 1149–1155. doi:10.1038/aps.2013.66.
  159. ^ Bannwart, L. M., Carter, D. S., Cai, H.-Y., Choy, J. C., Greenhouse, R., Jaime-Figueroa, S., Iyer, P. S., Lin, C. J., Lee, E. K., Lucas, M. C., Lynch, S. M., Madera, A. M., Moore, A., Ozboya, K., Raptova, L., Roetz, R., Schoenfeld, R. C., Stein, K. A., Steiner, S., Villa, M., Weikert, R. J., Zhai, Y. (December 2008). "Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors". Bioorganic & Medicinal Chemistry Letters. 18 (23): 6062–6066. doi:10.1016/j.bmcl.2008.10.025.
  160. ^ Matthew C. Lucas, Ryan Craig Schoenfeld, Robert James Weikert, WO2009115427 (2011 to Hoffmann-La Roche Inc).
  161. ^ Ryan Craig Schoenfeld, WO2011067273 (2011 to F. Hoffmann-La Roche Ag).
  162. ^ Lucas, M. C., Carter, D. S., Cai, H.-Y., Lee, E. K., Schoenfeld, R. C., Steiner, S., Villa, M., Weikert, R. J., Iyer, P. S. (August 2009). "Novel, achiral aminoheterocycles as selective monoamine reuptake inhibitors". Bioorganic & Medicinal Chemistry Letters. 19 (16): 4630–4633. doi:10.1016/j.bmcl.2009.06.076.
  163. ^ Carter, D. S., Cai, H.-Y., Lee, E. K., Iyer, P. S., Lucas, M. C., Roetz, R., Schoenfeld, R. C., Weikert, R. J. (July 2010). "2-Substituted N-aryl piperazines as novel triple reuptake inhibitors for the treatment of depression". Bioorganic & Medicinal Chemistry Letters. 20 (13): 3941–3945. doi:10.1016/j.bmcl.2010.05.008.
  164. ^ Pettersson, E. (August 1995). "Studies of four novel diphenylbutylpiperazinepyridyl derivatives on release and inhibition of reuptake of dopamine, serotonin and noradrenaline by rat brain in vitro". European Journal of Pharmacology. 282 (1–3): 131–135. doi:10.1016/0014-2999(95)00300-A. PMID 7498267.
  165. ^ Vejdělek, Z.; Metyš, J.; Holubek, J.; Svátek, E.; Protiva, M. (1984). "Potential antiparkinsonic agents: Synthesis and pharmacology of some 4-fluoro-4'-halogen'benzhydryl 2-(N,N-disubstituted amino)ethyl ethers". Collection of Czechoslovak Chemical Communications. 49 (11): 2649–2660. doi:10.1135/cccc19842649.
  166. ^ Zee P. van der, Hespe W.: 5th Int. Symp. Med. Chem., Paris, July 1976; Abstr. p. 52 (No 053).
  167. ^ Rothman, R. B.; Ananthan, S.; Partilla, J. S.; Saini, S. K.; Moukha-Chafiq, O.; Pathak, V.; Baumann, M. H. (June 2015). "Studies of the Biogenic Amine Transporters 15. Identification of Novel Allosteric Dopamine Transporter Ligands with Nanomolar Potency". The Journal of Pharmacology and Experimental Therapeutics. 353 (3): 529–538. doi:10.1124/jpet.114.222299. PMID 25788711.
  168. ^ Subramaniam Ananthan & Richard B. Rothman, WO2016090296 (to Southern Research Institute, US Department of Health and Human Services).
  169. ^ 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 (1): 68–73. doi:10.1016/j.phrs.2009.02.012. PMID 19427589.
  170. ^ Stein, A. C.; Viana, A. F.; Müller, L. G.; Nunes, J. M.; Stolz, E. D.; Do Rego, J. C.; Costentin, J; von Poser, G. L.; Rates, S. M. (2012). "Uliginosin B, a phloroglucinol derivative from Hypericum polyanthemum: A promising new molecular pattern for the development of antidepressant drugs". Behavioural Brain Research. 228 (1): 66–73. doi:10.1016/j.bbr.2011.11.031. PMID 22155486. S2CID 1518033.
  171. ^ US 2011313034, Rates, Stela Maris Kuze; Von Poser, Gilsane Lino & Viana, Alice Fialho et al., "Neuroactive plant extract from Hypericum polyanthemum", published 2011-12-22, assigned to Universidade Federal Do Rio Grande Do Sul and Universite de Rouen 
  172. ^ Mechan, Annis O.; Fowler, Ann; Seifert, Nicole; Rieger, Henry; Wöhrle, Tina; Etheve, Stéphane; Wyss, Adrian; Schüler, Göde; Colletto, Biagio; Kilpert, Claus; Aston, James; Elliott, J. Martin; Goralczyk, Regina; Mohajeri, M. Hasan (2010). "Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract". British Journal of Nutrition. 105 (8): 1150–63. doi:10.1017/S0007114510004940. ISSN 0007-1145. PMID 21205415.
  173. ^ 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. doi:10.1016/j.bbr.2012.10.010. ISSN 0166-4328. PMID 23085339. S2CID 31553844.
  174. ^ 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 (3): 431–9. doi:10.1016/j.pbb.2011.10.001. ISSN 0091-3057. PMID 22005599. S2CID 207331897.
  175. ^ Jin, Zeng-liang; Gao, Nana; Zhang, Jian-rui; Li, Xiao-rong; Chen, Hong-xia; Xiong, Jie; Li, Yun-feng; Tang, Yu (2014). "The discovery of Yuanzhi-1, a triterpenoid saponin derived from the traditional Chinese medicine, has antidepressant-like activity". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 53: 9–14. doi:10.1016/j.pnpbp.2014.02.013.
  176. ^ Jin, Zeng-liang; Gao, Nana; Li, Xiao-rong; Tang, Yu; Xiong, Jie; Chen, Hong-xia; Xue, Rui; Li, Yun-Feng (2015). "The antidepressant-like pharmacological profile of Yuanzhi-1, a novel serotonin, norepinephrine and dopamine reuptake inhibitor". European Neuropsychopharmacology. 25 (4): 544–556. doi:10.1016/j.euroneuro.2015.01.005.
[edit]
  • Wikimedia Commons logo Media related to Serotonin–norepinephrine–dopamine reuptake inhibitors at Wikimedia Commons
Retrieved from "https://en.wikipedia.org/w/index.php?title=Serotonin–norepinephrine–dopamine_reuptake_inhibitor&oldid=1361576645"