Inhibitor preuzimanja serotonin-norepinefrin-dopamina — разлика између измена

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Верзија на датум 30. децембар 2023. у 21:34

Inhibitor preuzimanja serotonin-norepinefrin-dopamina (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. The naturally-occurring and potent SNDRI cocaine is widely used recreationally and often illegally for the euphoric effects it produces.

Other SNDRIs were developed as potential antidepressants and treatments for other disorders, such as obesity, cocaine addiction, attention-deficit hyperactivity disorder (ADHD), and chronic pain. They are an extension of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) whereby the addition of dopaminergic action is thought to have the possibility of heightening therapeutic benefit. However, increased side effects and abuse potential are potential concerns of these agents relative to their SSRI and SNRI counterparts.

The SNDRIs are similar to non-selective monoamine oxidase inhibitors (MAOIs) such as phenelzine and tranylcypromine in that they increase the action of all three of the major monoamine neurotransmitters. They are also similar to serotonin–norepinephrine–dopamine releasing agents (SNDRAs) like MDMA ("ecstasy") and α-ethyltryptamine (αET) for the same reason, although they act via a different mechanism and have differing physiological and qualitative effects.

Although their primary mechanisms of action are as NMDA receptor antagonists, ketamine and phencyclidine are also SNDRIs and are similarly encountered as drugs of abuse.

Indikacije

Depresija

Teža depresijska epizoda (engl. Major depressive disorder, MDD) is the foremost reason supporting the need for development of an SNDRI.[1][2][3][4][5][6][7][8][9][10] According to the World Health Organization, depression is the leading cause of disability and the 4th leading contributor to the global burden of disease in 2000. By the year 2020, depression is projected to reach 2nd place in the ranking of DALYs.[11]

About 16% of the population is estimated to be affected by major depression, and another 1% is affected by bipolar disorder, one or more times throughout an individual's lifetime. The presence of the common symptoms of these disorders are collectively called 'depressive syndrome' and includes a long-lasting depressed mood, feelings of guilt, anxiety, and recurrent thoughts of death and suicide.[12] Other symptoms including poor concentration, a disturbance of sleep rhythms (insomnia or hypersomnia), and severe fatigue may also occur. Individual patients present differing subsets of symptoms, which may change over the course of the disease highlighting its multifaceted and heterogeneous nature.[6] Depression is often highly comorbid with other diseases, e.g. cardiovascular disease (myocardial infarction,[13] stroke),[14] diabetes,[15] cancer,[16] Depressed subjects are prone to smoking,[17] substance abuse,[18] eating disorders, obesity, high blood pressure, pathological gambling and internet addiction,[19] and on average have a 15 to 30 year shorter lifetime compared with the general population.[14]

Reference

  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 (1): 53—77. PMC 5084256 Слободан приступ. 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 (6): 767—88. PMID 19426122. S2CID 71382550. 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 (11): 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 (4): 338—43. PMC 2701280 Слободан приступ. PMID 19587855. doi:10.2174/157015908787386078. 
  5. ^ Chen, Z; Skolnick, P (2007). „Triple uptake inhibitors: Therapeutic potential in depression and beyond”. Expert Opinion on Investigational Drugs. 16 (9): 1365—77. PMID 17714023. S2CID 20271918. doi:10.1517/13543784.16.9.1365. 
  6. ^ а б 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 (2): 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 (5–6): 566—74. PMC 2644662 Слободан приступ. 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 (3): 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 2938284 Слободан приступ. PMID 20856599. doi:10.2147/ndt.s10485 Слободан приступ. 
  10. ^ Rakofsky, JJ; Holtzheimer, PE; Nemeroff, CB (2009). „Emerging targets for antidepressant therapies”. Current Opinion in Chemical Biology. 13 (3): 291—302. PMC 4410714 Слободан приступ. PMID 19501541. doi:10.1016/j.cbpa.2009.04.617. 
  11. ^ „Depression”. World Health Organization. WHO. Архивирано из оригинала 2010-07-17. г. 
  12. ^ Lee, S; Jeong, J; Kwak, Y; Park, SK (2010). „Depression research: Where are we now?”. Molecular Brain. 3: 8. PMC 2848031 Слободан приступ. PMID 20219105. doi:10.1186/1756-6606-3-8 Слободан приступ. 
  13. ^ Larsen, KK; Vestergaard, M; Søndergaard, J; Christensen, B (2012). „Screening for depression in patients with myocardial infarction by general practitioners”. European Journal of Preventive Cardiology. 20 (5): 800—806. PMID 22496274. S2CID 24986156. doi:10.1177/2047487312444994 Слободан приступ. 
  14. ^ а б Saravane, D; Feve, B; Frances, Y; Corruble, E; Lancon, C; Chanson, P; Maison, P; Terra, JL; et al. (2009). „Drawing up guidelines for the attendance of physical health of patients with severe mental illness”. L'Encéphale. 35 (4): 330—9. PMID 19748369. doi:10.1016/j.encep.2008.10.014. 
  15. ^ Rustad, JK; Musselman, DL; Nemeroff, CB (2011). „The relationship of depression and diabetes: Pathophysiological and treatment implications”. Psychoneuroendocrinology. 36 (9): 1276—86. PMID 21474250. S2CID 32439196. doi:10.1016/j.psyneuen.2011.03.005. 
  16. ^ Li, M; Fitzgerald, P; Rodin, G (2012). „Evidence-based treatment of depression in patients with cancer”. Journal of Clinical Oncology. 30 (11): 1187—96. PMID 22412144. doi:10.1200/JCO.2011.39.7372. 
  17. ^ Tsuang, MT; Francis, T; Minor, K; Thomas, A; Stone, WS (2012). „Genetics of smoking and depression”. Human Genetics. 131 (6): 905—15. PMID 22526528. S2CID 11532256. doi:10.1007/s00439-012-1170-6. 
  18. ^ Davis, LL; Wisniewski, SR; Howland, RH; Trivedi, MH; Husain, MM; Fava, M; McGrath, PJ; Balasubramani, GK; et al. (2010). „Does comorbid substance use disorder impair recovery from major depression with SSRI treatment? An analysis of the STAR*D level one treatment outcomes”. Drug and Alcohol Dependence. 107 (2–3): 161—70. PMID 19945804. doi:10.1016/j.drugalcdep.2009.10.003. 
  19. ^ Barrault, S; Varescon, I (2012). „Psychopathology in online pathological gamblers: A preliminary study”. L'Encéphale. 38 (2): 156—63. PMID 22516274. doi:10.1016/j.encep.2011.01.009. 

Spoljašnje veze

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