neurotransmitter uptake inhibitors


Summary: Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.

Top Publications

  1. Overstreet L, Jones M, Westbrook G. Slow desensitization regulates the availability of synaptic GABA(A) receptors. J Neurosci. 2000;20:7914-21 pubmed
    ..Accumulation of channels in this absorbing state allows GABA(A) receptors to detect even a few molecules of GABA in the synaptic cleft. ..
  2. Rothman R, Baumann M, Dersch C, Romero D, Rice K, Carroll F, et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001;39:32-41 pubmed
    ..These results suggest that NE may contribute to the amphetamine-type subjective effects of stimulants in humans. ..
  3. Hauser R, Salin L, Juhel N, Konyago V. Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease. Mov Disord. 2007;22:359-65 pubmed
  4. Lengyel K, Pieschl R, Strong T, Molski T, Mattson G, Lodge N, et al. Ex vivo assessment of binding site occupancy of monoamine reuptake inhibitors: methodology and biological significance. Neuropharmacology. 2008;55:63-70 pubmed publisher
    ..The biological relevance of the monoamine transporter occupancy for these compounds is discussed. ..
  5. Prins J, Westphal K, Korte Bouws G, Quinton M, Schreiber R, Olivier B, et al. 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. Pharmacol Biochem Behav. 2011;97:444-52 pubmed publisher
    ..This seems to indicate that this putative antidepressant drug has no lasting antidepressant-like behavioral effects in the absence of the drug in the brain...
  6. Skolnick P, Popik P, Janowsky A, Beer B, Lippa A. "Broad spectrum" antidepressants: is more better for the treatment of depression?. Life Sci. 2003;73:3175-9 pubmed
  7. Keros S, Hablitz J. Subtype-specific GABA transporter antagonists synergistically modulate phasic and tonic GABAA conductances in rat neocortex. J Neurophysiol. 2005;94:2073-85 pubmed
    ..Thus neocortical GAT-1 and GAT-2/3 have distinct but overlapping roles in modulating GABA conductances. ..
  8. Rascol O, Poewe W, Lees A, Aristin M, Salin L, Juhel N, et al. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch Neurol. 2008;65:577-83 pubmed publisher
    ..To assess the safety and efficacy of tesofensine, a triple monoamine reuptake inhibitor, in patients with advanced Parkinson disease (PD)...
  9. Sindrup S, Otto M, Finnerup N, Jensen T. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005;96:399-409 pubmed
    ..However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain. ..

More Information

Publications114 found, 100 shown here

  1. Shaw A, Boules M, Zhang Y, Williams K, Robinson J, Carlier P, et al. Antidepressant-like effects of novel triple reuptake inhibitors, PRC025 and PRC050. Eur J Pharmacol. 2007;555:30-6 pubmed
    ..Therefore it appears that our compounds may possess antidepressant activity and represent a new class of triple reuptake inhibitors. ..
  2. Massey P, Johnson B, Moult P, Auberson Y, Brown M, Molnar E, et al. Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci. 2004;24:7821-8 pubmed
    ..Therefore, NMDARs with different synaptic locations and subunit compositions are involved in various forms of synaptic plasticity in adult cortex. ..
  3. Wyrwich K, Spratt D, Gass M, Yu H, Bobula J. Identifying meaningful differences in vasomotor symptoms among menopausal women. Menopause. 2008;15:698-705 pubmed publisher
    ..64 fewer moderate to severe hot flushes per day and 0.42 fewer nighttime awakenings per night. A dose of 100 mg DVS met both of these important vasomotor symptom change thresholds. ..
  4. Wenge B, Bonisch H. Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters. Naunyn Schmiedebergs Arch Pharmacol. 2009;380:523-9 pubmed publisher
    ..Thus, DSP4's high-affinity uptake through the NAT together with its completely irreversible mode of interaction with the NAT may contribute to its selectivity as noradrenergic neurotoxin. ..
  5. Nichols A, Abell M, Madelyn A, Chen Y, Behrle J, Frick G, et al. Effects of desvenlafaxine on the pharmacokinetics of desipramine in healthy adults. Int Clin Psychopharmacol. 2013;28:99-105 pubmed publisher
    ..These results indicate that desvenlafaxine is a relatively weak inhibitor of CYP2D6 and that desvenlafaxine 100 mg, twice the recommended therapeutic dose of 50 mg, is unlikely to cause drug-drug interactions with CYP2D6 substrates. ..
  6. Proietto J, Fam B, Ainslie D, Thorburn A. Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000;9:1317-26 pubmed
    ..As some redundancy exists in the central regulatory system controlling body weight, some agents might need to be used in combination to be effective. ..
  7. Sha L, Miller S, Szurszewski J. Electrophysiological effects of GABA on cat pancreatic neurons. Am J Physiol Gastrointest Liver Physiol. 2001;280:G324-31 pubmed
    ..The data suggest that endogenous GABA released from ganglionic glial cells acts on pancreatic ganglion neurons through GABA(A) receptors. ..
  8. Hentschel S, Lewerenz A, Nieber K. Activation of A(3) receptors by endogenous adenosine inhibits synaptic transmission during hypoxia in rat cortical neurons. Restor Neurol Neurosci. 2003;21:55-63 pubmed
    ..We conclude that a high level of endogenous adenosine, which occurs during hypoxia, activates A(3) receptors. Their activation contributes to PSP inhibition by adenosine during hypoxia. ..
  9. Rao T, Lariosa Willingham K, Yu N. Glutamate-dependent glutamine, aspartate and serine release from rat cortical glial cell cultures. Brain Res. 2003;978:213-22 pubmed
    ..These results further substantiate coupling between glutamate and glutamine, and shed light on glutamate-dependent release of serine and aspartate, which may further contribute to excitatory neurotransmission. ..
  10. Prins J, Kenny P, Doomernik I, Schreiber R, Olivier B, Mechiel Korte S. The triple reuptake inhibitor DOV 216,303 induces long-lasting enhancement of brain reward activity as measured by intracranial self-stimulation in rats. Eur J Pharmacol. 2012;693:51-6 pubmed publisher
    ..Elevated ICSS thresholds were found after amphetamine administration, which is consistent with previously reported reward deficits induced after amphetamine-withdrawal...
  11. Fisar Z, Fuksová K, Sikora J, Kališová L, Velenovská M, Novotná M. Distribution of antidepressants between plasma and red blood cells. Neuro Endocrinol Lett. 2006;27:307-13 pubmed
    ..This ratio is to a large extent characteristic of a particular antidepressant. ..
  12. Hirota K, Sasaki R, Roth S, Yamazaki M. Presynaptic actions of general anesthetics are responsible for frequency-dependent modification of synaptic transmission in the rat hippocampal CA1. Anesth Analg. 2010;110:1607-13 pubmed publisher
    ..The stimulus frequency-dependent modification of synaptic transmission might be responsible for the unsuccessful immobilization or hypnosis during general anesthesia after IV anesthetic administration. ..
  13. Gallagher J, Strzinek R, Cheng R, Ausmanas M, Astl D, Seljan P. The effect of dose titration and dose tapering on the tolerability of desvenlafaxine in women with vasomotor symptoms associated with menopause. J Womens Health (Larchmt). 2012;21:188-98 pubmed publisher
    ..Taper regimens of desvenlafaxine 50 mg/d-placebo or 50/25-mg/d, were better tolerated than abrupt discontinuation or desvenlafaxine 50 mg given every other day taper regimen. ..
  14. Segovia G, Mora F. Involvement of NMDA and AMPA/kainate receptors in the effects of endogenous glutamate on extracellular concentrations of dopamine and GABA in the nucleus accumbens of the awake rat. Brain Res Bull. 2001;54:153-7 pubmed
    ..These results suggest a differential mediation of ionotropic glutamatergic receptors in the actions of endogenous glutamate on extracellular concentration of dopamine and GABA. ..
  15. Hainsworth A, Spadoni F, Lavaroni F, Bernardi G, Stefani A. Effects of extracellular pH on the interaction of sipatrigine and lamotrigine with high-voltage-activated (HVA) calcium channels in dissociated neurones of rat cortex. Neuropharmacology. 2001;40:784-91 pubmed
    ..6 and with the channel activation process, and differs from that for lamotrigine. ..
  16. Oben J, Diehl A. Sympathetic nervous system regulation of liver repair. Anat Rec A Discov Mol Cell Evol Biol. 2004;280:874-83 pubmed
    ..Given evidence that the SNS regulates the viability and activation of HSCs and OCs differentially, SNSIs may be novel therapies to improve the repair of damaged livers. ..
  17. Weikop P, Yoshitake T, Kehr J. Differential effects of adjunctive methylphenidate and citalopram on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain. Eur Neuropsychopharmacol. 2007;17:658-71 pubmed
  18. Dunlop J, Eliasof S, Stack G, McIlvain H, Greenfield A, Kowal D, et al. WAY-855 (3-amino-tricyclo[]heptane-1,3-dicarboxylic acid): a novel, EAAT2-preferring, nonsubstrate inhibitor of high-affinity glutamate uptake. Br J Pharmacol. 2003;140:839-46 pubmed
    ..WAY-855 represents a novel structure in glutamate transporter pharmacology, and exploration of this structure might provide insights into the discrimination between EAAT2 and other EAAT subtypes. ..
  19. Botts S. Moving beyond balance for a better antidepressant. Am J Health Syst Pharm. 2005;62:2479 pubmed
  20. Holman A. Pragmatic consideration of recent randomized, placebo-controlled clinical trials for treatment of fibromyalgia. Curr Pain Headache Rep. 2008;12:393-8 pubmed
    ..Studies with gabapentin, pregabalin, duloxetine, milnacipran, sodium oxybate, and pramipexole for treatment of FM are discussed. ..
  21. Binz T. Clostridial neurotoxin light chains: devices for SNARE cleavage mediated blockade of neurotransmission. Curr Top Microbiol Immunol. 2013;364:139-57 pubmed publisher
    ..SNARE cleavage causes the blockade of neurotransmitter release. This chapter details the molecular basis for the highly selective substrate recognition and cleavage mechanism of CNT. ..
  22. Tejeda H, Counotte D, Oh E, Ramamoorthy S, Schultz Kuszak K, Bäckman C, et al. Prefrontal cortical kappa-opioid receptor modulation of local neurotransmission and conditioned place aversion. Neuropsychopharmacology. 2013;38:1770-9 pubmed publisher
    ..These findings demonstrate that mPFC KORs negatively regulate DA and amino-acid neurotransmission, and are necessary for KOR-mediated aversion. ..
  23. Mao J, Sung B, Ji R, Lim G. Neuronal apoptosis associated with morphine tolerance: evidence for an opioid-induced neurotoxic mechanism. J Neurosci. 2002;22:7650-61 pubmed
    ..These results indicate an opioid-induced neurotoxic consequence regulated by the NMDAR-caspase pathway, a mechanism that may have clinical implications in opioid therapy and substance abuse. ..
  24. Anttila S, Leinonen E. Duloxetine Eli Lilly. Curr Opin Investig Drugs. 2002;3:1217-21 pubmed
    ..At the same time, Credit Suisse First Boston anticipated launch for late 2002, with US $220 million in duloxetine revenues in 2003 and US $457 million in 2004 [450936]. ..
  25. de Yebra L, Malpesa Y, Ursu G, Pugliese M, Liévens J, Kerkerian Le Goff L, et al. Dissociation between hippocampal neuronal loss, astroglial and microglial reactivity after pharmacologically induced reverse glutamate transport. Neurochem Int. 2006;49:691-7 pubmed
    ..These data suggest a specific response of microglia to PDC whose neuronal effects may differ with the infused dose. ..
  26. Vélez Fort M, Maldonado P, Butt A, Audinat E, Angulo M. Postnatal switch from synaptic to extrasynaptic transmission between interneurons and NG2 cells. J Neurosci. 2010;30:6921-9 pubmed publisher
    ..Hence, after development is complete, volume transmission allows NG2 cells to integrate neuronal activity patterns at frequencies occurring during in vivo sensory stimulation. ..
  27. Jin Z, Gao N, Zhou D, Chi M, Yang X, Xu J. The extracts of Fructus Akebiae, a preparation containing 90% of the active ingredient hederagenin: serotonin, norepinephrine and dopamine reuptake inhibitor. Pharmacol Biochem Behav. 2012;100:431-9 pubmed publisher
    ..Taken together, our current study showed for the first time that FAE is a novel triple inhibitor of monoamine transporters, which may be one the mechanisms of its antidepressant activity. ..
  28. Bymaster F, Chao P, Schulze H, Tran P, Marshall R. Biopharmaceutical characterization, metabolism, and brain penetration of the triple reuptake inhibitor amitifadine. Drug Metab Lett. 2013;7:23-33 pubmed
    ..Overall, these studies suggest that amitifadine has drug-like characteristics favorable for drug development. ..
  29. Waddell A, Holtzman S. Modulation of cocaine-induced motor activity in the rat by opioid receptor agonists. Behav Pharmacol. 1998;9:397-407 pubmed
    ..The synergistic effect seen with delta-opioid receptor activation may involve a mu-opioid receptor component, and is probably mediated via a dopaminergic pathway. ..
  30. Himi T, Ikeda M, Yasuhara T, Murota S. Oxidative neuronal death caused by glutamate uptake inhibition in cultured hippocampal neurons. J Neurosci Res. 2003;71:679-88 pubmed
  31. Hofner G, Wanner K. Evaluation of GABA uptake in subcellular fractions of bovine frontal cortex and brainstem. Neurosci Lett. 2004;364:53-7 pubmed
  32. Heffernan G, Coghlan R, Manas E, McDevitt R, Li Y, Mahaney P, et al. Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles. Bioorg Med Chem. 2009;17:7802-15 pubmed publisher
    ..The synthesis and structure-activity relationship (SAR) of this novel series of compounds is also presented. ..
  33. Einat H, Clenet F, Shaldubina A, Belmaker R, Bourin M. The antidepressant activity of inositol in the forced swim test involves 5-HT(2) receptors. Behav Brain Res. 2001;118:77-83 pubmed
    ..The present data indicates that the antidepressant effect of inositol may involve 5-HT(2) receptors. It is thus possible that the effects of reuptake antidepressant drugs and the effects of inositol may have a common final pathway. ..
  34. Noji T, Nan ya K, Mizutani M, Katagiri C, Sano J, Takada C, et al. KF24345, an adenosine uptake inhibitor, ameliorates the severity and mortality of lethal acute pancreatitis via endogenous adenosine in mice. Eur J Pharmacol. 2002;454:85-93 pubmed
    ..These results suggest that KF24345 shows anti-pancreatitis effects via endogenous adenosine and adenosine A(2A) receptors. The adenosine uptake inhibition could be a new therapeutic approach for acute pancreatitis. ..
  35. Hayase T, Yamamoto Y, Yamamoto K. Brain excitatory amino acid transporters (EAATs) and treatment of methamphetamine toxicity. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2003;38:498-511 pubmed
  36. Hibi H, Ohori T, Yamada Y. DPP-IV inhibitor may affect spermatogenesis. Diabetes Res Clin Pract. 2011;93:e74-5 pubmed publisher
    ..This treatment was effective; he could ejaculate. He began receiving DPP-IV inhibitor (Sitagliptin 50 mg, daily), in lieu of insulin injection. Unusual effect on semen quality was occurred following the administration of the drug. ..
  37. Zhang P, Terefenko E, McComas C, Mahaney P, Vu A, Trybulski E, et al. Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett. 2008;18:6067-70 pubmed publisher
    ..Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5). ..
  38. Kovacs I, Skuban N, Nyitrai G, Kardos J. Inhibition of [3H]D-aspartate release by deramciclane. Eur J Pharmacol. 1999;381:121-7 pubmed
    ..These results suggest a role for presynaptic inhibition of excitatory amino acid release and GABA uptake in the anxiolytic properties of deramciclane. ..
  39. Reis M, Aamo T, Spigset O, Ahlner J. Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database. Ther Drug Monit. 2009;31:42-56 pubmed publisher
    ..By presenting a comprehensive compilation of therapeutic drug monitoring data for each drug, a reference tool is created, in addition to improved pharmacokinetic knowledge of antidepressant drugs. ..
  40. Gahring L, Vasquez Opazo G, Rogers S. Choline promotes nicotinic receptor alpha4 + beta2 up-regulation. J Biol Chem. 2010;285:19793-801 pubmed publisher
    ..These findings extend the view that up-regulation of alpha4 + beta2 nAChRs is a normal physiological response to altered metabolic and inflammatory conditions...
  41. Prickaerts J, De Vry J, Boere J, Kenis G, Quinton M, Engel S, et al. Differential BDNF responses of triple versus dual reuptake inhibition in neuronal and astrocytoma cells as well as in rat hippocampus and prefrontal cortex. J Mol Neurosci. 2012;48:167-75 pubmed publisher
  42. Gazulla J, Benavente I, Sarasa Barrio M. [Adult-onset ataxia-telangiectasia. A clinical and therapeutic observation]. Neurologia. 2006;21:447-51 pubmed
    ..A synergistic effect with pregabalin is proposed as the cause of the improvement obtained with the addition of tiagabine...
  43. Zhang X, Ge L, Liu J, Yang X. Functional expression of the glycine transporter 1 on bullfrog retinal cones. Neuroreport. 2008;19:1667-71 pubmed publisher
    ..All these results show for the first time the functional expression of GlyT1 on bullfrog cones. ..
  44. Mease P. Further strategies for treating fibromyalgia: the role of serotonin and norepinephrine reuptake inhibitors. Am J Med. 2009;122:S44-55 pubmed publisher
    ..Pharmacologic agents that specifically target serotonin and norepinephrine reuptake may prove to be valuable tools in the treatment of fibromyalgia. ..
  45. Sidhpura N, Parsons L. Endocannabinoid-mediated synaptic plasticity and addiction-related behavior. Neuropharmacology. 2011;61:1070-87 pubmed publisher
  46. Carpenter L, Schecter J, Tyrka A, Mello A, Mello M, Haggarty R, et al. Open-label tiagabine monotherapy for major depressive disorder with anxiety. J Clin Psychiatry. 2006;67:66-71 pubmed
    ..These results suggest the potential of the SGRI tiagabine in the treatment of depression with anxiety. Large, placebo-controlled trials are needed. ..
  47. Bertsche A, Bruehl C, Pietz J, Draguhn A. Region- and pattern-specific effects of glutamate uptake blockers on epileptiform activity in rat brain slices. Epilepsy Res. 2010;88:118-26 pubmed publisher
    ..Effects of DHK were more easily reversible than those of TBOA. Thus glutamate uptake blockers exert variable effects on epileptiform activity, depending on brain region and on the mechanism of ictogenesis. ..
  48. Hersh E, Golubic S, Moore P. Analgesic update: tapentadol hydrochloride. Compend Contin Educ Dent. 2010;31:594-9; quiz 600, 603 pubmed
  49. Re D, Boucraut J, Samuel D, Birman S, Kerkerian Le Goff L, Had Aissouni L. Glutamate transport alteration triggers differentiation-state selective oxidative death of cultured astrocytes: a mechanism different from excitotoxicity depending on intracellular GSH contents. J Neurochem. 2003;85:1159-70 pubmed
  50. Ali S, Watson M, Osborne R. The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine. Auton Autacoid Pharmacol. 2004;24:103-5 pubmed
    ..These data suggest that, emodin causes contraction of the ileum by triggering the release of endogenous ACh which acts on muscarinic receptors to cause contraction of the rat isolated ileum preparation...
  51. Weng H, Chen J, Cata J. Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience. 2006;138:1351-60 pubmed
  52. Fandrick K, Feng X, Janowsky A, Johnson R, Cashman J. Bivalent biogenic amine reuptake inhibitors. Bioorg Med Chem Lett. 2003;13:2151-4 pubmed
    ..The bivalent ligand 4, comprised of linking an aryltropane by an octamethylene spacer showed high efficacy for the human dopamine transporter and had a discrimination ratio of 130. ..
  53. Matthews C, Zielke H, Parks D, Fishman P. Glutamate-pyruvate transaminase protects against glutamate toxicity in hippocampal slices. Brain Res. 2003;978:59-64 pubmed
    ..GPT is an effective neuroprotectant against glutamate excitotoxicity. When exposure is limited to endogenously released glutamate, neuroprotection by GPT is not dependent on added pyruvate. ..
  54. MANNING J, Sexton T, Childers S, Davies H. 1-Naphthyl and 4-indolyl arylalkylamines as selective monoamine reuptake inhibitors. Bioorg Med Chem Lett. 2009;19:58-61 pubmed publisher
  55. Abramochkin D, Borodinova A, Rosenshtraukh L, Nikolsky E. Both neuronal and non-neuronal acetylcholine take part in non-quantal acetylcholine release in the rat atrium. Life Sci. 2012;91:1023-6 pubmed
    ..The study demonstrates dual neuronal and non-neuronal nature of non-quantal ACh in the heart. ..
  56. Roz N, Mazur Y, Hirshfeld A, Rehavi M. Inhibition of vesicular uptake of monoamines by hyperforin. Life Sci. 2002;71:2227-37 pubmed
    ..Our results support the notion that hyperforin interferes with the storage of monoamines in synaptic vesicles, rather than being a selective inhibitor of either synaptic membrane or vesicular monoamine transporters. ..
  57. Hashioka S, Klegeris A, Monji A, Kato T, Sawada M, McGeer P, et al. Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp Neurol. 2007;206:33-42 pubmed
    ..On the other hand, the mood stabilizer and anti-manic agent lithium chloride has mixed effects on IFN-gamma-induced microglial activation. ..
  58. Ishizuka Y, Abe H, Tanoue A, Kannan H, Ishida Y. Involvement of vasopressin V1b receptor in anti-anxiety action of SSRI and SNRI in mice. Neurosci Res. 2010;66:233-7 pubmed publisher
    ..These results suggest that the anti-anxiety action of 5-HT reuptake inhibitors might partly involve V1bR regulating the anxiety behaviors. ..
  59. Levin E, Timofeeva O, Yang L, Petro A, Ryde I, Wrench N, et al. Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging. Behav Brain Res. 2010;208:319-27 pubmed publisher
    ..This study demonstrates the sex-selective, long-term behavioral alterations caused by otherwise nontoxic neonatal exposure to parathion, with effects increasingly expressed with aging. ..
  60. Soares C, Thase M, Clayton A, Guico Pabia C, Focht K, Jiang Q, et al. Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder. Menopause. 2010;17:700-11 pubmed publisher
    ..Safety and tolerability were comparable. ..
  61. Bouchard P, Panay N, de Villiers T, Vincendon P, Bao W, Cheng R, et al. Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms. Climacteric. 2012;15:12-20 pubmed publisher
    ..Adverse drug reactions were consistent with the known safety profile of desvenlafaxine, and significantly more women who received tibolone experienced episodes of bleeding compared with women who received desvenlafaxine or placebo. ..
  62. Chen Y, Chu C, Chen Y, Wang J, Hung C, Shao D. Nisoxetine produces local but not systemic analgesia against cutaneous nociceptive stimuli in the rat. Eur J Pharmacol. 2012;675:22-5 pubmed publisher
    ..That N-methyl-d-aspartate receptors may not contribute to the cutaneous (local) anesthetic effect of nisoxetine or lidocaine. ..
  63. Parejiya P, Barot B, Patel H, Shelat P, Shukla A. Innovation of novel 'Tab in Tab' system for release modulation of milnacipran HCl: optimization, formulation and in vitro investigations. Drug Dev Ind Pharm. 2013;39:1851-63 pubmed publisher
    ..Novel TITs can be a succesful once a day delivery system for highly water soluble drugs...
  64. Su X, Gebhart G. Effects of tricyclic antidepressants on mechanosensitive pelvic nerve afferent fibers innervating the rat colon. Pain. 1998;76:105-14 pubmed
  65. Noji T, Takayama M, Mizutani M, Okamura Y, Takai H, Karasawa A, et al. KF24345, an adenosine uptake inhibitor, suppresses lipopolysaccharide-induced tumor necrosis factor-alpha production and leukopenia via endogenous adenosine in mice. J Pharmacol Exp Ther. 2002;300:200-5 pubmed
    ..It is thus suggested that the adenosine uptake inhibitor has anti-inflammatory effects in vivo and represents a novel therapeutic approach to the treatment of various inflammatory diseases. ..
  66. Davies J, Johns L, Jones F. Effects of bilobalide on cerebral amino acid neurotransmission. Pharmacopsychiatry. 2003;36 Suppl 1:S84-8 pubmed
  67. Stone E, Lin Y, Ahsan R, Quartermain D. Role of locus coeruleus alpha1-adrenoceptors in motor activity in rats. Synapse. 2004;54:164-72 pubmed
  68. Alttoa A, Kõiv K, Eller M, Uustare A, Rinken A, Harro J. Effects of low dose N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine administration on exploratory and amphetamine-induced behavior and dopamine D2 receptor function in rats with high or low exploratory activity. Neuroscience. 2005;132:979-90 pubmed
    ..Together these findings suggest that LC noradrenergic neurotransmission is differently involved in dopaminergic mechanisms which mediate novelty-related vs amphetamine-induced behavior. ..
  69. Chenu F, Guiard B, Bourin M, Gardier A. Antidepressant-like activity of selective serotonin reuptake inhibitors combined with a NK1 receptor antagonist in the mouse forced swimming test. Behav Brain Res. 2006;172:256-63 pubmed
  70. Seo H, Sohi M, Patkar A, Masand P, Pae C. Desvenlafaxine succinate: a newer antidepressant for the treatment of depression and somatic symptoms. Postgrad Med. 2010;122:125-38 pubmed publisher
  71. Kothari S, Kushwah A, Kothari D. Involvement of opioid and monoaminergic pain pathways in Aegle marmelos induced analgesia in mice. Indian J Pharmacol. 2013;45:371-5 pubmed publisher
    ..A.marmelos in induced antinociception is mediated through both opioid and monoaminergic pain pathways, suggest its possible use in chronic pain. ..
  72. De Letter E, Coopman V, Cordonnier J, Piette M. One fatal and seven non-fatal cases of 4-methylthioamphetamine (4-MTA) intoxication: clinico-pathological findings. Int J Legal Med. 2001;114:352-6 pubmed
    ..In addition, individually different subjective reactions are described. Finally, the medico-legal implications of new, as yet unregistered drugs are discussed. ..
  73. Skolnick P, Popik P, Janowsky A, Beer B, Lippa A. Antidepressant-like actions of DOV 21,947: a "triple" reuptake inhibitor. Eur J Pharmacol. 2003;461:99-104 pubmed
  74. Skolnick P, Krieter P, Tizzano J, Basile A, Popik P, Czobor P, et al. Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake inhibitor. CNS Drug Rev. 2006;12:123-34 pubmed
    ..These findings provide preliminary evidence of a clinically meaningful antidepressant action with a molecule capable of inhibiting the three transmitters most closely linked to major depressive disorder. ..
  75. Ramos M, Hara C, Rocha F. Duloxetine treatment of Premenstrual Dysphoric Disorder: case reports. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:579-80 pubmed
  76. Evans K, Simon N, Dougherty D, Hoge E, Worthington J, Chow C, et al. A PET study of tiagabine treatment implicates ventral medial prefrontal cortex in generalized social anxiety disorder. Neuropsychopharmacology. 2009;34:390-8 pubmed publisher
    ..Given the pharmacological profile of tiagabine, these findings suggest that its therapeutic effects in gSAD may be mediated by GABAergic modulation within the vmPFC. ..
  77. Biezonski D, Meyer J. Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity. J Neurochem. 2010;112:951-62 pubmed publisher
    ..These results demonstrate that MDMA causes substantial regulatory changes in the expression of serotonergic markers, thus questioning the need to invoke distal axotomy as an explanation of MDMA-related serotonergic deficits. ..
  78. Stahl S, Grady M. Differences in mechanism of action between current and future antidepressants. J Clin Psychiatry. 2003;64 Suppl 13:13-7 pubmed
    ..The introduction of antidepressants with novel mechanisms of action could potentially revolutionize the treatment of depression. ..
  79. Speroff L, Gass M, Constantine G, Olivier S. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol. 2008;111:77-87 pubmed publisher
    ..Its tolerability profile is consistent with that of other serotonin-norepinephrine reuptake inhibitors.,, NCT00421031 I. ..
  80. Caldarone B, Paterson N, Zhou J, Brunner D, Kozikowski A, Westphal K, et al. The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties. J Pharmacol Exp Ther. 2010;335:762-70 pubmed publisher
    ..These findings may have implications for the potential for abuse liability in humans. ..
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