@article{MTMT:1673517,
	title = {Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake inhibitor},
	url = {https://m2.mtmt.hu/api/publication/1673517},
	author = {Skolnick, P and Krieter, P and Tizzano, J and Basile, A and Popik, P and Czobor, Pál and Lippa, A},
	doi = {10.1111/j.1527-3458.2006.00123.x},
	journal-iso = {CNS DRUG REV},
	journal = {CNS DRUG REVIEWS},
	volume = {12},
	unique-id = {1673517},
	issn = {1080-563X},
	abstract = {DOV 216,303 [(±)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochloride] is the prototype of a class of compounds referred to as "triple" reuptake inhibitors. Such compounds inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely linked to major depressive disorder. DOV 216,303 inhibits [3H]NE, [3H]5-HT, and [3H]DA uptake to the corresponding human recombinant transporters (expressed in HEK 293 cells) with IC50 values of ∼20, 14, and 78 nM, respectively. DOV 216,303 is active in tests predictive of antidepressant activity including the mouse forced swim test and reversal of tetrabenazine-induced ptosis and locomotor depression. The pharmacodynamic, pharmacokinetic, and toxicological profile of DOV 216,303 in animals prompted us to initiate clinical studies. In both single and multiple dose studies using normal volunteers, DOV 216,303 was safe and well-tolerated. Furthermore, both Cmax and AUC values were dose-proportional between 5-150 mg. The plasma concentrations of DOV 216,303 at doses >10 mg were in excess of the IC50 values for inhibition of biogenic amine reuptake. In a Phase II study designed to explore the safety and tolerability of DOV 216,303 in depressed individuals, patients received either 100 mg DOV 216,303 (50 mg b.i.d.) or 40 mg citalopram (20 mg, b.i.d.) for two weeks. A placebo arm was not employed in this study because several institutional review boards required administration of an active control to severely depressed individuals. Time dependent reductions in HAM-D scores (the primary outcome measure) were observed in both the DOV 216,303 and citalopram groups compared to baseline scores (p < 0.0001). The side effect profile was not remarkably different between treatment arms. 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. © 2006 DOV Pharmaceutical Inc.},
	keywords = {Animals; Humans; MAJOR DEPRESSION; DEPRESSION; review; human; Dose-Response Relationship, Drug; Time Factors; nonhuman; dose response; serotonin uptake inhibitor; drug effect; clinical trial; drug blood level; Dopamine Plasma Membrane Transport Proteins; drug tolerability; unclassified drug; drug safety; drug efficacy; drug mechanism; vomiting; gastrointestinal symptom; area under the curve; nausea; disease model; drug structure; fluoxetine; citalopram; diarrhea; Serotonin Plasma Membrane Transport Proteins; aza compounds; paroxetine; motor dysfunction; imipramine; drug activity; IC 50; dyspepsia; forced swimming test; drug potency; antidepressant agent; Antidepressive Agents; noradrenalin uptake inhibitor; biogenic amine; Bicyclo Compounds, Heterocyclic; Antidepressants; mazindol; Neurotransmitter Uptake Inhibitors; meteorism; dov 216303; 1 (3,4 dichlorophenyl) 3 azabicyclo[3.1.0]hexane; DOV 216,303; Pharmacology, Clinical; Norepinephrine Plasma Membrane Transport Proteins; ptosis; noradrenalin serotonin dopamine reuptake inhibitor; nisoxetine; dopamine uptake inhibitor},
	year = {2006},
	pages = {123-134},
	orcid-numbers = {Czobor, Pál/0000-0002-6361-8006}
}

@article{MTMT:1312049,
	title = {A dopamin transzporter (dat) aktivitás változása bupropion hatására 99m tc-trodat-1 spect vizsgálat depresszióban [Change of dopamine transporter activity (DAT) during the action of bupropion (in depression)]},
	url = {https://m2.mtmt.hu/api/publication/1312049},
	author = {Szabó, Zoltán and Árgyelán, Miklós and Kanyó, Balázs and Pávics, László and Janka, Zoltán},
	journal-iso = {NEUROPSYCHOPHARM HUNG},
	journal = {NEUROPSYCHOPHARMACOLOGIA HUNGARICA},
	volume = {6},
	unique-id = {1312049},
	issn = {1419-8711},
	abstract = {Bupropion has an antidepressant effect through blocking the dopamine transporter. By 99mTc-TRODAT-SPECT, we measured the baseline DAT activity of depressed patients. After 3 weeks' bupropion treatment we studied the change in DAT activity, which corresponds to the occupancy of bupropion. The average occupancy of bupropion on DAT was similar to the international findings at 20.84% in 9 depressed patients.},
	year = {2004},
	pages = {79-81},
	orcid-numbers = {Pávics, László/0000-0002-7319-1667}
}