Skip to main content
SpringerLink
Log in

Preclinical pharmacology of F-98214-TA, a novel potent serotonin and norepinephrine uptake inhibitor with antidepressant and anxiolytic properties

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Serotonin (5-HT) and norepinephrine (NE) re-uptake inhibitors (SNRIs) have been proposed to have a higher efficacy and/or faster onset of action than previously available antidepressants.

Objectives

We examined in biochemical, electrophysiological and behavioural assays the antidepressant properties of (S)-(−)-4-[(3-fluorophenoxy)-phenyl]methyl-piperidine (F-98214-TA), a compound that displays very high affinity for 5-HT and NE transporters.

Results

F-98214-TA potently inhibited the uptake of both 5-HT and NE into rat brain synaptosomes (IC50=1.9 and 11.2 nM, respectively) and decreased the electrical activity of dorsal raphe serotonergic neurones (ED50=530.3 μg/kg i.v.), an effect completely abolished by the 5-HT1A antagonist WAY100,635. In acute behavioural assays in mice, the orally administered compound potentiated the 5-hydroxy-tryptophan (5-HTP)-induced syndrome [minimal effective dose (MED)=10 mg/kg], antagonized the hypothermia induced by a high dose of apomorphine (ED50=2 mg/kg) and reduced the immobility in the tail suspension test (MED=10 mg/kg). Moreover, it also decreased the immobility in the forced swimming test in mice and rats (30 mg/kg, p.o.). Chronic administration of F-98214-TA (14 days, 30 mg kg−1 day−1, p.o.) attenuated the hyperactivity induced by olfactory bulbectomy in rats, confirming its antidepressant-like properties. Interestingly, the same dosage regimen significantly increased the social interaction time in rats, suggesting an additional potential anxiolytic activity. In most assays the compound was more potent than fluoxetine, venlafaxine and desipramine.

Conclusions

F-98214-TA is a novel SNRI that displays greater potency than other reference antidepressants in animal models predictive of antidepressant and anxiolytic activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Aghajanian GK (1978) Feedback regulation of central monoaminergic neurons: evidence from single cell recording studies. In: Youdin MBH, Lovenberg W, Sharman DF, Lagnado JR (eds) Essays in neurochemistry and neuropharmacology. Wiley, New York, pp 1–32

    Google Scholar 

  • Anderson IM (1998) SSRIs versus tricyclic antidepressants in depressed impatients: a meta-analysis of efficacy and tolerability. Depress Anxiety 7:11–17

    Article  PubMed  Google Scholar 

  • Anderson IM (2001) Meta-analytical studies on new antidepressants. Br Med Bull 57:161–178

    Article  PubMed  CAS  Google Scholar 

  • Béique JC, De Montigny C, Blier P, Debonnel G (1999) Venlafaxine: discrepancy between in vivo 5-HT and NE reuptake blockade and affinity for reuptake sites. Synapse 32:198–211

    Article  PubMed  Google Scholar 

  • Bel N, Artigas F (1999) Modulation of the extracellular 5−hydroxytryptamine brain concentrations by the serotonin and noradrenaline reuptake inhibitor, milnacipran. Neuropsychopharmacology 21:745–754

    Article  PubMed  CAS  Google Scholar 

  • Benavides J, Schoemaker C, Dana Y, Claustre M, Delahaye M, Prouteau P, Manoury P, Allen J, Scatton B, Langer SZ, Arbilla S (1995) In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist Mizolastine with H1 receptors in the rodent. Arzneim Forsch 45:551–558

    CAS  Google Scholar 

  • Bjorvatn B, Fornal CA, Martín FJ, Metzler CW, Jacobs BL (2000) Venlafaxine and its interaction with WAY100,635: effects on serotonergic unit activity and behaviour in cats. Eur J Pharmacol 404:121–132

    Article  PubMed  CAS  Google Scholar 

  • Borsini F (1995) Role of the serotonergic system in the forced swimming test. Neurosci Biobehav Rev 19:377–395

    Article  PubMed  CAS  Google Scholar 

  • Borsini F, Meli A (1988) Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 94:147–160

    Article  PubMed  CAS  Google Scholar 

  • Borsini F, Podhorna J, Marazziti D (2002) Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology 163:121–141

    Article  PubMed  CAS  Google Scholar 

  • Brocco M, Dekeyne A, Veiga S, Girardon S, Millan MJ (2002) Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents. Pharmacol Biochem Behav 71:667–680

    Article  PubMed  CAS  Google Scholar 

  • Brunello N, Racagni G (1998) Rationale for the development of noradrenaline reuptake inhibitors. Hum Psychopharmacol 13:S13–S19

    Article  CAS  Google Scholar 

  • Burnett FE, Dinan TG (1998) Venlafaxine. Pharmacology and therapeutic potential in the treatment of depression. Hum Psychopharmacol 13:153–162

    Article  CAS  Google Scholar 

  • Buus Lassen J (1978) Potent and long-lasting potentiation of two 5-hydroxytryptophan-induced effects in mice by three selective 5-HT uptake inhibitors. Eur J Pharmacol 47:351–358

    Article  CAS  Google Scholar 

  • Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT (2001) Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 25:871–880

    Article  PubMed  CAS  Google Scholar 

  • Bymaster FP, McNamara RK, Tran PV (2003) New approaches to developing antidepressants by enhancing monoaminergic neurotransmission. Expert Opin Investig Drugs 12:531–543

    Article  PubMed  CAS  Google Scholar 

  • Cairncross KD, Cox B, Forster C, Wren AF (1978) A new model for the detection of antidepressant drugs: olfactory bulbectomy in the rat compared with existing models. J Pharmacol Methods 1:131–143

    Article  CAS  Google Scholar 

  • Cervo L, Grignaschi G, Rossi C, Samanin R (1991) Role of serotonergic neurons in the effect of sertraline in rats in the forced swimming test. Eur J Pharmacol 196:217–222

    Article  PubMed  CAS  Google Scholar 

  • Cheng YC, Prusoff WH (1973) Relationship between inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I 50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108

    Article  PubMed  CAS  Google Scholar 

  • Clerc G, Milnacipran/Fluvoxamine Study Group (2001) Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine. Int Clin Psychopharmacol 16:145–151

    Article  CAS  Google Scholar 

  • Cryan JF, Mc Grath C, Leonard BE, Norman TR (1998) Combining pindolol and paroxetine in an animal model of chronic antidepressant action. Can early onset of action be detected? Eur J Pharmacol 352:23–28

    Article  PubMed  CAS  Google Scholar 

  • Czachura JF, Rasmussen K (2000) Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal rapphe nucleus of the rat. Naunyn-Schmiedeberg's Arch Pharmacol 362:266–275

    Article  CAS  Google Scholar 

  • Dalvi A, Lucki I (1999) Murine models of depression. Psychopharmacology 147:14–16

    Article  PubMed  CAS  Google Scholar 

  • David DJP, Renard CE, Jolliet P, Hascoët M, Bourin M (2003) Antidepressant-like effects in various mice strains in the forced swimming test. Psychopharmacology 166:373–382

    PubMed  CAS  Google Scholar 

  • de Oliveira RA, Cunha GM, Borges KD, de Bruin GS, dos Santos-Filho EA, Viana GS, de Bruin VM (2004) The effect of venlafaxine on behaviour, body weight and striatal monoamine levels on sleep-deprived female rats. Pharmacol Biochem Behav 79:499–506

    Article  PubMed  CAS  Google Scholar 

  • Dekeyne A, Denorme B, Monneyron S, Millan MJ (2000) Citalopram reduces social interaction in rats by activation of serotonin (5-HT) (2C) receptors. Neuropharmacology 39:1114–1117

    Article  PubMed  CAS  Google Scholar 

  • Detke MJ, Rickels M, Lucki I (1995) Active behaviours in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121:66–72

    Article  PubMed  CAS  Google Scholar 

  • Domenech T, Beleta J, Palacios JM (1997) Characterization of human serotonin 1D and 1B receptors using [3H]-GR-125743, a novel radiolabelled serotonin 5-HT1D/1B receptor antagonist. Naunyn-Schmiedeberg's Arch Pharmacol 356:328–334

    Article  CAS  Google Scholar 

  • Duxon MS, Starr KR, Upton N (2000) Latency to paroxetine-induced anxiolysis in the rat is reduced by co-administration of the 5-HT1A receptor antagonist WAY100635. Brit J Pharmacol 130:1713–1719

    Article  CAS  Google Scholar 

  • Entsuah R, Derivan A, Kikta D (1998) Early onset of antidepressant action of venlafaxine: pattern analysis in intent-to-treat patients. Clin Ther 20:517–526

    Article  PubMed  CAS  Google Scholar 

  • Erdbrügger W, Raulf M, Otto T, Michel MC (1995) Does [3H]-2-methoxy-Idazoxan (RX821002) detect more alpha2-adrenoceptor agonist high affinity sites than [3H]-Rauwolscine? A comparison of nine tissues and cell lines. J Pharmacol Exp Ther 273:1287–1294

    PubMed  Google Scholar 

  • File SE, Gonzalez LE, Andrews N (1996) Comparative study of pre- and postsynaptic 5-HT1A receptor modulation of anxiety in two ethological animal tests. J Neurosci 16:4810–4815

    PubMed  CAS  Google Scholar 

  • Fuxe K, Sjöqvist F (1972) Hypothermic effect of apomorphine in the mouse. J Pharm Pharmacol 24:702–705

    PubMed  CAS  Google Scholar 

  • Goldstein BJ, Goodnick PJ (1998) Selective serotonin reuptake inhibitors in the treatment of affective disorders-III. Tolerability, safety and pharmacoeconomics. J Psychopharmacol 12:S55–S87

    PubMed  CAS  Google Scholar 

  • Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA (2004) Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol 24:389–399

    Article  PubMed  CAS  Google Scholar 

  • Goodnick PJ, Goldstein BJ (1998) Selective serotonin reuptake inhibitors in the treatment of affective disorders-II. Efficacy and quality of life. J Psychopharmacol 12:S21–S54

    PubMed  CAS  Google Scholar 

  • Hess EJ, Battaglia G, Norman AB, Iorio LC, Creese I (1986) Guanine nucleotide regulation of agonist interactions at [3H]-SCH 23390-labeled D1 dopamine receptors in rat striatum. Eur J Pharmacol 121:31–38

    Article  PubMed  CAS  Google Scholar 

  • Hindmarch I (2001) Expanding the horizons of depression: beyond the monoamine hypothesis. Hum Psychopharmacol Clin Exp 16:203–218

    Article  PubMed  CAS  Google Scholar 

  • Hughes ZA, Stanford SC (1998) Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs. Br J Pharmacol 124:1141–1148

    Article  PubMed  CAS  Google Scholar 

  • Kelly JP, Wrynn AS, Leonard BE (1997) The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 74:299–316

    Article  PubMed  CAS  Google Scholar 

  • Kent JM, Coplan JD, Gorman JM (1998) Clinical utility of the selective reuptake inhibitors in the spectrum of anxiety. Biol Psychiatry 44:812–824

    Article  PubMed  CAS  Google Scholar 

  • Kerrigan F (1998) Antidepressant patents: 1995–1997. Expert Opin Ther Pat 8:439–460

    Article  CAS  Google Scholar 

  • Koch S, Hemrick-Luecke SK, Thompson LK, Evans DC, Threlkeld PG, Nelson DL, Perry KW, Bymaster FP (2003) Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. Neuropharmacology 45:935–944

    Article  PubMed  CAS  Google Scholar 

  • Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113

    PubMed  CAS  Google Scholar 

  • Lucki I, Singh A, Kreiss DS (1994) Antidepressant-like behavioural effects of serotonin receptor agonists. Neurosci Biobehav Rev 18:85–95

    Article  PubMed  CAS  Google Scholar 

  • McGrath C, Norman TR (1998) The effect of venlafaxine treatment on the neurochemical changes in the olfactory bulbectomised rat. Psychopharmacology 136:394–401

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ (2004) The role of monoamines in the actions of established and “novel” antidepressant agents: a critical review. Eur J Pharmacol 500:371–384

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Gobert A, Lejeune F, Newman-Tancredi A, Rivet JM, Auclair A, Peglion JL (2001a) S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. J Pharmacol Exp Ther 298:565–580

    PubMed  CAS  Google Scholar 

  • Millan MJ, Dekeyne A, Papp M, La Rochelle CD, MacSweeny C, Peglion JL, Brocco M (2001b) S33005, a novel ligand at both serotonin and norepinephrine transporters: II. behavioural profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. J Pharmacol Exp Ther 298:581–591

    PubMed  CAS  Google Scholar 

  • Mochizuki D, Tsujita R, Yamada S, Kawasaki K, Otsuka Y, Hashimoto S, Hattori T, Kitamura Y, Miki N (2002) Neurochemical and behavioural characterization of milnacipran, a serotonin and noradrenaline reuptake inhibitor in rats. Psychopharmacology 162:323–332

    Article  PubMed  CAS  Google Scholar 

  • Montgomery SA (1995) Rapid onset of action of venlafaxine. Int Clin Psychopharmacol 10:21–27

    Article  PubMed  Google Scholar 

  • Muth EA, Moyer JA, Haskins JT, Andree TH, Husbands GEM (1991) Biochemical, neurophysiological, and behavioural effects of Wy-45,233 and other identified metabolites of the antidepressant venlafaxine. Drug Dev Res 23:191–199

    Article  CAS  Google Scholar 

  • Nelson JC, Mazure CM, Bowers MB, Jatlow PI (1991) A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of depression. Arch Gen Psychiatry 48:303–307

    PubMed  CAS  Google Scholar 

  • Nelson JC, Mazure CM, Jatlow PI, Bowers MB, Price LH (2004) Combining norepinephrine and serotonin reuptake inhibition mechanism for treatment of depression: a double-blind, randomized study. Biol Psychiatry 55:296–300

    Article  PubMed  CAS  Google Scholar 

  • Nielsen DM, Carey GL, Gold LH (2004) Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice. Eur J Pharmacol 499:135–146

    Article  PubMed  CAS  Google Scholar 

  • Orjales A, Alonso-Cires L, López-Tudanca PL, Tapia I, Labeaga L, Mosquera R (2000) Sintesis and 5-HT3 receptor affinity of new quinolinecarboxylic acid derivatives. Drug Des Discov 16:271–279

    PubMed  CAS  Google Scholar 

  • Orjales A, Mosquera R, Toledo A, Pumar MC, García N, Cortizo L, Labeaga L, Innerarity A (2003) Syntheses and binding studies of new [(aryl)(aryloxy)methyl] piperidine derivatives and related compounds as potential antidepressant drugs with high affinity for serotonin (5-HT) and norepinephrine (NE) transporters. J Med Chem 46:5512–5532

    Article  PubMed  CAS  Google Scholar 

  • Oshita M, Kigoshi S, Muramatsu I (1991) Three distinct binding sites for [3H]-prazosin in the rat cerebral cortex. Br J Pharmacol 104:961–965

    PubMed  CAS  Google Scholar 

  • Overstreet DH (1993) The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Biobehav Rev 17:51–68

    Article  PubMed  CAS  Google Scholar 

  • Owens MJ, Morga WN, Plott SJ, Nemeroff CB (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 283:1305–1322

    PubMed  CAS  Google Scholar 

  • Popik P, Vetulani J (1993) Similar action of imipramine and arginine-vasopressin in the social interaction test. Pol J Pharmacol 45:323–325

    PubMed  CAS  Google Scholar 

  • Porsolt R, Bertin A, Jalfre M (1978a) Behavioural despair in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294

    Article  PubMed  CAS  Google Scholar 

  • Porsolt R, Anton G, Blavet N, Jalfre M (1978b) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391

    Article  PubMed  CAS  Google Scholar 

  • Redmond AM, Kelly JP, Leonard BE (1999) The determination of the optimal dose of milnacipran in the olfactory bulbectomized rat model of depression. Pharmacol Biochem Behav 62:619–623

    Article  PubMed  CAS  Google Scholar 

  • Redrobe JP, Bourin M, Colombel MC, Baker GB (1998) Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity. Psychopharmacology 138:1–8

    Article  PubMed  CAS  Google Scholar 

  • Rénéric JP, Lucki I (1998) Antidepressant behavioural effects by dual inhibition of monoamine reuptake in the rat forced swimming test. Psychopharmacology 136:190–197

    Article  PubMed  Google Scholar 

  • Rickels K, Pollack MH, Sheehan DV, Haskins JT (2000) Efficacy of extended-release venlafaxine in non-depressed outpatients with generalized anxiety disorder. Am J Psychiatry 157:968–974

    Article  PubMed  CAS  Google Scholar 

  • Ripoll N, David DJP, Dailly E, Hascoët M, Bourin M (2003) Antidepressant-like effects in various mice strains in the tail suspension test. Behav Brain Res 143:193–200

    Article  PubMed  CAS  Google Scholar 

  • Rogóz Z, Dziedzicka-Wasylewska M, Maj J (1998) The pharmacological profile of venlafaxine, a new antidepressant, given acutely. Pol J Pharmacol 50:107–115

    PubMed  Google Scholar 

  • Saiz−Ruiz J, Ibanez A, Díaz-Marsa M, Arias F, Padin J, Martin-Carrasco M, Montes JM, Ferrando L, Carrasco JL, Martin-Ballesteros E, Jorda L, Chamorro L (2002) Efficacy of venlafaxine in major depresion resistant to selective serotonin reuptake inhibitors. Prog Neuropsychopharmacol Biol Psychiatry 26:1129–1134

    Article  PubMed  CAS  Google Scholar 

  • Sanchez C, Meier E (1997) Behavioural profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike? Psychopharmacology 129:197–205

    Article  PubMed  CAS  Google Scholar 

  • Stenger A, Couzinier J-P, Briley M (1987) Psychopharmacology of midalcipran, 1-phenyl-1-diethyl-amino-carbonyl-2-aminomethylcyclopropane hydrochloride (F 2207), a new potential antidepressant. Psychopharmacology 91:147–153

    Article  PubMed  CAS  Google Scholar 

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370

    Article  PubMed  CAS  Google Scholar 

  • Thase ME (1998) Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry 59:502–508

    PubMed  CAS  Google Scholar 

  • Thase ME, Entsuah AR, Rudolph RL (2001) Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 178:234–241

    Article  PubMed  CAS  Google Scholar 

  • Tran PV, Bymaster FP, McNamara RK, Potter WZ (2003) Dual monoamine modulation for improved treatment of major depressive disorder. J Clin Psychopharmacol 23:78–86

    Article  PubMed  CAS  Google Scholar 

  • Van Der Heyden JAM, Molewijk E, Olivier B (1987) Strain differences in response to drugs in the tail suspension test for antidepressant activity. Psychopharmacology 92:127–130

    Article  PubMed  Google Scholar 

  • Watson M, Roeske WR, Yamamura HI (1996) [3H]-Pirenzepine and [3H]-Quinuclidinyl benzilate binding to rat cerebral cortical and cardiac muscarinic cholinergic sites: characterization and regulation of antagonist binding to putative muscarinic subtypes. J Pharmacol Exp Ther 237:419–427

    Google Scholar 

  • Weilburg JB, Rosenbaum JF, Biederman J, Sachs GS, Pollack MH, Kelly K (1989) Fluoxetine added to non-MAOI antidepressants converts nonresponders to responders: a preliminary report. J Clin Psychiatry 50:447–449

    PubMed  CAS  Google Scholar 

  • Wong ML, Licinio J (2001) Research and treatment approaches to depression. Nat Rev Neurosci 2:343–351

    Article  PubMed  CAS  Google Scholar 

  • Zajecka JM, Albano D (2004) SNRIs in the management of acute major depressive disorder. J Clin Psychiatry 65:11–18

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was in part supported by the Ministry of Science and Technology of Spain (PROFIT 2000–2003, BFI 01/0592 and 1FD 97/1597) and the Department of Industry, Commerce and Tourism of the Basque Country Government (INTEK 2000–2003). R. Pena was granted by the Ministry of Science and Technology of Spain (MIT fellowship). We thank Begoña González, Gaizka Akarregi, Iñaki Marcos, Lourdes Lanza and Ma. Josefa Castillo for technical assistance.

Author information

Author notes

  1. José Angel Ruiz-Ortega

    Present address: Department of Pharmacology, University of the Basque Country, Leioa, 48940, Spain

Authors and Affiliations

  1. Department of Research, FAES FARMA, S. A., Máximo Aguirre 14, Leioa, 48940, Vizcaya, Spain

    Inés Artaiz, Arturo Zazpe, Ana Innerárity, Elena del Olmo, Ruth Pena, Luis Labeaga & Aurelio Orjales

  2. Department of Physiology and Pharmacology, University of Cantabria, Avda. de los Castros s/n, Santander, Cantabria, 39005, Spain

    Alvaro Díaz, José Angel Ruiz-Ortega, Elena Castro, Ruth Pena & Angel Pazos

Authors
  1. Inés Artaiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arturo Zazpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Innerárity
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena del Olmo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alvaro Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José Angel Ruiz-Ortega
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elena Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ruth Pena
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Luis Labeaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Angel Pazos
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Aurelio Orjales
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aurelio Orjales.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Artaiz, I., Zazpe, A., Innerárity, A. et al. Preclinical pharmacology of F-98214-TA, a novel potent serotonin and norepinephrine uptake inhibitor with antidepressant and anxiolytic properties. Psychopharmacology 182, 400–413 (2005). https://doi.org/10.1007/s00213-005-0087-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0087-3

Keywords

Search

Navigation