Skip to main content
SpringerLink
Log in

New Pharmacological Treatment Approaches for Anxiety Disorders

  • Chapter
Anxiety and Anxiolytic Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 169))

Abstract

New developments in the pharmacological treatment of anxiety disorders will have distinct backgrounds: characterization of pathophysiological processes including evolving techniques of genomics and proteomics will generate new drug targets. Drug development design will generate new pharmacological substances with specific action at specific neurotransmitter and neuropeptide receptors or affecting their reuptake and metabolism. New anxiolytic drugs may target receptor systems that only recently have been linked to anxiety-related behavior. This includes the N-methyl-D-aspartate (NMDA), S-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and the cannabinoid receptors. In addition, signal transduction pathways, neurotrophic factors, and gases such as nitric oxide or carbon monoxide may be new drug targets. Combining psychopharmacological and psychotherapeutical interventions is a further field where benefits for the treatment of anxiety disorders could be achieved. Although the road of drug development is arduous, improvements in the pharmacological treatment of anxiety disorders are expected for the near future.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akiyoshi J, Moriyama T, Isogawa K, Miyamoto M, Sasaki I, Kuga K, Yamamoto H, Yamada K, Fugii I (1996) CCk-4-induced calcium mobilization in T cells is enhanced in panic disorder. J Neurochem 66:1610–1615

    PubMed  Google Scholar 

  • Bale TL, A Contarino, Smith GW, Chan R, LH Gold, Sawchenko PE, GF Koob, WW Vale, KF Lee (2000) Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behavior and are hypersensitive to stress. Nat Genet 24:410–414

    Article  PubMed  Google Scholar 

  • Bauer E, LeDoux JE, Nader K (2001) Fear conditioning and LTP in the lateral amygdala are sensitive to the same stimulus contingencies. Nat Neurosci 4:687–688

    Article  PubMed  Google Scholar 

  • Bhattacharya SK, Chakrabarti A, Sandler M, Glover V (1996) Anxiolytic activity of intracerebroventricularly administered atrial natriuretic peptide in the rat. Neuropsychopharmacology 15:199–206

    Article  PubMed  Google Scholar 

  • Bing O, Moller C, Engel JA, Soderpalm B, Heilig M (1993) Anxiolytic-like action of centrally administered galanin. Neurosci Lett 164:17–20

    Article  PubMed  Google Scholar 

  • Birnbaum S, Gobeske K, Auerbach J, Taylor J, Arnsten A (1999) A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry 46:1266–1274

    Article  PubMed  Google Scholar 

  • Biro E, Sarnyai Z, Penke B, Szabo G, Telegdy G (1999) Role of endogenous corticotropin-releasing factor in mediation of neuroendocrine and behavioral response to cholecystokinin octapeptide sulfate ester in rats. Neuroendocrinology 57:340–345

    Google Scholar 

  • Brambilla F, Bellodi L, Perna G, Garberi A, Panerai A, Sacerdote P (1993) T cell cholecystokinin concentrations in panic disorder. Am J Psychiatry 150:1111–1113

    PubMed  Google Scholar 

  • Bystritsky A, Rosen P, Suri R, Vapnik T (1999) Pilot open-label study of nefazodone in panic disorder. Depress Anxiety 10:137–139

    Article  PubMed  Google Scholar 

  • Caton P, Tousman SA, Quock RM (1994) Involvement of nitric oxide in nitrous oxide anxiolysis in the elevated plus-maze. Pharmacol Biochem Behav 48:689–692

    Article  PubMed  Google Scholar 

  • Ceulemens D, Hoppenbrouers M, Gelders Y, Reyntjens A (1985) The influence of ritanserin, a serotonin antagonist, in anxiety disorders: A double-blind placebo controlled study versus lorazepam. Pharmacopsychiatry 18:303–305

    PubMed  Google Scholar 

  • Chrousos G, Gold P (1992) The concept of stress and stress system disorders: overview of physical and behavioral homeostasis. JAMA 267:1244–1252

    Article  PubMed  Google Scholar 

  • Cohen P (2002) Protein kinases—the major drug targets of the twenty-first century? Nat Rev Drug Discov 1:309–315

    Article  PubMed  Google Scholar 

  • Commons K, Valentio R (2002) Cellular basis of substance P in the periaqueductal gray and dorsal raphe nucleus. J Comp Neurol 447:82–97

    Article  PubMed  Google Scholar 

  • Conti L, Pinder R (1979) A controlled comparative trial of mianserin and diazepam in the treatment of anxiety states in psychiatric outpatients. J Int Med Res 7:185–189

    Google Scholar 

  • Coyle J, Leski M, Morrison J (2002) The diverse roles of L-glutamic acid in brain signal transduction. In: Davis K, Charney D, Coyle J, Nemeroff C (eds) Neuropsychopharmacology: and the fifth generation of progress. Lippincott Williams and Wilkins, Philadelphia, pp 71–90

    Google Scholar 

  • Crestani F, Keist R, Fritschy JM, Benke D, Vogt K, Prut L, Bluethmann H, Möhler H, Rudolph U (2002) Trace fear conditioning involves hippocampal α5 GABAA receptors. Proc Natl Acad Sci U S A 99:8980–8985

    Article  PubMed  Google Scholar 

  • Daugé V, Léna I (1998) CCK in anxiety and cognitive processes. Neurosci Biobehav Rev 22:815–825

    Article  PubMed  Google Scholar 

  • Davis M, Myers KM (2002) The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy. Biol Psychiatry 52:998–1007

    Article  PubMed  Google Scholar 

  • Dawson VL, Kizushi VM, Huang PL, Snyder SH, Dawson TM (1996) Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice. J Neurosci 16:2479–2487

    PubMed  Google Scholar 

  • de Bold AJ (1985) Atrial natriuretic factor a hormone produced by the heart. Science 230:767–770

    PubMed  Google Scholar 

  • De Montigny C (1989) Cholecystokinin tetrapeptide induces panic like attacks in healthy volunteers. Arch Gen Psychiatry 46:511–517

    PubMed  Google Scholar 

  • Dolmetsch R, Pajvani U, Fife K, Spotts JM, Greenberg ME (2001) Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway. Science 294:333–339

    Article  PubMed  Google Scholar 

  • Duman R, Malberg J, Nakagawa S, D'Sa C (2000) Neuronal plasticity and survival in mood disorders. Biol Psychiatry 48:732–739

    Article  PubMed  Google Scholar 

  • Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606

    PubMed  Google Scholar 

  • Dumont Y, Fournier A, St-Pierre S, Quirion R (1995) Characterization of neuropeptide Y binding sites in rat brain membrane preparations using [125I]Leu31, [Pro34]peptide YY and [125I]peptide YY3-36 as selective Y1 and Y2 radioligands. J Pharmacol Exp Ther 272:673–680

    PubMed  Google Scholar 

  • Dunn A, Berridge CW (1990) Physiological and behavioral responses to corticotropin releasing factor administration: Is CRF a mediator of anxiety or stress response. Brain Res Brain Res Rev 15:71–100

    Article  PubMed  Google Scholar 

  • Dunn R, Reed TA, Copeland PD, Frye CA (1998) The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without tolerance in rats following subchronic administration. Neuropharmacology 37:899–904

    Article  PubMed  Google Scholar 

  • Freeman AR, Westphal J, Norris G, Roggero B, Webb P, Freeman K (1997) Efficacy of ondansetron in the treatment of generalized anxiety disorder. DepressAnxiety 5:140–141

    Google Scholar 

  • Fritschy JM, Johnson DK, Mohler H, Rudolph U (1998) Independent assembly and subcellular targeting of GABAA receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo. Neurosci Lett 249:99–102

    Article  PubMed  Google Scholar 

  • Griebel G (1999) Is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders. Pharmacol Ther 82:1–61

    PubMed  Google Scholar 

  • Griebel G, Perrault G, Soubrie P (2001) Effects of SR48968, a selective non-peptide NK2 receptor antagonist on emotional processes in rodents. Psychopharmacology (Berl) 158:241–251

    Article  PubMed  Google Scholar 

  • Griebel G, Simiand J, Serradeil-LeGal C, Wagnon J, Pascal M, Scatton B, Maffrand JP, Soubrie P (2002) Anxiolytic-and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR 149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci U S A 99:6370–6375

    Article  PubMed  Google Scholar 

  • Griffin LD, Mellon SH (1999) Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci U S A 96:13512–13517

    Article  PubMed  Google Scholar 

  • Guidotti A, Costa E (1998) Can the antidysphoric and anxiolytic profiles of selective serotonin inhibitors be related to their ability to increase brain 3α,5α-tetrahydroprogesterone (allopregnanolone) availability? Biol Psychiatry 44:865–873

    Article  PubMed  Google Scholar 

  • Harro J, Vasar E, Bradwejn J (1993) Cholecystokinin in animal and human research of anxiety. Trends Pharmacol Sci 14:244–249

    Article  PubMed  Google Scholar 

  • Heilig M, McLeod S, Brot M, Heinrichs SC, Menzaghi F, Koob GF, Britton KT (1993) Anxiolytic-like action of neuropeptide Y mediation by Y1 receptors in amygdala, and dissociation from food intake effects. Neuropsychopharmacology 8:357–363

    PubMed  Google Scholar 

  • Hernando F, Schoots O, Lolait SJ, Burbach JPH (2001) Immunohistochemical localization of the vasopressin V1b receptor in the rat brain and pituitary gland: anatomical support for its involvement in the central effects of vasopressin. Endocrinology 142:1659–1668

    Article  PubMed  Google Scholar 

  • Holmes A, Yang RJ, Murphy DL, Crawley JN (2002) Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 27:914–923

    Article  PubMed  Google Scholar 

  • Holmes A, Kinney JW, Wrenn CC, Li Q, Yang RJ, Ma L, Vishwanath J, Saavedra MC, Inner-field CE, Jacoby AS, Shine J, Iismaa TP, Crawley JN (2003) Galanin GAL-R1 receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze. Neuropsychopharmacology 28:1031–1044

    PubMed  Google Scholar 

  • Holsboer F (1999) The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatr Res 33:181–214

    Article  PubMed  Google Scholar 

  • Hoyer D, Hannon J, Martin G (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554

    Article  PubMed  Google Scholar 

  • Kellner M, Wiedemann K, Holsboer F (1992) ANF inhibits the CRH-stimulated secretion of ACTH and cortisol in man. Life Sci 50:1835–1842

    Article  PubMed  Google Scholar 

  • Kellner M, Herzog L, Yassouridis A, Holsboer F, Wiedemann K (1995) A possible role of atrial natriuretic hormone in pituitary-adrenocortical unresponsiveness in lactate-induced panic disorder. Am J Psychiatry 152:1365–1367

    PubMed  Google Scholar 

  • Kennedy JL, Bradwein J, Koszycki D (1999) Investigation of cholecystokinin system genes in panic disorder. Mol Psychiatry 4:284–285

    Article  PubMed  Google Scholar 

  • Kennett G, Whitton P, Shah K, Curzon G (1989) Anxiogenic like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists. Eur J Pharmacol 164:445–454

    Article  PubMed  Google Scholar 

  • Khisti RT, Chopde CT, Jain SP (2000) Antidepressant-like effect of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in mice forced swim test. Pharmacol Biochem Behav 67:137–143

    Article  PubMed  Google Scholar 

  • Kishimoto T, Radulovic M, Lin CR, Hooshmand F, Hermanson O, Rosenfeld MG, Spiess J (2000) Deletion of the CRH2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nat Genet 24:415–419

    Article  PubMed  Google Scholar 

  • Kramer MS, Cutler NR, Ballenger JC, Patterson WM, Mendels J (1995) A placebo-controlled trial of L-365,260, a CCK antagonist, in panic disorder. Biol Psychiatry 37:462–466

    Article  PubMed  Google Scholar 

  • Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek IJ, Reines SA, Snavely D, Wyatt-Knowles E, Hayle EJ (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281:1640–1645

    Article  PubMed  Google Scholar 

  • Kriegsfeld LJ, Dawson TM, Dawson VL, Nelson RJ, Snyder SH (1997) Aggressive behavior in male mice lacking the gene for neuronal nitric oxide synthase requires testosterone. Brain Res 769:66–70

    Article  PubMed  Google Scholar 

  • Landgraf R, Gerstberger R, Montkowski A, Probst JC, Wotjak CT, Holsboer F, Engelmann M (1995) V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci 15:4250–4258

    PubMed  Google Scholar 

  • Li B-M, Mei ZT (1994) Delayed response deficit induced by local injection of the alpha-2 adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys. Behav Neural Biol 62:134–139

    PubMed  Google Scholar 

  • Li S, Yusuke O, Yang D, Quock RM (2003b) Antagonism of nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration procedure by pharmacologic disruption of endogenous nitric oxide function. Psychopharmacology (Berl) 166:366–372

    PubMed  Google Scholar 

  • Li X, Tizzano JP, Griffey K (2001) Antidepressant-like action of an AMPA receptor potentiator (LY392098). Neuropsychopharmacology 40:1028–1033

    Article  Google Scholar 

  • Liebsch G, Landgraf R, Engelmann M, Lörscher P, Holsboer F (1999) Differential behavioural effects of chronic infusion of CRH1 and CRH2 receptor antisense oligonucleotides into the rat brain. J Psychiatr Res 33:153–163

    Article  PubMed  Google Scholar 

  • Lin C-H, Yeh S-H, Leu T-H, Chang W-C, Wang S-T, Gean P-W (2003) Identification of calcineurin as a key signal in the extinction of fear memory. J Neurosci 23:1574–1579

    Google Scholar 

  • Lin D, Parsons L (2002) Anxiogenic-like effect of serotonin1B receptor stimulation in the rat elevated plus-maze. Pharmacol Biochem Behav 71:581–587

    Article  PubMed  Google Scholar 

  • Lines C, Challenor J, Traub M (1995) Cholecystokinin and anxiety in normal volunteers—an investigation of the anxiogenic properties of pentagastrin and reversal by the cholecystokinin receptor subtype-b-antagonist L-365,260. Br J Clin Pharmacol 39:235–242

    PubMed  Google Scholar 

  • Lolait SJ, O'Carroll AM, Mahan LC, Felder CC, Button D, Young III WS (1995) Extrapituitary expression of the rat V1b vasopressin receptor gene. Proc Natl Acad Sci USA 92:6783–6787

    PubMed  Google Scholar 

  • Low K, Crestani F, Kleist R, Benke D, Brunig I, Benson J, Möhler H (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290:131–140

    Article  PubMed  Google Scholar 

  • Lu KT, Walker DL, Davis M (2001) Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle. J Neurosci 21:RC162

    Google Scholar 

  • Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232:1004–1007

    PubMed  Google Scholar 

  • Mansuy I, Mayford M, Jacob B, Kandel ER, Bach ME (1998) Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 92:39–49

    Article  PubMed  Google Scholar 

  • Maragakis N, Rothstein J (2001) Glutamate transports in neurologic disease. Arch Neurol 58:365–370

    Article  PubMed  Google Scholar 

  • Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418:530–534

    Article  PubMed  Google Scholar 

  • McKeman R, Rosdahl T, Reynolds D, Sur C, Wafford K, Atack J (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA-A receptor alpha-1 subtype receptors. Nat Neurosci 3:587–592

    Article  PubMed  Google Scholar 

  • Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, Matsui T, Noda T, Takuguchi S, Takata Y, Kawanami T, Funakoshi A (2002) Anxiety-related behaviors in cholecystokinin-A,B, and AB receptor gene knockout mice in the plus-maze. Neurosci Lett 335:115–118

    Article  PubMed  Google Scholar 

  • Möhler H, Fritschy JM, Rudolph U (2002) A new benzodiazepine pharmacology. J Pharmacol Exp Ther 300:2–8

    Article  PubMed  Google Scholar 

  • Moller C, Sommer W, Thorsell A, Heilig M (1999) Anxiogenic-like action of galanin after intra-amygdala administration in the rat. Neuropsychopharmacology 21:507–512

    Article  PubMed  Google Scholar 

  • Morilak DA, Cecchi M, Khoshbouei H (2003) Interactions of norepinephrine and galanin in the central amygdala and lateral bed nucleus of the stria terminalis modulate the behavioral response to acute stress. Life Sci 73:715–726

    Article  PubMed  Google Scholar 

  • Myers KM, Davis M (2002) Behavioral and neural analysis of extinction. Neuron 36:567–584

    Article  PubMed  Google Scholar 

  • Nelson RJ, Demas GE, Huang PL, Fishman MC, Dawson VL, Dawson TM, Snyder SH (1995) Behavioral abnormalities in mice lacking neuronal nitric oxide synthase. Nature 378:383–386

    Article  PubMed  Google Scholar 

  • Ostrowski NL, Lolait SJ, Bradley DJ, O'Carroll AM, Brownstein MJ, Young WS (1992) Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in liver, kidney, pituitary and brain. Endocrinology 131:533–535

    Article  PubMed  Google Scholar 

  • Otsuka M, Yoshioka K (1993) Neurotransmitter functions of mammalian tachykinins. Physiol Rev 73:229–308

    PubMed  Google Scholar 

  • Palmiter RD, Erickson JC, Hollopeter G, Baraban SC, Schwartz MW (1998) Life without neuropeptide Y. Recent Prog Horm Res 53:163–199

    PubMed  Google Scholar 

  • Pande A, Davidson J, Jefferson J, Janney C, Katzelnick D, Weisler R (1999b) Treatment of social phobia with gabapentin: A placebo-controlled study. J Clin Psychopharmacol 19:341–348

    Article  PubMed  Google Scholar 

  • Pande A, Davidson J, Jefferson J, Janney C, Chouinard G, Lydiard R (2000) Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol 20:467–471

    Article  PubMed  Google Scholar 

  • Pande AC, Greiner M, Adams JB (1999a) Placebo-controlled trial of the CCK-B antagonist, CI-988 in panic disorder. Mol Psychiatry 46:860–862

    Google Scholar 

  • Patchev VK, Montkowski A, Rouskova D, Koranyi L, Holsboer F, Almeida O (1997) Neonatal treatment of rats with the neuroactive steroid tetrahydrodeoxycorticosterone (THDOC) abolishes the behavioral and neuroendocrine consequences of adverse early life events. J Clin Invest 99:962–966

    PubMed  Google Scholar 

  • Paul SM, RH Purdy (1992) Neuroactive steroids. FASEB J 6:2311–2322

    PubMed  Google Scholar 

  • Pigott T, Zohar J, Hill J, Bernstein S, Grover G, Zohar-Kadouch R (1991) Metergoline blocks the behavioral and neuroendocrine effects of orally administered m-chlorophenylpiperazine in patients with obsessive compulsive disorder. Biol Psychiatry 29:418–426S

    Article  PubMed  Google Scholar 

  • Pitman R, Sanders K, Zusman R, Healy A, Cheema F, Lasko N (2002) Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 51:189–192

    Article  PubMed  Google Scholar 

  • Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, Hodges L, Davis M (2004) Cognitive enhancers as adjuncts to psychotherapy. Arch Gen Psychiatry 61:1136–1144

    Article  PubMed  Google Scholar 

  • Ribeiro L, Busnello J, Kauer-Sant'Anna M, Madruga M, Quevedo J, Busnello E (2001) Mirtazapine versus fluoxetine in the treatment of panic disorder. Braz J Med Biol Res 34:1303–1307

    PubMed  Google Scholar 

  • Rickels K, Pollack M, Lydiard R (2002) Efficacy and safety of pregabalin and alprazolam in generalized anxiety disorder. American Psychiatric Association Annual Meeting, vol. NR 162. American Psychiatric Press, Philadelphia

    Google Scholar 

  • Romeo E, A Ströhle, F di Michele, G Spaletta, B Hermann, F Holsboer, A Pasini, R Rupprecht (1998) Effects of antidepressant treatment on neuroactive steroids in major depression. Am J Psychiatry 155:910–913

    PubMed  Google Scholar 

  • Rupprecht R, Holsboer F (1999) Neuroactive steroids: mechanisms of action and neuropsy-chopharmacological perspectives. Trends Neurosci 22:410–416

    Article  PubMed  Google Scholar 

  • Sajdyk TJ, Schober DA, Gehlert DR (2002) Neuropeptide Y receptor subtypes in the basolateral nucleus of the amygdala modulate anxiogenic responses in rats. Neuropharmacology 43:1165–1172

    Article  PubMed  Google Scholar 

  • Santarelli L, Gobbi G, Debs P, Sibille E, Blier P, Hen R (2001) Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function. Proc Natl Acad Sci USA 98:1912–1917

    Article  PubMed  Google Scholar 

  • Scatton B, Deportere H, George P, Servin M, Benavides J, Schoemaker H, Perrault G (2000) Selectivity for GABAA receptor α subunits as a strategy for developing hypnoselective and anxioselective drugs. Int J Neuropsychopharmacol 3:S41–S43

    Google Scholar 

  • Schneier F, Garfinkel R, Kennedy B, Campeas R, Fallon B, Marshall R (1996) Ondansetron in the treatment of panic disorder. Anxiety 2:199–202

    Article  PubMed  Google Scholar 

  • Shlik J, Aluoja A, Vasar V, Vasar E, Podar T, Bradwein J (1997) Effects of citalopram on behavioral, cardiovascular, and neuroendocrine response to cholecystokinin tetrapeptide challenge in patients with panic disorder. J Psychiatry Neurosci 22:332–340

    PubMed  Google Scholar 

  • Skutella T, Montkowski A, Stöhr A, Probst JR, Landgraf R, Holsboer F, Jirikowski GF (1994) Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide treatment attenuates social defeat-induced anxiety in rats. Cell Mol Neurobiol 14:579–588

    PubMed  Google Scholar 

  • Skutella T, Probst JC, Renner U, Holsboer F, Behl C (1998) Corticotropin-releasing hormone receptor (type I) antisense targeting reduces anxiety. Neuroscience 85:795–805

    Article  PubMed  Google Scholar 

  • Smith GW, Aubry J-M, Dellu F, Contarino A, Bilezjian LM, Gold LH, Hause C, Bentley CA, Sawchenko PE, Koob GF, Vale W, Lee K-F (1998) Corticotropin-releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 20:1093–1102

    Article  PubMed  Google Scholar 

  • Son H, Hawkins RD, Martin K, Kiebler M, Huang PL, Fishman MC, Kandel ER (1996) Long term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell 87:1015–1023

    Article  PubMed  Google Scholar 

  • Stenzel-Poore MP, Heinrichs SC, Rivest S, Koob GF, Vale WW (1994) Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior. J Neurosci 14:2579–2584

    PubMed  Google Scholar 

  • Ströhle A, Jahn H, Montkowski A, Liebsch G, Boll E, Landgraf R, Holsboer F, Wiedemann K (1997) Central and peripheral administration of atriopeptin is anxiolytic in rats. Neuroendocrinology 65:210–215

    PubMed  Google Scholar 

  • Ströhle A, Kellner M, Holsboer F, Wiedemann K (1998) Atrial natriuretic hormone decreases endocrine response to a combined dexamethasone corticotropin-releasing hormone test. Biol Psychiatry 43:371–375

    Article  PubMed  Google Scholar 

  • Ströhle A, Romeo E, Hermann B, di Micelle F, Spaletta G, Pasini A, Holsboer F, Rupprecht R (1999) Concentrations of 3α-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Biol Psychiatry 45:274–277

    Article  PubMed  Google Scholar 

  • Ströhle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R (2000) Fluoxetine decreases concentrations of 3α,5α-tetrahydrodeoxycorticosterone (3α,5α-THDOC) in major depression. J Psychiatr Re1 34:183–186

    Article  Google Scholar 

  • Ströhle A, Kellner M, Holsboer F, Wiedemann K (2001) Anxiolytic activity of atrial natriuretic peptide in patients with panic disorder. Am J Psychiatry 158:1514–1516

    Article  PubMed  Google Scholar 

  • Ströhle A, Romeo E, di Michele F, Pasini A, Yassouridis A, Holsboer F, Rupprecht R (2002) GABAA receptor modulatory neuroactive steroid composition in panic disorder and during paroxetine treatment. Am J Psychiatry 159:145–147

    Article  PubMed  Google Scholar 

  • Ströhle A, Romeo E, di Michele F, Pasini A, Hermann B, Gajewsky G, Holsboer F, Rupprecht F (2003) Induced panic attacks shift GABAA receptor modulatory neuroactive steroid composition. Arch Gen Psychiatry 60:161–168

    Article  PubMed  Google Scholar 

  • Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13:53–58

    Article  PubMed  Google Scholar 

  • Tanaka IS, Misono KS, Inagami T (1984) Atrial natriuretic factor in rat hypothalamus, atria and plasma: determinations by specific radioimmunoassay. Biochem Biophys Res Commun 124:663–668

    Article  PubMed  Google Scholar 

  • Thiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD (1998) Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396:366–369

    Article  PubMed  Google Scholar 

  • Thiele TE, Koh MT, Pedrazzini T (2002) Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor. J Neurosci 22:RC208

    Google Scholar 

  • Thorsell A, Rimondini R, Heilig M (2002) Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats. Neurosci Lett 332:1–4

    Article  PubMed  Google Scholar 

  • Timmusk T, Palm K, Metsis M (1993) Multiple promoter direct tissue-specific expression of rat BDNF gene. Neuron 10:475–489

    Article  PubMed  Google Scholar 

  • Timpl P, Spanagel R, Sillaber I, Kresse A, Reul JHMH, Stalla GK, Blanquet V, Steckler T, Holsboer F, Wurst W (1998) Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Nat Genet 19:162–166

    Article  PubMed  Google Scholar 

  • Tribollet E, Raufatse D, Maffrand JP, Serradeil-le Gal C (1999) Binding of the non-peptide vasopressin V1a receptor antagonist SR-49059 in the rat brain: an in vitro and in vivo autoradiographic study. Neuroendocrinology 69:113–120

    Article  PubMed  Google Scholar 

  • Tschenett A, Singewald N, Carli M, Balducci C, Salchner P, Vezzani A, Herzog H, Sperk G (2003) Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors. Eur J Neurosci 18:143–148

    Article  PubMed  Google Scholar 

  • Uzunov DP, Cooper TB, Costa E, Guidotti A (1996) Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Proc Natl Acad Sci USA 93:12599–12604

    Article  PubMed  Google Scholar 

  • Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A (1998) Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA 95:3239–3244

    Article  PubMed  Google Scholar 

  • Vale A, Green S, Montgomery AM, Shafi S (1998) The nitric oxide synthesis inhibitor LNAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test. J Psychopharmacol 12:268–272

    Google Scholar 

  • Vassout A, Veenstra S, Hauser K, Ofner S, Brugger F, Schilling W (2000) NKP608: A selective NK-1 receptor antagonist with anxiety-like effects in the social interaction and social exploration test in rats. Regul Pept 96:7–16

    Article  PubMed  Google Scholar 

  • Walker DL, Ressler KJ, Lu KT, Davis M (2002) Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear potentiated startle. J Neurosci 22:2343–2351

    PubMed  Google Scholar 

  • Wersinger SR, Ginns EI, O'Carroll AM, Lolait SJ, Young III WS (2002) Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 7:975–984

    Article  PubMed  Google Scholar 

  • Wiedemann K, Herzog L, Kellner M (1995) Atrial natriuretic hormone inhibits corticotropin-releasing hormone induced prolactin release. J Psychiatr Res 29:51–58

    Article  PubMed  Google Scholar 

  • Wiedemann K, Jahn H, Yassouridis A, Kellner M (2001) Anxiolytic activity of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks. Arch Gen Psychiatry 58:371–377

    Article  PubMed  Google Scholar 

  • Wrenn CC, Crawley JN (2001) Pharmacological evidence supporting a role for galanin in cognition and affect. Prog Neuropsychopharmacol Biol Psychiatry 25:283–299

    Article  PubMed  Google Scholar 

  • Zafra F, Hengerer B, Leibrock J (1990) Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. J Neurosci 9:3545–3550

    Google Scholar 

  • Zobel AW, Nickel T, Künzel HE, Ackl N, Sonntag A, Ising M, F Holsboer (2000) Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: The first 20 patients treated. J Psychiatr Res 34:171–181

    Article  PubMed  Google Scholar 

  • Zwansger P, Baghai TC, Schuele C, Ströhle A, Padberg F, Kathmann N, Schwarz M, Möller H-J, Rupprecht R (2001) Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology 25:699–703

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Psychiatrie und Psychotherapie, Charité Campus Mitte, Charité — Universitätsmedizin Berlin, Schumannstr. 20/21, 10117, Berlin, Germany

    A. Ströhle

Authors
  1. A. Ströhle
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Max-Planck-Institut für Psychiatrie, Kraepelinstr. 10, 80804, München, Germany

    Florian Holsboer

  2. Klinik für Psychiatrie und Psychotherapie, Charité Campus Mitte, Charité — Universitätsmedizin Berlin, Schuhmannstr. 20/21, 10117, Berlin, Germany

    Andreas Ströhle

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Ströhle, A. (2005). New Pharmacological Treatment Approaches for Anxiety Disorders. In: Holsboer, F., Ströhle, A. (eds) Anxiety and Anxiolytic Drugs. Handbook of Experimental Pharmacology, vol 169. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-28082-0_18

Download citation

Publish with us

Policies and ethics

Search

Navigation