Skip to main content
SpringerLink
Log in

Antiamnesic properties of analogs and mimetics of the tripeptide human urocortin 3

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Amnesia is a deficit in memory caused by brain damage, disease, or trauma. Until now, there are no successful medications on the drug market available to treat amnesia. Short analogs and mimetics of human urocortin 3 (Ucn 3) tripeptide were synthetized and tested for their action against amnesia induced by eletroconvulsion in mice. Among the 16 investigated derivatives of Ucn 3 tripeptide, eight compounds displayed antiamnesic effect. Our results proved that the configuration of chiral center of glutamine does not affect the antiamnesic properties. Alkyl amide or isoleucyl amide at the C-terminus may lead to antiamnesic compounds. As concerned the N-terminus, acetyl, Boc, and alkyl ureido moieties were found among the active analogs, but the free amino function at the N-terminus usually led to an inactive derivatives. These observations may lead to the design and synthesis of small peptidomimetics and amino acid derivatives as antiamnesic drug candidates, although the elucidation of the mechanism of the action requires further investigations.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ader R, Weijnen JAWM, Moleman P (1972) Retention of a passive avoidance response as a function of the intensity and duration of electric shock. Psychosom Sci 26:126–128

    Google Scholar 

  • Al-Ozairi A, McCullagh S, Feinstein A (2014) Prediction posttraumatic stress symptoms following mild, moderate, and severe traumatic brain injury: The role of posttraumatic amnesia. J Head Trauma Rehab. doi:10.1097/HTR.0000000000000043 (May 8 Epub)

    Google Scholar 

  • Andrade C, Thyagarajan S, Singh NM, Vinod PS (2008) Sanjay Kumar Rao N, Chandra JS. Celoxib as an in vivo probe of cyclooxygenase-2 mechanisms underlying retrograde amnesia in an animal model of ECT. J Neural Transm 115:1063–1070

    Article  CAS  PubMed  Google Scholar 

  • Andrade C, Shaikh SA, Narayan L, Bissey C, Belanoff J (2012) Admimistration of a selective glucocorticoid antagonist attenuates electroconvulsive shock-induced retrograde amnesia. J Neural Transm 119:337–344

    Article  CAS  PubMed  Google Scholar 

  • Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Bidzseranova A, Penke B, Tóth G, Telegdy G (1991) The effects of atrial natriuretic peptides on electroconvulsive shock-induced amnesia in rats. Transmitter-mediated action. Neuropeptides 19:102–106

    Article  Google Scholar 

  • Bidzseranova A, Varga J, Telegdy G (1993) The effects of brain natriuretic peptide-32 on electroconvulsive shock–induced amnesia in rats. Eur J Pharmacol 232:305–308

    Article  CAS  PubMed  Google Scholar 

  • Chalmers DT, Lovenberg TW, Grigoriadis DE, Behan DP, De Souza EB (1996) Corticotrophin-releasing factor receptors: from molecular biology to drug design. Trends Pharmacol Sci 17(4):166–172

    Article  CAS  PubMed  Google Scholar 

  • DeWitt DS, Perez-Polo R, Hulsebosch CE, Dash PK, Robertson CS (2013) Challenges in the development of rodent models of mild traumatic brain injury. J Neurotrauma 30:688–701

    Article  PubMed  Google Scholar 

  • Gregory-Roberts EM, Naismith SL, Cullen KM, Hickie IB (2010) Electroconvulsive therapy-induced persistent retrograde amnesia:could it be minimised by ketamine or other pharmacological approaches? J Affect Disord 125:39–45

    Article  Google Scholar 

  • Griebel G, Holsboer F (2012) Neuropeptide receptor ligands as drugs for psychiatric diseases: the end of the beginning? Nat Rev Drug Discov 11(6):462–478

    Article  CAS  PubMed  Google Scholar 

  • Janssen D, Kozicz T (2013) Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health. Front Endocrinol (Lausanne) 4:28. doi:10.3389/fendo

    Google Scholar 

  • Kovács A, Telegdy G (1994) CGRP prevents elecroconvulsive shock-induced amesia in rats. Pharmacol Biochem Behav 47:121–125

    Article  PubMed  Google Scholar 

  • Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C et al (2001) Identification of urocortin III, an additional member of the corticotrophin-releasing factor(CRF) family with high affinity for CRF2 receptor. Proc Natl Acad Sci USA 98:7570–7575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Louto TM, Iverson GL, Losoi H, Waljas M, Tenovuo O, Kataja A et al (2015) Clinical correlates of retrograde amnesia in mild traumatic brain injury. Brain Injury 29:565–572

    Article  Google Scholar 

  • Luo J, Min S, Wei K, Li P, Dong J, Liu YF (2011) Propofol protects against impairment of learning-memory and imbalance of hippocampal Glu/GABA induced by elecroconvulsive shock in depressed rats. J Anesth 25:657–665

    Article  PubMed  Google Scholar 

  • Meeter M, Murre JM, Janssen SM, Birkenhager T, van den Broek WW (2011) Retrograde amnesia after electroconvulsive therapy: a temporary effect? J Affect Disord 132:216–222

    Article  PubMed  Google Scholar 

  • Nielsen RM, Olse KS, Lauritsen AO, Boesen HC (2014) Electroconvulsive therapy as a treatment for protracted refractory delirium in the intensive care unit—five cases and a review. J Crit Care 29:881

    Article  PubMed  Google Scholar 

  • Rákosi K, Masaru T, Zarándi M, Telegdy G, Tóth GK (2014) Short analogs and mimetics of human urocortin 3 display antidepressant effects in vivo. Peptides 62:59–66

    Article  PubMed  Google Scholar 

  • Rao SK, Andrade C, Reddy K, Nadappa KN, Thyagarajan S, Chandra S (2002) Memory protective effect of indomethacin against electroconvulsive shock-induced retrograde amnesia in rats. Biol Psychiatry 51:770–773

    Article  CAS  PubMed  Google Scholar 

  • Read J, Bentall R (2010) The effectiveness of electroconvulsive therapy: a literature review. Epidermiol Psychiatr Soc 19:333–347

    Article  Google Scholar 

  • Reul JM, Holsboer F (2002) Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. Curr Opin Pharmacol 2(1):23–33

    Article  CAS  PubMed  Google Scholar 

  • Spitz G, Ponsford JL, Rudzki D, Maller JJ (2012) Association between cognitive performance and functional outcome following traumatic brain injury: a longitudinal multilevel examination. Neuropsychology 26:604–612

    Article  PubMed  Google Scholar 

  • Sushma M, Susha S, Guido S (2004) Pre-electroconvulsive shock administration of calcium channel blockers reduced retrograde amnesia induced by ECS. Indian J Exp Biol 42:1141–1144

    CAS  PubMed  Google Scholar 

  • Tanaka M, Telegdy G (2008) Antidepressant-like effects of the CRH family peptides urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice. Brain Res Bull 75:509–512

    Article  CAS  PubMed  Google Scholar 

  • Tanaka M, Kádár K, Tóth G, Telegdy G (2011) Antidepressant-like effects of urocortin 3 fragments. Brain Res Bull 84:414–418

    Article  CAS  PubMed  Google Scholar 

  • Telegdy G, Adamik A (2008) Involvement of CRH receptors in urocortin-induced hyperthermia. Peptides 29:1937–1942

    Article  CAS  PubMed  Google Scholar 

  • Telegdy G, Bidzseranova A, Kovács A, Gabos L (1992) Antiamnestic properties of some neuropeptides and the involvement of neurotransmitters in the rats. Patol Fiziol Eksp Ter 4:75–77

    PubMed  Google Scholar 

  • Telegdy G, Tiricz H, Adamik A (2005) Involvement of neurotransmitters in urocortin-induced passive avoidance learning in mice. Brain Res Bull 67:242–247

    Article  CAS  PubMed  Google Scholar 

  • Telegdy G, Adamik A, Tóth G (2006) The action of urocortins on body temperature in rats. Peptides 27:2268–2294

    Article  Google Scholar 

  • Telegdy G, Kádár K, Tóth G (2011) Anxiolytic action of urocortin 3 fragments in mice. Behav Brain Res 222:295–298

    Article  CAS  PubMed  Google Scholar 

  • Telegdy G, Foris L, Jászberényi M (2014) Urocortin 3 impairs fear-motivated learning in mice. Transmitter mediation. Behavior Brain Res 270:326–329

    Article  CAS  Google Scholar 

  • Valdez GR, Sabino V, Koob GF (2004) Increased anxiety-like behavior and ethanol-self-administration in dependent rats: reversal via corticotrophin-releasing factor-2 receptor activation. Alcohol Clin Exp Res 29:865–872

    Article  Google Scholar 

  • Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S et al (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotrophin-releasing factor. Nature 378:287–292

    Article  CAS  PubMed  Google Scholar 

  • Vécsei L, Bollok I, Penke B, Telegdy G (1986) Somatostatin and (D-Trp8, D-Cys14)-somatostatin delay extinction and reverse electroconvulsive shock-induced amnesia in rats. Psychoneuroendocrinol 11:111–115

    Article  Google Scholar 

  • Walker WC, Ketchum JM, Marwitz JH, Chen J, Hammond F, Sherer M et al (2010) A multicentre study on clinical utility of post-traumatic amnesia duration in predicting global outcome after moderate-severe traumatic brain injury. J Neurol Neurosurg Psychiatry 81:87–89

    Article  CAS  PubMed  Google Scholar 

  • Waters RP, Rivalan M, Bangasser DA, Deussing JM, Ising M, Wood SK, Holsboer F, Summers CH (2015) Evidence for the role of corticotropin-releasing factor in major depressive disorder. Neurosci Biobehav Rev 58:63–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the Hungarian Brain Research Program through Grant Nos. KTIA.13. NAP-A-III/8 and TÁMOP 4.2.2A-11/1/KONV-2012-0052.

Author information

Authors and Affiliations

  1. Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary

    Anita Kármen Kovács, Kinga Rákosi, Márta Zarándi & Gábor K. Tóth

  2. Department of Pathophysiology, University of Szeged, Semmelweis u. 1, Szeged, 6725, Hungary

    Gyula Telegdy

  3. MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences, University of Szeged, Semmelweis u. 1, Szeged, 6725, Hungary

    Gyula Telegdy

Authors
  1. Gyula Telegdy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anita Kármen Kovács
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kinga Rákosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Márta Zarándi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gábor K. Tóth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gábor K. Tóth.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Telegdy, G., Kovács, A.K., Rákosi, K. et al. Antiamnesic properties of analogs and mimetics of the tripeptide human urocortin 3. Amino Acids 48, 2261–2266 (2016). https://doi.org/10.1007/s00726-016-2268-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-016-2268-2

Keywords

Search

Navigation