Skip to main content
SpringerLink
Log in

Differences Between Cerebrovascular and Anti-Ischemic Effects of Dopamine, Docosahexaenoyldopamine, and GABA–Docosahexaenoyldopamine Conjugate

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

The cerebrovascular and anti-ischemic effects of dopamine and synthetic docosahexaenoyldopamine (DHA-DA) and the GABA–DHA-DA conjugate (OXL1220) were compared and found to differ. Dopamine and DHA-DA increased blood flow in intact and ischemic brain that was associated with pronounced hypertensive reactions. The latter inhibited dopamine transporter with IC50 = 29 μM but was practically inactive as a ligand for dopamine receptors. OXL1220 produced a selective vasodilating effect on blood flow in brain subjected to transient global ischemia. Only OXL1220 competed in vitro for specific binding sites of [3H]-gabazine in rat-brain GABAA-receptors. Therefore, conjugation of a neuromediator (GABA) to the DHA-DA changed the dopaminergic activity of the compound to GABA-ergic with respect to vascular tone in ischemic brain.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. R. S. Mirzoyan, T. S. Gan’shina, D. V. Maslennikov, et al., BioMed Res. Int., 2014, Article ID 586501 (2014), 8 pp.; http://dx.doi.org/10.1155/2014/586501.

  2. N. Itokazu, Y. Ikegaya, M. Nishikawa, and N. Matsuki, Brain Res., 862, 211 – 216 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. S. Chalon, S. Vancassel, L. Zimmer, et al., Lipids, 36(9), 937 – 944 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Y. Yu, Y.Wu, C. Patch, et al., J. Nutr. Biochem., 24, 1349 – 1358 (2013).

  5. R. A. M. Haast and A. J. Kiliaan, Prostaglandins Leukotrienes Essent. Fatty Acids, 92, 3 – 14 (2015); http://dx.doi.org/10.1016/j.plefa.2014.01.002.

  6. R. S. Mirzoyan, T. S. Gan’shina, A. V. Gnezdilova, et al., Eksp. Klin. Farmakol., 78(1), 16 – 20 (2015).

    CAS  Google Scholar 

  7. M. G. Akimov and V. V. Bezuglov, N-Acylated Dopamines: A New Life for the Old Dopamine. Dopamine: Functions, Regulation and Health Effects, E. Kudo and Y. Fujii (eds.), Nova Publ., New York (2012); ISBN: 978 – 1 – 61942 – 147 – 9, Chap. 2, pp. 49 – 80.

  8. V. Bezuglov, M. Bobrov, N. Gretskaya, et al., Bioorg. Med. Chem. Lett., 11, 447 – 449 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. A. V. Topchyan, M. G. Balasanyan, T. S. Gan’shina, and R. S. Mirzoyan, Eksp. Klin. Farmakol., 62, No. 6, 29 – 31 (1999).

    CAS  Google Scholar 

  10. R. S. Mirzoyan, M. B. Plotnikov, T. S. Gan’shina, et al., Handbook for Preclinical Drug Trials [in Russian], Part 1, Grif i K, Moscow (2012), pp. 480 – 487.

  11. Y. Ito, T. Koshiba, M. Doi, et al., Synapse, 10, No. 4, 326 – 333 (1992).

    Article  CAS  PubMed  Google Scholar 

  12. J. Hawkinson, M. Acosta-Burruel, C. Kimbrough, et al., Eur. J. Pharmacol., 304(1 – 3), 141 – 146 (1996).

  13. G. I. Kovalev, D. A. Abaimov, M. V. Voronin, et al., Neirokhimiya, 24(2), 150 – 156 (2007).

    Google Scholar 

  14. S. P. H. Alexander, A. Mathie, and J. A. Peters, Br. J. Pharmacol., 147(3), S32, S86 (2006).

  15. Y. I. Chen, J. Ren, F. N. Wang, et al., Neurosci. Lett., 431, 231 – 235 (2008).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. C. O. Tan, J. Neurophysiol., 101(6), 2738 – 2740 (2009); DOI: 10.1152/jn.00141.2009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. T. Esaki, Y. Itoh, K. Shimoji, et al., J. Pharmacol. Exp. Ther., 303(2), 497 – 502 (2002); DOI: 10.1121/jpet.102.039081.

    Article  CAS  PubMed  Google Scholar 

  18. J.-K. Choi, Y. I. Chen, E. Hamel, and B. G. Jenkins, Neuro-Image, 30, 700 – 712 (2006).

    PubMed  Google Scholar 

  19. C. A. Gleason, R. Robinson, A. P. Harris, et al., J. Appl. Physiol., 92(2), 717 – 724 (2002); DOI: 10.1152/japplphysiol.00600.2001.

    Article  CAS  PubMed  Google Scholar 

  20. T. Kawano, K. Tsutsumi, H. Miyake, and K. Mori, Stroke, 19, 1540 – 1543 (1988).

    Article  CAS  PubMed  Google Scholar 

  21. C. C. Toner, K. Connelly, R. Whelpton, et al., Br. J. Anaesth., 86(4), 550 – 554 (2001); DOI: 10.1093/bja/86.4.550.

    Article  CAS  PubMed  Google Scholar 

  22. M. Y.-T. Globus, R. Busto, E. Martinez, et al., J. Neurochem., 57, 470 – 478 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. M. Y.-T. Globus, M. D. Ginsberg, and R. Busto, Neurosci. Lett., 127, 39 – 42 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. F. Filloux and J. Townsend, Exp. Neurol., 119, 79 – 88 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. K. W. Lange, W. D. Rausch, W. Gsell, et al., J. Neural Transm., [Suppl] 43, 183 – 201 (1994).

  26. M. A. Caldwell, J. M. Reymann, D. Bentue-Ferrer, et al., Neuropsychobiology, 34, 117 – 124 (1996).

    Article  CAS  PubMed  Google Scholar 

  27. W. Stillwell and S. R. Wassal, Chem. Phys. Lipids, 126, 1 – 27 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. P. H. Andersen, Eur. J. Pharmacol., 166(3), 493 – 504 (1989).

    Article  CAS  PubMed  Google Scholar 

  29. A. V. Gorbunova, T. S. Gan’shina, N. M. Gretskaya, et al., Eksp. Klin. Farmakol., 76(8), 13 – 16 (2013).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Zakusov Institute of Pharmacology, Baltiiskaya Ul. 8, Moscow, 125315, Russia

    R. S. Mirzoyan, T. S. Gan’shina, A. V. Topchyan, N. A. Khailov, I. N. Kurdyumov, G. I. Kovalev, I. A. Zimin, Yu. Yu. Firstova & E. V. Vasil’eva

  2. Shemyakin—Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia

    N. M. Gretskaya & V. V. Bezuglov

Authors
  1. R. S. Mirzoyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. S. Gan’shina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Topchyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. A. Khailov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. N. Kurdyumov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. I. Kovalev
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. A. Zimin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu. Yu. Firstova
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. V. Vasil’eva
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N. M. Gretskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. V. V. Bezuglov
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 49, No. 10, pp. 19 – 24, October, 2015.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mirzoyan, R.S., Gan’shina, T.S., Topchyan, A.V. et al. Differences Between Cerebrovascular and Anti-Ischemic Effects of Dopamine, Docosahexaenoyldopamine, and GABA–Docosahexaenoyldopamine Conjugate. Pharm Chem J 49, 661–666 (2016). https://doi.org/10.1007/s11094-016-1348-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-016-1348-7

Keywords

Search

Navigation