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Prospects for Intranasal Delivery of Neuropeptides to the Brain

  • K. V. ShevchenkoEmail author
  • I. Yu. Nagaev
  • L. A. Andreeva
  • V. P. Shevchenko
  • N. F. Myasoedov
MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION
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Intranasal administration (INA) of medicines has the advantages of being noninvasive, painless, simple, and convenient. The basic approaches to solving problems with effective delivery of peptides to the brain through nasal membranes are discussed with respect to nasal cavity anatomy and physiology. INA can bypass the blood—brain barrier although proteolysis of the peptides by olfactory epithelium components, i.e., the enzyme barrier, is an obstacle. Pro-Gly-Pro, Pro-Gly-Pro-Leu, Semax, and Selank were used as reference peptides for in vivo experiments. The maximum contents in rat blood plasma of Pro-Gly-Pro-Leu, Semax, Pro-Gly-Pro, and Selank were 0.54, 1.69, 1.30, and 1.04%, respectively, of the administered amount of labeled peptide. The corresponding values in rat brain for Pro-Gly-Pro-Leu, Semax, Pro-Gly-Pro, and Selank reached 0.0013, 0.13, 0.04, and 0.16%. The methionine in Semax was replaced by alanine, glycine, threonine, and tryptophan to minimize its proteolysis during transversal of the enzyme barrier. Liposomes and acetylation of the N-terminal amino acids were also used to improve the stability of Semax. Use of N-acetyl-Semax was shown to be most promising. In vitro experiments used leucine aminopeptidase (incubation medium contained 12.6% Semax after 60 min), dipeptidyl peptidase (95.4%), carboxypeptidases B (96.8%) and Y(51.0%), nasal mucus enzymes (4.0%), and microsomal fractions of rat brain (9.0%) and blood plasma (0.7%). Proteolysis of Semax formed mainly His-Phe-Pro-Gly-Pro, Phe-Pro-Gly-Pro, and Pro-Gly-Pro.

Keywords

intranasal administration enzyme barrier peptide proteolysis 

Notes

Acknowledgments

The work was partially sponsored by the RAS Presidium Basic Research Programs “Basic research for development of biomedical technologies” and “Molecular and cellular biology and post-genomic technologies.”

References

  1. 1.
    E. V. Radchenko, P. V. Karpov, S. B. Sosnin, et al., in: Proceedings of the XXth Mendeleev Convention on General and Applied Chemistry [in Russian], Ekaterinburg, 2016, p. 432.Google Scholar
  2. 2.
    A. S. Dyabina, E. V. Radchenko, V. A. Palyulin, and N. S. Zefirov, Dokl. Akad. Nauk, 470(6), 720 – 723 (2016).Google Scholar
  3. 3.
    T. Furubayashi, A. Kamaguchi, K. Kawaharada, et al., Biol. Pharm. Bull., 30(5), 1007 – 1010 (2007).CrossRefPubMedGoogle Scholar
  4. 4.
    R. Hashizume, T. Ozawa, S. M. Gryaznov, et al., Neuro-Oncology, 10(2), 112 – 120 (2008).CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    D-D. Kim, in: Absorption Studies: In situ, In vitro and In silico Models, C. Ehrhardt and K-J. Kim (eds.), Springer, USA, 2008, pp. 216 – 234.CrossRefGoogle Scholar
  6. 6.
    K. R. Jadhav, M. N. Gambhire, I. M. Shaikh, et al., Curr. Drug Ther., 2(1), 27 – 38 (2007).CrossRefGoogle Scholar
  7. 7.
    Y. Xie,W. Lu, S. Cao, et al., Chem. Pharm. Bull., 54(1), 48 – 53 (2006).CrossRefPubMedGoogle Scholar
  8. 8.
    H. R. Costantino, L. Illum, G. Brandt, et al., Int. J. Pharm., 337(1 – 2), 1 – 24 (2007).CrossRefPubMedGoogle Scholar
  9. 9.
    A. H. Elshafeey, E. R. Bendas, and O. H. Mohamed, AAPS PharmSciTech, 10(2), 361 – 367 (2009).CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    S. Z. Piskunov, Vestn. Otorinolaringol., No. 2, 19 – 22 (1999).Google Scholar
  11. 11.
    S. V. Dhuria, L. R. Hanson, and W. H. Frey II, J. Pharm. Sci., 99(4), 1654 – 1673 (2010).CrossRefPubMedGoogle Scholar
  12. 12.
    M. A. Sarkar, Pharm. Res., 9(1), 1 – 9 (1992).CrossRefPubMedGoogle Scholar
  13. 13.
    Y. C. Wong and Z. Zuo, Pharm. Res., 27(7), 1208 – 1223 (2010).CrossRefPubMedGoogle Scholar
  14. 14.
    L. R. Hanson and W. H. Frey II, BMC Neurosci., 9 (Suppl 3), S5 (2008).CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    N. J. Johnson, L. R. Hanson, and W. H. Frey, Mol. Pharm., 7(3), 884 – 893 (2010).CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    M. M. Migliore, T. K. Vyas, R. B. Campbell, et al., J. Pharm. Sci., 99(4), 1745 – 1761 (2010).CrossRefPubMedGoogle Scholar
  17. 17.
    M. M. Wen, Discov. Med., 11(61), 497 – 503 (2011).PubMedGoogle Scholar
  18. 18.
    B. J. Balin, R. D. Broadwell, M. Salcman, and M. el-Kalliny, J. Comp. Neurol., 251(2), 260 – 280 (1986).CrossRefPubMedGoogle Scholar
  19. 19.
    R. Draghia, C. Caillaud, R. Manicom, et al., Gene Ther., 2(6), 418 – 423 (1995).PubMedGoogle Scholar
  20. 20.
    R. G. Thorne, G. J. Pronk, V. Padmanabhan, and W. H. Frey II, Neuroscience, 127(2), 481 – 496 (2004).CrossRefPubMedGoogle Scholar
  21. 21.
    M. Yamada, T. Chiba, J. Sasabe, et al., Neuropsychopharmacology, 33(8), 2020 – 2032 (2008).CrossRefPubMedGoogle Scholar
  22. 22.
    N. Nonaka, S. A. Farr, H. Kageyama, et al., J. Pharmacol. Exp. Ther., 325(2), 513 – 519 (2008).CrossRefPubMedGoogle Scholar
  23. 23.
    S. V. Dhuria, L. R. Hanson, and W. H. Frey, J. Pharmacol. Exp. Ther., 328(1), 312 – 320 (2009).CrossRefPubMedGoogle Scholar
  24. 24.
    N. Mygind, Nasal Allergy, Blackwell Scientific Publications, Oxford. 1979, pp. 3 – 333.Google Scholar
  25. 25.
    D. F. Proctor and Ib H. P. Anderson, The Nose: Upper Airway Physiology and the Atmospheric Environment, Elsevier / North-Holland Biomedical Press, Amsterdam, 1982, pp. 1 – 464.Google Scholar
  26. 26.
    J. P. Schreider, “Comparative anatomy and function of the nasal passages,” in: Toxicology of the Nasal Passages, C. S. Barrow (ed.), Hemisphere, Washington, DC, 1986, pp. 1 – 25.Google Scholar
  27. 27.
    V. H. L. Lee and A. Yamamoto, Adv. Drug Deliv. Rev., 4(2), 171 – 207 (1989).CrossRefGoogle Scholar
  28. 28.
    S. D. Kashi, R. M. Patel, E. Hayakawa, et al., in: Proc. 14th Int. Symp. Control. Rel. Bioact. Mater., Abstr. No. 13 (1987).Google Scholar
  29. 29.
    R. E. Stratford and V. H. L. Lee, Int. J. Pharm., 30(1), 73 – 82 (1986).CrossRefGoogle Scholar
  30. 30.
    S. D. Kashi and V. H. Lee, Life Sci., 38(22), 2019 – 2028 (1986).CrossRefPubMedGoogle Scholar
  31. 31.
    V. H. Lee, Crit. Rev. Ther. Drug Carrier Syst., 5(2), 69 – 97 (1988).PubMedGoogle Scholar
  32. 32.
    A. B. Shenvi, Biochemistry, 25(6), 1286 – 1291 (1986).CrossRefPubMedGoogle Scholar
  33. 33.
    R. Bone, A. B. Shenvi, C. A. Kettner, and D. A. Agard, Biochemistry, 26(24), 7609 – 7614 (1987).CrossRefPubMedGoogle Scholar
  34. 34.
    A. Hussain, J. Faraj, Y. Aramaki, and J. E. Truelove, Biochem. Biophys. Res. Commun., 133(3), 923 – 928 (1985).CrossRefPubMedGoogle Scholar
  35. 35.
    J. March, Advanced Organic Chemistry: Reactions, Mechanisms, and Structures, McGraw-Hill Book Company, New York, 1968.Google Scholar
  36. 36.
    K. S. E. Su, in: Proc. Am. Pharm. Assoc., Acad. Pharm. Sci. Basic Symp., San Francisco, 1986, 16:17.Google Scholar
  37. 37.
    H. R. Mahler and E. H. Cordes, Biological Chemistry, Harper & Row Publishers, New York, 1971, pp. 99 – 101.Google Scholar
  38. 38.
    T. Ohwaki, H. Ando, S. Watanabe, and Y. Miyake, J. Pharm. Sci., 74(5), 550 – 552 (1985).CrossRefPubMedGoogle Scholar
  39. 39.
    S. Hirai, T. Ikenaga, and T. Matswzawa, Diabetes, 27(3), 296 – 299 (1978).CrossRefGoogle Scholar
  40. 40.
    T. Mizutani, J. Pharm. Sci., 70(5), 493 – 496 (1981).CrossRefPubMedGoogle Scholar
  41. 41.
    J. Ogino, K. Noguchi, and K. Terato, Chem. Pharm. Bull. (Tokyo), 27(12), 3160 – 3163 (1979).CrossRefGoogle Scholar
  42. 42.
    S. T. Anik and J.-Y. Hwang, Int. J. Pharm., 16(2), 181 – 190 (1983).CrossRefGoogle Scholar
  43. 43.
    D. B. Butler and A. C. Ivy, Arch. Otolaryngol., 39(2), 109 – 123 (1944).CrossRefGoogle Scholar
  44. 44.
    J. G. Hardy, S. W. Lee, and C. G. Wilson, J. Pharm. Pharmacol., 37(5), 294 – 297 (1985).CrossRefPubMedGoogle Scholar
  45. 45.
    F. Y. Aoki and J. C. Crowley, Br. J. Clin. Pharmacol., 3(5), 869 – 878 (1976).CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    A. S. Harris, M. Ohlin, S. Lethagen, and I. M. Nilsson, J. Pharm. Sci., 77(4), 337 – 339 (1988).CrossRefPubMedGoogle Scholar
  47. 47.
    K. S. E. Su and K. M. Campanale, in: Transnasal Systemic Medications: Fundamentals, Developmental Concepts and Biomedical Assessments, Y. W. Chien (ed.), Elsevier Scientific Publishing Co., Inc., New York, 1985, pp. 139 – 160.Google Scholar
  48. 48.
    S. P. Newman, Inhal. Ther., 76, 194 – 196 (1984).Google Scholar
  49. 49.
    L. Silverman, C. E. Billings, and M. W. First, Particle Size Analysis in Industrial Hygiene, Academic Press, New York, 1971.Google Scholar
  50. 50.
    A. A. Hussain, S. Hirai, and R. Bawarshi, J. Pharm. Sci., 68, 1141 – 1144 (1980).Google Scholar
  51. 51.
    K. S. Su, K. M. Campanale, and C. L. Gires, J. Pharm. Sci., 73(9), 1251 – 1254 (1984).CrossRefPubMedGoogle Scholar
  52. 52.
    S. Hirai, T. Yashiki, T. Matsuzawa, and H. Mima, Int. J. Pharm., 7(4), 317 – 325 (1981).CrossRefGoogle Scholar
  53. 53.
    C. E. Vaca, M. Conradi, M. Sievertzon, and J. Bergman, Chem.-Biol. Interact., 93(3), 235 – 249 (1994).CrossRefPubMedGoogle Scholar
  54. 54.
    H. Inoue, H. Iguchi, A. Kono, and Y. Tsuruta, J. Chromatogr. B: Biomed. Sci. Appl., 724(2), 221 – 230 (1999).CrossRefGoogle Scholar
  55. 55.
    Z. Chen, J. Wu, G. B. Baker, et al., J. Chromatogr. A., 914(1 – 2), 293 – 298 (2001).CrossRefPubMedGoogle Scholar
  56. 56.
    E. J. Miller, A. J. Narkates, and M. A. Niemann, Anal. Biochem., 190(1), 92 – 97 (1990).CrossRefPubMedGoogle Scholar
  57. 57.
    F. Hernandez, C. Hidalgo, and J. V. Sancho, J. AOAC Int., 83(3), 728 – 734 (2000).PubMedGoogle Scholar
  58. 58.
    R. Box, P. Woolley, and C. Pon, Eur. J. Biochem., 116(1), 93 – 99 (1981).CrossRefPubMedGoogle Scholar
  59. 59.
    H. Miyano, T. Toyo’oka, K. Imai, and T. Nakajima, Anal. Biochem., 150(1), 125 – 130 (1985).CrossRefPubMedGoogle Scholar
  60. 60.
    M. Sandberg, H. Hagberg, I. Jacobson, et al., Life Sci., 41(7), 829 – 832 (1987).CrossRefPubMedGoogle Scholar
  61. 61.
    T. Herraiz, V. Casal, and M. C. Polo, Z. Lebensm.-Unters. Forsch., 199(4), 265 – 269 (1994).CrossRefPubMedGoogle Scholar
  62. 62.
    A. L. Ronnberg, C. Hansson, T. Drakenberg, and R. Hakanson, Anal. Biochem., 139(2), 329 – 337 (1984).CrossRefPubMedGoogle Scholar
  63. 63.
    M. H. Joseph and P. Davies, J. Chromatogr., 277, 125 – 136 (1983).CrossRefPubMedGoogle Scholar
  64. 64.
    R. F. Chen, C. Scott, and E. Trepman, Biochim. Biophys. Acta., 576(2), 440 – 455 (1979).CrossRefPubMedGoogle Scholar
  65. 65.
    K. S. Lee and D. G. Drescher, J. Biol. Chem., 254(14), 6248 – 6251 (1979).PubMedGoogle Scholar
  66. 66.
    Y. Ohkura, M. Kai, and H. Notha, J. Chromatogr. B: Biomed. Sci. Appl., 659(1 – 2), 85 – 107 (1994).CrossRefGoogle Scholar
  67. 67.
    M. Kato, T. Fukushima, T. Santa, et al., Biomed. Chromatogr., 9(4), 193 – 194 (1995).CrossRefPubMedGoogle Scholar
  68. 68.
    T. Hiratsuka, J. Biol. Chem., 261(16), 7294 – 7299 (1986).PubMedGoogle Scholar
  69. 69.
    H. Inoue, K. Moritani, Y. Date, et al., Analyst, 120(4), 1141 – 1145 (1995).CrossRefPubMedGoogle Scholar
  70. 70.
    M. J. Treuheit and T. L. Kirley, Anal. Biochem., 212(1), 138 – 142 (1993).CrossRefPubMedGoogle Scholar
  71. 71.
    I. Daskalakis, M. D. Lucock, A. Anderson, et al., Biomed. Chromatogr., 10(5), 205 – 212 (1996).CrossRefPubMedGoogle Scholar
  72. 72.
    T. Sueyoshi, T. Miyata, S. Iwanaga, et al., J. Biochem. (Tokyo, Jpn.), 97(6), 1811 – 1813 (1985).CrossRefGoogle Scholar
  73. 73.
    J. Tuls, L. Geren, J. D. Lambeth, and F. Millett, J. Biol. Chem., 262(21), 10020 – 10025 (1987).PubMedGoogle Scholar
  74. 74.
    R. J. Kok, J. Visser, F. Moolenaar, et al., J. Chromatogr. B: Biomed. Sci. Appl., 693(1), 181 – 189 (1997).CrossRefGoogle Scholar
  75. 75.
    H. Meguro, J. H. Kim, C. Bai, et al., Chirality, 13(8), 441 – 445 (2001).CrossRefPubMedGoogle Scholar
  76. 76.
    H. Yoshida, Y. Nakano, K. Koiso, et al., Anal. Sci., 17(1), 107 – 112 (2001).CrossRefPubMedGoogle Scholar
  77. 77.
    K. M. De Antonis, P. R. Brown, and S. A. Cohen, Anal. Biochem., 223(2), 191 – 197 (1994).CrossRefPubMedGoogle Scholar
  78. 78.
    S. A. Cohen and D. P. Michaud, Anal. Biochem., 211(2), 279 – 287 (1993).CrossRefPubMedGoogle Scholar
  79. 79.
    B. De Foresta, Le. T. Nguyen, C. Nicot, and A. Alfsen, Biochimie, 61(4), 523 – 533 (1979).CrossRefPubMedGoogle Scholar
  80. 80.
    T. Honda, M. G. Cacace, A. Sada, and M. Tokushige, J. Chromatogr., 371, 353 – 360 (1986).CrossRefPubMedGoogle Scholar
  81. 81.
    K. Nakashima, T. Ishimaru, N. Kuroda, and S. Akiyama, Biomed. Chromatogr., 9(2), 90 – 93 (1995).CrossRefPubMedGoogle Scholar
  82. 82.
    M. Wada, S. Kinoshita, Y. Itayama, et al., J. Chromatogr. B: Biomed. Sci. Appl., 721(2), 179 – 186 (1999).CrossRefGoogle Scholar
  83. 83.
    H. Nohta, T. Yukizawa, Y. Ohkura, et al., Anal. Chim. Acta., 344(3), 233 – 240 (1997).CrossRefGoogle Scholar
  84. 84.
    H. Kanazawa, T. Nagatsuka, M. Miyazaki, and Y. Matsushima, J. Chromatogr. A, 763(1 – 2), 23 – 29 (1997).CrossRefPubMedGoogle Scholar
  85. 85.
    R. R. Hudgins, F. Huang, G. Gramlich, and W. M. Nau, J. Am. Chem. Soc., 124(4), 556 – 564 (2002).CrossRefPubMedGoogle Scholar
  86. 86.
    P. Langguth, H. Spahn, and H. P. Merkle, J. Chromatogr., 528(1), 55 – 64 (1990).CrossRefPubMedGoogle Scholar
  87. 87.
    A. Neidle, M. Banay-Schwartz, S. Sacks, and D. S. Dunlop, Anal. Biochem., 180(2), 291 – 297 (1989).CrossRefPubMedGoogle Scholar
  88. 88.
    D. Jin, K. Nagakura, S. Murofushi, et al., J. Chromatogr. A, 822(2), 215 – 224 (1998).CrossRefPubMedGoogle Scholar
  89. 89.
    A. Tsugita, M. Kamo, C. S. Jone, and N. Shikama, J. Biochem. (Tokyo, Jpn.), 106(1), 60 – 65 (1989).CrossRefGoogle Scholar
  90. 90.
    R. D. Coleman, T. W. Kim, A. M. Gotto Jr., and C. Y. Yang, Biochim. Biophys. Acta., 1037(1), 129 – 132 (1990).CrossRefPubMedGoogle Scholar
  91. 91.
    Y. Huang, H. Matsunaga, A. Toriba, et al., Anal. Biochem., 270(2), 257 – 267 (1999).CrossRefPubMedGoogle Scholar
  92. 92.
    A. Toriba, K. Adzuma, T. Santa, and K. Imai, Anal. Chem., 72(4), 732 – 739 (2000).CrossRefPubMedGoogle Scholar
  93. 93.
    N. Zaman, M. Varsanyi, L. M. Heilmeyer Jr., et al., Eur. J. Biochem., 182(3), 577 – 584 (1989).CrossRefPubMedGoogle Scholar
  94. 94.
    J. S. Mills, H. M. Miettinen, D. Barnidge, et al., J. Biol. Chem., 273(17), 10428 – 10435 (1998).CrossRefPubMedGoogle Scholar
  95. 95.
    J. I. Clark and D. Garland, J. Cell Biol., 76(3), 619 – 627 (1978).CrossRefPubMedGoogle Scholar
  96. 96.
    V. K. Boppana, C. Miller-Stein, J. F. Politowski, and G. R. Rhodes, J. Chromatogr., 548(1 – 2), 319 – 327 (1991).CrossRefPubMedGoogle Scholar
  97. 97.
    W. Zhan, T. Wang, and S. F. Li, Electrophoresis, 21(17), 3593 – 3599 (2000).CrossRefPubMedGoogle Scholar
  98. 98.
    H. Wang, J. Li, T. X. Yang, and H. S. Zhang, J. Chromatogr. Sci., 39(9), 365 – 369 (2001).CrossRefPubMedGoogle Scholar
  99. 99.
    T. Toyo’oka, N. Tomoi, T. Oe, and T. Miyahara, Anal. Biochem., 276(1), 48 – 58 (1999).CrossRefPubMedGoogle Scholar
  100. 100.
    T. Toyo’oka, D. Jin, N. Tomoi, et al., Biomed. Chromatogr., 15(1), 56 – 67 (2001).CrossRefPubMedGoogle Scholar
  101. 101.
    C. Ferrandiz, E. Perez-Paya, L. Braco, and C. Abad, Biochem. Biophys. Res. Commun., 203(1), 359 – 365 (1994).CrossRefPubMedGoogle Scholar
  102. 102.
    M. Kai, A. Nakashima, and Y. Ohkura, J. Chromatogr. B: Biomed. Sci. Appl., 688(2), 205 – 212 (1997).CrossRefGoogle Scholar
  103. 103.
    M. Kai and Y. Ohkura, Anal. Chim. Acta, 182, 177 – 183 (1986).CrossRefGoogle Scholar
  104. 104.
    E. Kojima, M. Kai, and Y. Ohkura, Anal. Chim. Acta, 248(1), 213 – 217 (1991).CrossRefGoogle Scholar
  105. 105.
    M. Kai, E. Kojima, Y. Ohkura, and M. Iwasaki, J. Chromatogr. A, 653(2), 235 – 240 (1993).CrossRefPubMedGoogle Scholar
  106. 106.
    I. Yu. Nagaev, V. P. Shevchenko, V. V. Podval’nyuk, et al., Radiokhimiya, 44(1), 65 – 71 (2002).Google Scholar
  107. 107.
    C. Tomboly, R. Dixit, I. Lengyel, et al., J. Labelled Compd. Radiopharm., 44(5), 355 – 363 (2001).CrossRefGoogle Scholar
  108. 108.
    D. A. Zaitsev, Yu. A. Zolotarev, and N. F. Myasoedov, Dokl. Akad. Nauk, 313(3), 619 – 622 (1990).Google Scholar
  109. 109.
    N. F. Myasoedov, J. Labelled Compd. Radiopharm., 50(9 – 10), 831 – 847 (2007).CrossRefGoogle Scholar
  110. 110.
    Yu. A. Zolotarev, A. K. Dadayan, B. V. Vas’kovskii, et al., Bioorg. Khim., 26(7), 512 – 515 (2000).PubMedGoogle Scholar
  111. 111.
    Yu. A. Zolotarev, A. K. Dadayan, O. V. Dolotov, et al., Bioorg. Khim., 32(2), 183 – 191 (2006).PubMedGoogle Scholar
  112. 112.
    K. V. Shevchenko, I. Yu. Nagaev, L. Yu. Alfeeva, et al., Bioorg. Khim., 32(1), 64 – 70 (2006).PubMedGoogle Scholar
  113. 113.
    V. N. Potaman, L. V. Antonova, V. A. Dubynin, et al., Neurosci. Lett., 127(1), 133 – 136 (1991).CrossRefPubMedGoogle Scholar
  114. 114.
    K. V. Shevchenko, T. V. V’yunova, L. A. Andreeva, et al., Khim.-farm. Zh., 49(2), 12 – 17 (2015); Pharm. Chem. J., 49(2), 82 – 87 (2015).Google Scholar
  115. 115.
    K. V. Shevchenko, T. V. V’yunova L. A. Andreeva, et al., Byull. Eksp. Biol. Med., 158(7), 43 – 48 (2014).Google Scholar
  116. 116.
    K. V. Shevchenko, T. V. V’yunova, L. A. Andreeva, et al., Dokl. Akad. Nauk, 456(5), 613 – 617 (2014).Google Scholar
  117. 117.
    K. V. Shevchenko, T. V. V’yunova, L. A. Andreeva, et al., in: Abstracts of the VIth Russian Symposium “Proteins and Peptides” [in Russian], Ufa, 2013, p. 173.Google Scholar
  118. 118.
    N. N. Karkishchenko, V. V. Khoron’ko, S. A. Sergeeva, and V. N. Karkishchenko, Pharmacokinetics [in Russian], Feniks (Hippocrates Series), Rostov, 2001.Google Scholar
  119. 119.
    S. T. Charlton, J. Whetstone, S. T. Fayinka, et al., Pharm. Res., 25(7), 1531 – 1543 (2008).CrossRefPubMedGoogle Scholar
  120. 120.
    A. Albert, Nature, 182(4633), 421 – 422 (1958).CrossRefPubMedGoogle Scholar
  121. 121.
    M. A. Hussain, A. B. Shenvi, S. M. Rowe, and E. Shefter, Pharm. Res., 6(2), 186 – 189 (1989).CrossRefPubMedGoogle Scholar
  122. 122.
    K. V. Shevchenko, T. V. V’yunova, L. A. Andreeva, and N. F. Myasoedov, in: Abstracts of the VIth Russian Symposium “Proteins and Peptides” [in Russian], Ufa, 2013, p. 172.Google Scholar
  123. 123.
    K. V. Shevchenko, T. V. V’yunova, I. Yu. Nagaev, et al., Bioorg. Khim., 39(3), 320 – 325 (2013).PubMedGoogle Scholar
  124. 124.
    I. P. Ashmarin, V. N. Nezavibat’ko, N. F. Myasoedov, et al., Zh. Vyssh. Nervn. Deyat., 47(2), 420 – 430 (1997).Google Scholar
  125. 125.
    S. B. Seredenin, M. M. Kozlovskaya, Yu. A. Blednov, et al., Zh. Vyssh. Nervn. Deyat., 48(1), 153 – 160 (1998).Google Scholar
  126. 126.
    N. V. Kost, O. Yu. Sokolov, M. V. Gabaeva, et al., Bioorg. Khim., 27(3), 180 – 183 (2001).PubMedGoogle Scholar
  127. 127.
    A. A. Zozulya, V. K. Meshavkin, A. V. Toropov, et al., Byull. Eksp. Biol. Med., 127(2), 211 – 214 (1999).CrossRefGoogle Scholar
  128. 128.
    O. Yu. Sokolov, V. K. Meshavkin, N. V. Kost, and A. A. Zozulya, Byull. Eksp. Biol. Med., 133(2), 158 – 161 (2002).CrossRefGoogle Scholar
  129. 129.
    N. F. Myasoedov, D. L. Rochev, L. A. Lyapina, et al., Dokl. Akad. Nauk, 453(4), 457 – 460 (2013).Google Scholar
  130. 130.
    K. V. Shevchenko, T. V. V’yunova, I. Yu. Nagaev, et al., Bioorg. Khim., 37(4), 475 – 482 (2011).PubMedGoogle Scholar
  131. 131.
    K. V. Shevchenko, I. Yu. Nagaev, L. A. Andreeva, et al., Dokl. Akad. Nauk, 450(2), 245 – 247 (2013).Google Scholar
  132. 132.
    K. V. Shevchenko, A. P. Khrapko, V. I. Shvets, and N. F. Myasoedov, Dokl. Akad. Nauk, 429(4), 554 – 557 (2009).Google Scholar
  133. 133.
    A. Brioschi, F. Zenga, G. P. Zara, et al., Neurol. Res., 29(3), 324 – 330 (2007).CrossRefPubMedGoogle Scholar
  134. 134.
    B. McCormack and G. Gregoriadis, Biochim. Biophys. Acta, 1291(3), 237 – 244 (1996).CrossRefPubMedGoogle Scholar
  135. 135.
    J. Zhu, J. Xue, Z. Guo, and R. E. Marchant, Colloids Surf., B, 58(2), 242 – 249 (2007).CrossRefGoogle Scholar
  136. 136.
    A. D. Sangadzhieva, Z. V. Bakaeva, G. E. Samonina, et al., Vestn. Mosk. Univ., Ser. 16. Biol., No. 2, 7 – 11 (2013).Google Scholar
  137. 137.
    K. V. Shevchenko, I. Yu. Nagaev, L. A. Andreeva, et al., Dokl. Akad. Nauk, 449(6), 733 – 735 (2013).Google Scholar
  138. 138.
    M. Bradbury, The Concept of a Blood Brain Barrier, John Wiley & Sons, Chichester, New York, Brisbane, Toronto, 1979.Google Scholar
  139. 139.
    A. J. Kastin and W. Pan, “Brain Influx of Endogenous Peptides Affecting Food Intake,” in: Blood-Spinal Cord and Brain Barriers in Health and Disease, H. S. Sharma and J. Westman (eds.), Amsterdam, 2004, pp. 57 – 62.Google Scholar
  140. 140.
    B. V. Zlokovic, M. B. Segal, H. Davson, et al., Endocrinol. Exp., 24(1 – 2), 9 – 17 (1990).PubMedGoogle Scholar
  141. 141.
    W. A. Banks and A. J. Kastin, Am. J. Physiol., 259(1), 1 – 10 (1990).CrossRefGoogle Scholar
  142. 142.
    T. O. Price, W. K. Samson, M. L. Niehoff, and W. A. Banks, Peptides, 28(12), 2372 – 2381 (2007).CrossRefPubMedGoogle Scholar
  143. 143.
    W. Pan, H. Tu, and A. J. Kastin, Peptides, 27(4), 911 – 916 (2006).CrossRefPubMedGoogle Scholar
  144. 144.
    A. J. Kastin, V. Akerstrom, and W. Pan, Peptides, 21(12), 1811 – 1817 (2000).CrossRefPubMedGoogle Scholar
  145. 145.
    W. Pan and A. J. Kastin, Prog. Neurobiol., 84(2), 148 – 156 (2008).CrossRefPubMedGoogle Scholar
  146. 146.
    A. J. Kastin and V. Akerstrom, Neuroendocrinology, 75(6), 367 – 374 (2002).CrossRefPubMedGoogle Scholar
  147. 147.
    W. A. Banks, A. J. Kastin, W. Huang, et al., Peptides, 17(2), 305 – 311 (1996).CrossRefPubMedGoogle Scholar
  148. 148.
    W. A. Banks, D. Uchida, A. Arimura, et al., Ann. N. Y. Acad. Sci., 805, 270 – 277 (1996).CrossRefPubMedGoogle Scholar
  149. 149.
    D. Dogrukol-Ak, F. Tore, and N. Tuncel, Curr. Pharm. Des., 10(12), 1325 – 1340 (2004).CrossRefPubMedGoogle Scholar
  150. 150.
    A. Urayama, S. Yamada, R. Kimura, et al., Life Sci., 72(4 – 5), 601 – 607 (2002).CrossRefPubMedGoogle Scholar
  151. 151.
    A. Urayama, S. Yamada, Y. Ohmori, et al., Drug Metab. Pharmacokinet., 18(5), 310 – 318 (2003).CrossRefPubMedGoogle Scholar
  152. 152.
    W. A. Banks, J. B. Jaspan, W. Huang, and A. J. Kastin, Peptides, 18(9), 1423 – 1429 (1997).CrossRefPubMedGoogle Scholar
  153. 153.
    V. Ganapathy and S. Miyauchi, AAPS J., 7, No. 4, E852-E856 (2005).CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    M. Fry and A. V. Ferguson, Int. J. Pept., 2010, Art. ID 616757 (2010); DOI: 10.1155 / 2010 / 616757.Google Scholar
  155. 155.
    D. T. O’Hagan, H. Critchley, N. F. Farraj, et al., Pharm. Sci., 7(7), 772 – 776 (1990).Google Scholar
  156. 156.
    D-W. Lee, S. A. Shirley, R. F. Lockey, and S. S. Mohapatra, Respir. Res., 7(112) (2006); DOI: 10.1186 / 1465–9921–7-112.Google Scholar
  157. 157.
    G. Di Colo, Y. Zambito, and C. Zaino, J. Pharm. Sci., 97(5), 1652 – 1680 (2008).CrossRefPubMedGoogle Scholar
  158. 158.
    G. N. Kopylova, B. A. Umarova, G. E. Samonina, et al., in: Proceedings of the 1 st Convention of CIS Physiologists [in Russian], Dagomys, Sochi, 2005, Vol. 2, p. 237.Google Scholar
  159. 159.
    D. J. Prockop, H. R. Keiser, and N. A. Sjoerdsma, Lancet, 2(7255), 527 – 528 (1962).CrossRefPubMedGoogle Scholar
  160. 160.
    M. E. Raichle, A. M. MacLeod, A. Z. Snyder, et al., Proc. Natl. Acad. Sci. USA., 98(2), 676 – 682 (2001).CrossRefPubMedGoogle Scholar
  161. 161.
    M. D. Greicius and V. Menon, J. Cogn. Neurosci., 16(9), 1484 – 1492 (2004).CrossRefPubMedGoogle Scholar
  162. 162.
    I. S. Lebedeva, Ya. R. Panikratova, O. Yu. Sokolov, et al., in: Proceedings of the Vth Convention of Russian Pharmacologists “Scientific Bases for New Drug Discovery and Design” [in Russian], Yaroslavl, 2018, p. 140.Google Scholar
  163. 163.
    D. M. Clerico, W. C. To, and D. C. Lanza, “Anatomy of the human nasal passages,” in: Handbook of Olfaction and Gustation, R. L. Doty (ed.), Marcel Dekker, Inc., New York, 2003, pp. 1 – 16.Google Scholar
  164. 164.
    L. B. Buck, “Smell and taste: The chemical senses,” in: Principles of Neural Science, E. R. Kandel, J. H. Schwartz, and T. M. Jessell (eds.), McGraw-Hill, New York, 2000, pp. 625 – 652.Google Scholar
  165. 165.
    H. Baker and R. F. Spencer, Exp. Brain. Res., 63(3), 461 – 473 (1986).CrossRefPubMedGoogle Scholar
  166. 166.
    R. D. Broadwell and B. J. Balin, J. Comp. Neurol., 242(4), 632 – 650 (1985).CrossRefPubMedGoogle Scholar
  167. 167.
    K. Kristensson and Y. Olsson, Acta Neuropathol. (Berl.), 19(2), 145 – 154 (1971).CrossRefGoogle Scholar
  168. 168.
    A. Mackay-Sim, J. St. John, and J. E. Schwob, “Neurogenesis in the adult olfactory epithelium,” in: Handbook of Olfaction and Gustation, R. L. Doty (ed.), Marcel Dekker, Inc., New York, 2003, pp. 93 – 113.Google Scholar
  169. 169.
    C. L. Graff and G. M. Pollack, Pharm. Res., 20(8), 1225 – 1230 (2003).CrossRefPubMedGoogle Scholar
  170. 170.
    P. Hussar, N. Tserentsoodol, H. Koyama, et al., Chem. Senses, 27(1), 7 – 11(2002).CrossRefPubMedGoogle Scholar
  171. 171.
    K. K. Kandimalla and M. D. Donovan, Pharm. Res., 22(7), 1121 – 1128 (2005).CrossRefPubMedGoogle Scholar
  172. 172.
    F. Miragall, D. Krause, U. de Vries, and R. Dermietzel, J. Comp. Neurol., 341(4), 433 – 448 (1994).CrossRefPubMedGoogle Scholar
  173. 173.
    K. Takano, T. Kojima, M. Go, et al., J. Histochem. Cytochem., 53(5), 611 – 619 (2005).CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • K. V. Shevchenko
    • 1
    Email author
  • I. Yu. Nagaev
    • 1
  • L. A. Andreeva
    • 1
  • V. P. Shevchenko
    • 1
  • N. F. Myasoedov
    • 1
  1. 1.Institute of Molecular Genetics, Russian Academy of Sciences (IMG RAS)MoscowRussia

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