Advertisement

Synthesis and Pharmacological Activity of 2-(Diethylamino)Ethyl 9-Hydroxy-9H-Fluorene-9-Carboxylate Hydrochloride

  • L. K. KhnychenkoEmail author
  • E. E. Yakovleva
Article
  • 2 Downloads

New fluorenecarboxylic acid derivatives (structural analogs of amizil) were synthesized. A compound with low toxicity (LD50 = 45 ± 9.9 mg/kg) and antidepressant and antianxiety effects was identified. The central and peripheral muscarinic anticholinergic properties of 2-dimethylaminoethyl 9-hydroxyfluorene-9-carboxylate were studied using an arecoline tremor model. Apharmacological analysis showed that the new amizil structural analog exhibited pronounced central muscarinic anticholinergic activity and did not possess peripheral muscarinic anticholinergic effects. The advantages of the tested compound over amizil, amitriptyline that is widely used in the clinic, and the benzodiazepine tranquilizer diazepam were discussed. The results indicated that 2-diethylaminoethyl 9-hydroxyfluorene-9-carboxylate was promising for further development for the treatment of depressive and anxiety disorders.

Keywords

cholinergic system amizil structural analogs antidepressants amitriptyline 

References

  1. 1.
    M. D. Mashkovskii, Drugs [in Russian], Novaya Volna, Moscow (2014).Google Scholar
  2. 2.
    E. Castren and T. Rantamaki, Dev. Neurobiol., 70(5), 289 – 297 (2010).CrossRefGoogle Scholar
  3. 3.
    P. J. Fitzgerald, Med. Hypotheses, 80(6), 823 – 826 (2013).CrossRefGoogle Scholar
  4. 4.
    A. A. Crawford, S. Lewis, D. Nutt, et al., Psychopharmacology (Berlin), 231(15), 2921 – 2931 (2014).CrossRefGoogle Scholar
  5. 5.
    N. A. Losev, E. E. Yakovleva, et al., RU Pat. No. 2,535,027, Feb 20, 2014; Byull. Izobret., No. 34 (2014).Google Scholar
  6. 6.
    N. A. Losev, N. S. Sapronov, L. K. Khnychenko, and P. D. Shabanov, Pharmacology of New Cholinergic Agents (Pharmacology – Clinic) [in Russian], Art-ekspress, St. Petersburg (2015).Google Scholar
  7. 7.
    R. R. Burtner and J. W. Cusic, J. Am. Chem. Soc., 65(8), 1582 – 1585 (1943).CrossRefGoogle Scholar
  8. 8.
    Ministry of Health of the RF Order No. 267 dated June 19 “On the protection of animals from abuse,” Moscow (2003).Google Scholar
  9. 9.
    A. N. Mironov and N. D. Bunyatyan, Handbook for Preclinical Drug Trials [in Russian], Parts 1 – 2, Grif i K, Moscow (2012).Google Scholar
  10. 10.
    V. P. Fisenko (ed.), Handbook for Experimental (Preclinical) Studies of New Drugs [in Russian], IIA Remedium CSC, Moscow (2000), pp. 131 – 137.Google Scholar
  11. 11.
    V. B. Pozorovskii, Psikhofarmakol. Biol. Narkol., 7(3 – 4), 2090 – 2120 (2007).Google Scholar
  12. 12.
    S. S. Krylov, Farmakol. Toksikol., 19(3), 21 – 25 (1956).Google Scholar
  13. 13.
    S. S. Krylov, G. A. Livanov, A. N. Petrov, et al., Clinical Toxicology of Drugs. Cholinotropic Agents [in Russian], Lan', St. Petersburg (1999).Google Scholar
  14. 14.
    S. V. Anichkov, Selective Action of Mediators [in Russian], Meditsina, Leningrad (1974).Google Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Institute of Experimental MedicineSt. PetersburgRussia

Personalised recommendations