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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2003; 49(1): 23-27


Action of a phenazepam metabolite, 2-amino-5-bromo-2'-chlorobenzophenone, onglycine and nmda receptors of rat hippocampal pyramidal neurones

M. V. Kopanitsa

    Ін-т фізіології ім. О. О. Богомольця НАН України, Київ


Abstract

Action of 2-amino-5-bromo-2'-chlorobenzophenone (ABPH), a metabolite of phenazepam, on currents evoked by the activation of glycine and glutamate NMDA receptors has been investigated in enzymatically isolated hippocampal rat pyramidal neurones. It is demonstrated that 3 - 10 μM ABPH caused an inhibitory effect on glycine receptors which was more prominent after pre-incubation with the drug. Peak amplitude of NMDA receptor-mediated currents was weakly potentiated after prolonged (4-6 min) incubation with 10 μM ABPH. Thus, the effects of the benzophenone metabolites should be taken into account when analysing the action of phenazepam and other benzodiazepine drugs.

References

  1. Андронати С.А., Авруцкий А.В., Богатский А.В., и др. Феназепам – К.: Наук. думка, 1982. – 288 с.
  2. Врублевский С.В., Валеев А.Е., Черневская Н.И. Метод быстрой смены тестирующих растворов при исследованиях изолированных клеток // Физиол. журн. – 1985. – 31, № 2. – С. 241 – 242.
  3. Копаниця М.В., Руденко О.П. Похідні N-заміщених 2-аміно-5-галогенбензофенонів прискорюють де- сенситизацію ГАМК-активованих струмів в ізо- льованих нейронах Пуркін’є щурів // Арх. клін. експерим. медицины. – 2002. – 11, № 1. – С. 22 – 25.
  4. Bond A.J., Hailey D.M., Lader M.H. Plasma concentrations of benzodiazepines // Br. J. Clin. Pharmacol. –1977. – 4, № 1. – P. 51 – 56.
  5. Kondratskaya E.L., Lishko P.V., Chatterjee S.S., Krishtal O.A. BN52021, a platelet activating factor antagonist, is a selective blocker of glycine-gated chloride channel // Neurochem. Int. – 2002. – 40, № 7. – P. 647 – 653.
  6. Kopanitsa M.V., Lambert, J.J. Modulation of GABAA receptors by 5-bromobenzophenone derivatives depends on the presence of ?-subunit. In: Abstr. 2nd Bogomoletz-Nencki Symposium «Intracellular Signalling in Excitable Cells»,1-3 September Kyiv. – 2002. – P. 9.
  7. Kopanitsa M.V., Yakubovska L.M., Rudenko O.P., Krishtal O.A. Modulation of GABAА receptor-mediated currents by benzophenone derivatives in isolated rat Purkinjeneurones // Neuropharmacology. – 2002. – 43, № 4. –P. 764 – 777.
  8. Kopanitsa M.V., Zhuk O.V., Zinkovsky V.G., Krishtal O.A. Modulation of GABAA receptor-mediated currents by phenazepam and its metabolites // Naunyn-Schmiede- bergs Arch. Pharmacol. – 2001. – 364 , № 1. – P. 1 – 8.
  9. 9. Olfson M., Pincus H.A. Use of benzodiazepines in the community // Arch. Intern. Med. – 1994. – 154, № 11. – P. 1235 – 1240.
  10. 10. Olivier H., Fitz-Gerald M.J., Babiak B. Benzodiazepines revisited // J. La. State. Med. Soc. – 1998. – 150, № 10. – P. 483 – 485.
  11. Olsen R.W., Tobin A.J. Molecular biology of GABAA receptors // FASEB J. – 1990. – 4, № 5. – P. 1469 – 1480.
  12. Turner D.M., Sapp D.W., Olsen R.W. The benzodiazepine/alcohol antagonist Ro 15-4513: binding to a GABAAreceptor subtype that is insensitive to diazepam // J. Phar-macol. Exp. Ther. – 1991. – 257, № 3. – P. 1236 – 1242.

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