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View at the anticonvulsive and Nootropic effects from position of new imagination on understanding of the structure and function GABA-Benzodiazepine receptor complex on the basis of the investigation of the molecular geometry and quantumchemical characteristics main group anticonvulsants, inhibitor amino acids and some convulsive agent
6th International Conference on Brain Disorders and Therapeutics
July 01-02, 2019 | Paris, France
George N Shilau and Oleg N Bubel
Republican Clinic Medical Center, Belarus Belorussian State University, Belarus
Keynote : J Brain Neurol
Abstract:
Statement of the Problem: Until these days, searching
of endogen agonists of benzodiazepine receptors is
actual task, because a lot of problems clinical medicine
neurology, Epileptology, Narcology deepened the
understanding mechanism of action and function of
GABA benzodiazepine receptor complex to elaborate new
perspective anticonvulsive and nootropic compounds.
Purpose: Investigate quantum mechanics characteristics
and molecular geometry has three conformational states
GABA: linear (GABA-1 conformer), bucket-like (GABA-3
conformer) agonists of which is bucket-like conformer of
GABA and isoguvacine, but antagonists are picrotoxin and
bicuculline; cyclic (GABA-2 conformer) agonists of which
are cyclic conformer of GABA, glycine and β-alanine,but
antagonists are bemegride, pentilentetrazol and
strychnine; and GABA-3 receptors; maine anticonvulsant’s
groups. Investigate nootropic’s and anticonvulsants effects
one-valence salts of glycine and GABA.
Method: Molecular geometry of the benzodiazepine’s
pharmacophores, main GABA conformers and glycine where
studied in the approximation of molecular mechanics with
the use of the MM2 force field. Influence introperitonial
injection different one-valence salts of glycine and GABA
on the cerebral neurophisiological activity in white rats
(taking of EEG) and their anticonvulsant activity using
strychnine, picrotoxin, pentylenetetrazol and maximal
electro seizure models.
Results: It was show, that anticonvulsive and other
behavioral effects of derivatives of barbituric acid,
benzazepine, benzodiazepine, gidantoine, succinimide and
oxasolidindione are realized probably via GABA-2 receptors
to switch on them the following functional centers of their
structure are nessesary: α, and [δ-ε] for barbitirates; β, [δ-
ε] and γ for carbamazepine; β and [δ-ε] for benzodiazepine
derivatives, gabapentine and vigabatrine; α, β, γ and [δ-ε]
for gidantoine and oxasolidindione derivatives; α, β, γ for
succinimide derivatives. The expression of any (including
nootropic) behavioral effects of anticonvulsants and
inhibitory amino acids depends on power, location and
numbers of hydrogen bounds developed between active
centers of pharmacophore of anticonvulsant or inhibitory
amino acids and active centers of functional skeleton of
GABA-2 receptorcomplex.
Conclusion: 1. The more stronger the charge on the atoms
of the pharmacophore of the GABA agonist, the more
expressive its anticonvulsant effect and Vice versa, the
weaker the charge on the atoms, the more expressive
the nootropic effects appear 2. There are perspectives of
synthesis of compounds, pharmacophore of which should
be like as cyclic conformer of GABA, glycine and β-alanine
on their quantum mechanics characteristics and molecular
geometry.
Biography:
George N Shilau has completed his PhD at age of 29 years old from Byelorussian State Medical University. He long time work as senior scientific worker in the laboratory of the biochemistry of neurohormones and neurosurgery over mention University and then as leading scientific worker central scientific-investigating laboratory of Byelorussian Medical Postgraduate Academia and neurologist practitioner, and also as MRY diagnostician. Then he worked as deputy Director of the center of Medical Information “EOCEN” and continues his scientific work in close cooperation with Laboratory of free-radical process chemistry of the Research Institute of Physical Chemical Problems of the Belarusian State University. Now he works as MRY diagnostician of the Republican Clinic Medical Center of the Presidential Administration. He has published more than 40 papers in reputed journals. His interests include neuropharmacology (GABAbenzodiazepine and glycine receptors and their interactions), the clinic of epilepsy.
E-mail: george_shilau@mail.ru
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