THESIS
2013
xi, 51 p. : ill. ; 30 cm
Abstract
Classical benzodiazepines are the most frequently prescribed drugs acting on the central
nervous system (CNS). They exert their therapeutic effects via binding to the
benzodiazepine-site of the type A γ-aminobutyric acid (GABA
A) receptors, which changes
the channel opening frequency. The positive modulation of BZ causes behavioral effects such
as anxiolysis, sedation, myorelaxation and amnesia and these effects could be governed by
the different subtypes of GABA
A receptor. Formula A, a dried decoction of four herbal
constituents including Flos Albiziae (F), Caulis Polygoni Multiflori (C), Rhizoma Corydalis
Yanhusuo (R) and Radix Bupleuri (B), was documented as an anxiolytic. However, no detail
studies with regards to its effectiveness, the possible dispensability of its constitu...[
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Classical benzodiazepines are the most frequently prescribed drugs acting on the central
nervous system (CNS). They exert their therapeutic effects via binding to the
benzodiazepine-site of the type A γ-aminobutyric acid (GABA
A) receptors, which changes
the channel opening frequency. The positive modulation of BZ causes behavioral effects such
as anxiolysis, sedation, myorelaxation and amnesia and these effects could be governed by
the different subtypes of GABA
A receptor. Formula A, a dried decoction of four herbal
constituents including Flos Albiziae (F), Caulis Polygoni Multiflori (C), Rhizoma Corydalis
Yanhusuo (R) and Radix Bupleuri (B), was documented as an anxiolytic. However, no detail
studies with regards to its effectiveness, the possible dispensability of its constituents and
possible synergism and antagonism of its anxiolytic effect were performed. In this thesis,
dissection and analysis of the decoction of Formula A for its behavioral effects in vivo and in
vitro experiments were done. For in vivo experiment, elevated plus maze, holeboard, rotatod,
passive avoidance test were done to profile its anxiolytic, sedative, myorelaxant and amnesia
respectively. While in vitro experiment of radio-ligand binding assay and whole-cell patch
clamp will be carried out to show its interaction with possible binding sites. In the results,
extracts of F and C had shown mutual antagonism in their anxiolytic effect while extract FRB
was able to induce an enhanced anxiolytic-like effect with heavy sedation. Both extract FCB
and Formula A induced an additive anxiolytic-like effect without other detectable
accompanying effects. However, Formula A could induce a higher degree of anxiolytic effect
as compared to extract FCB. In electrophysiological experiment, Formula A and the mono-extracts
C, R and B were shown to induce hyperpolarization in rat cortical neurons; in
addition, Formula A and extract C-induced currents could be enhanced by co-administration
of diazepam.
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