scholarly journals Anticonvulsant property of N-salicyloyltryptamine: evidence of enhance of central GABAergic neurotransmission

2009 ◽  
Vol 15 (4) ◽  
pp. 165-168 ◽  
Author(s):  
Lucindo J. Quintans-Júnior ◽  
Davi A. Silva ◽  
Jullyana S. Siqueira ◽  
Adriano A.S. Araújo ◽  
Adriana G. Guimarães ◽  
...  

AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40% of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABA A-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.

1976 ◽  
Vol 72 (7) ◽  
pp. 763-794 ◽  
Author(s):  
Takashi YAJIMA ◽  
Katsuko URITANI ◽  
Rie AOKI ◽  
Tsutomu SUZUKI ◽  
Keiji NAKAMURA

Author(s):  
G. Oswell ◽  
M.A. Kaunisto ◽  
M. Kallela ◽  
E. Hämäläinen ◽  
V. Anttila ◽  
...  

2008 ◽  
Vol 27 (11) ◽  
pp. 811-818 ◽  
Author(s):  
GJ Amabeoku

Aqueous and methanol leaf extracts of Nylandtia spinosa L. Dumont (Polygalaceae) were evaluated for anticonvulsant activity against tonic seizures produced in mice by pentylenetetrazole (PTZ), bicuculline, picrotoxin, and N-methyl-DL-aspartic acid (NMDLA). Aqueous leaf extract of N. spinosa (50–400 mg/kg, i.p.) and methanol extract (50–400 mg/kg, i.p.) significantly attenuated PTZ (95 mg/kg, i.p.)-induced tonic seizures. Doses of 400 mg/kg (i.p.) and 100–400 mg/kg (i.p.) of aqueous extract of N. spinosa significantly delayed the onset of tonic seizures elicited by bicuculline (35 mg/kg, i.p.) and picrotoxin (12 mg/kg, i.p.), respectively. Methanol extract (200–400 mg/kg, i.p.) and (50–400 mg/kg, i.p.) significantly delayed the onset of tonic seizures induced by bicuculline (35 mg/kg, i.p.) and picrotoxin (12 mg/kg, i.p.), respectively, whereas 400 mg/kg (i.p.) significantly reduced the incidence of picrotoxin (12 mg/kg, i.p.)-induced seizures. Both aqueous and methanol leaf extracts of N. spinosa did not affect NMDLA (400 mg/kg, i.p.)-induced tonic seizures. Phenobarbitone (12.5 mg/kg, i.p.) and diazepam (0.5 mg/kg, i.p.) antagonized tonic seizures induced by PTZ (95 mg/kg, i.p.), bicuculline (35 mg/kg, i.p.), and picrotoxin (12 mg/kg, i.p.) but did not affect NMDLA (400 mg/kg, i.p.)-induced seizures. Phenytoin (30 mg/kg, i.p.) did not alter the tonic seizures produced by either PTZ (95 mg/kg, i.p.), bicuculline –2-(35 mg/kg, i.p.), or picrotoxin (12 mg/kg, i.p.). The results obtained indicate that both aqueous and methanol leaf extracts of N. spinosa possess anticonvulsant property, thus justifying the use of the plant by traditional medicine practitioners in the treatment of epilepsy. The relatively high LD50 of greater than 3600 mg/kg (p.o.) and 1780 mg/kg (i.p.) obtained with the aqueous extract suggest that the plant is relatively safe in mice. The phytochemical analysis carried out showed the presence of tannins, saponins, reducing sugars, alkaloids, flavonoids, triterpene steroids, and cardiac glycosides in the plant material.


2004 ◽  
Vol 1 (1) ◽  
pp. 91-99
Author(s):  
Georges Chapouthier ◽  
Patrice Venault

2021 ◽  
Vol 14 ◽  
Author(s):  
Taavi Vanaveski ◽  
Svetlana Molchanova ◽  
Dan Duc Pham ◽  
Annika Schäfer ◽  
Ceren Pajanoja ◽  
...  

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1α expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of γ-aminobutyric acid (GABA) type A receptor-α2 subunit (GABARα2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1α in neurons. Along with this, GABARα2 expression was enhanced in the hippocampus of the PGC-1α Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABARα2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1α Tg mice compared with controls. To study whether drugs acting on PPARγ can affect GABARα2, we employed pioglitazone that elevated GABARα2 expression in primary cultured neurons. Similar results were obtained using the specific PPARγ agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1α regulates GABARα2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABARα2 expression via the PPARγ/PGC-1α system.


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