RESUMEN
OBJECTIVE: To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models. METHODS: The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison. RESULTS: Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P < 0.050-0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model. CONCLUSIONS: In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Química Encefálica , Encéfalo/efectos de los fármacos , Lobelia/química , Lobelina/administración & dosificación , Convulsiones/tratamiento farmacológico , Ácido gamma-Aminobutírico/análisis , Animales , Anticonvulsivantes/aislamiento & purificación , Convulsivantes/administración & dosificación , Modelos Animales de Enfermedad , Lobelina/aislamiento & purificación , Masculino , Ratones , Pentilenotetrazol/administración & dosificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Convulsiones/inducido químicamenteRESUMEN
The complete chiral separation of methoxamine and lobeline was achieved by capillary zone electrophoresis on an ethylbenzene-deactivated fused-silica capillary column and with cyclodextrins (CDs) as buffer additives. Among the CDs investigated in this study, i.e. alpha-CD, beta-CD, dimethyl-beta-CD, hydroxypropyl-beta-CD and gamma-CD, all the three beta-type CDs showed chiral recognition on the two drugs investigated. Under the investigated conditions, the baseline chiral separation of methoxamine can be achieved with 90 mM Tris-H3PO4 (pH 2.5) containing 11.5 mM of the three beta-type CDs, with dimethyl-beta-CD giving the best resolution, whereas the baseline chiral separation of lobeline can be realized by using 90 mM Tris-H3PO4 buffer (pH 2.5) containing 5.8 mM dimethyl-beta-CD or 29.5 mM hydroxypropyl-beta-CD.
Asunto(s)
Ciclodextrinas/química , Lobelina/aislamiento & purificación , Metoxamina/aislamiento & purificación , Derivados del Benceno/química , Tampones (Química) , Electroforesis Capilar/instrumentación , Electroforesis Capilar/métodos , Indicadores y Reactivos , EstereoisomerismoRESUMEN
Five cyclodextrin derivatives, namely phosphate ester beta-CD, carboxymethyl-beta-CD(CM-beta-CD), bis-[6-oxygen-(beta-carboxymethyl-succinic acid-4-ester)] beta-CD(F-CM-beta-CD), beta-CD polymer(P-beta-CD), carboxymethyl-poly-beta-CD (CD-P-beta-CD), were used as chiral selector for separation of three basic drugs, lobeline, thiopendonesodium, flunarizine by capillary zone electrophoresis (CZE). All the five cyclodextrins have chiral separation ability to lobeline. P-beta-CD and CM-P-beta-CD have chiral recognition to thiopentonesodium and flunarizine. The results indicate that via optimizing separation conditions by varying pH and the concentration of chiral selectors the three racemic drugs could be baseline separated with 2% P-beta-CD or 0.5% CM-P-beta-CD in the buffer of 30 mmol/L Tris-H3PO4. And the best resolution ranging from 4 to 35 with CM-P-beta-CD as chiral additive was obtained within 10 min. The results were much better than those reported in other references.
Asunto(s)
Ciclodextrinas , Electroforesis Capilar/instrumentación , Flunarizina/aislamiento & purificación , Lobelina/aislamiento & purificación , beta-Ciclodextrinas , Electroforesis Capilar/métodos , Estereoisomerismo , Tiopental/aislamiento & purificaciónRESUMEN
Three chiral selectors CM-beta-CD, EP-beta-CD, beta-CD were studied for the enatio-separation of three drugs under optimum conditions respectively. The results demonstrate that the resolving power for the drugs is as follows CM-beta-CD > EP-beta-CD > beta-CD, with the exception of lobeline. This is due to the--CH2COOCH3 group of CM-beta-CD, which will change the combination and improve the recognition on guest molecules. Although EP-beta-CD is inferior to CM-beta-CD for the separation of chlorpheniramine and verapamil, it has excellent recognition on lobeline and it has not been reported previously. In most cases EP-beta-CD is superior to beta-CD. The explanations are: (1) EP-beta-CD has good solubility in water, which enables high concentrations to be used and consequently achieves excellant separation of racemic compounds, (2) the polymerization of beta-CD changes the properties of CD units and the process produces a more rigid and different conformation from CD, (3) we must attribute much merits to the cooperation or synergism of two, three or even more CD moieties of two polymers for inclusion. Complexation with analytes possesses more than one guest part in their structure.