RESUMO
Valeriana wallichii DC (Valerianaceae), popularly named as Indian valerian has been shown to exist as three chemotypes. The present study evaluated the antidepressant like effect of root essential oil of Valeriana wallichii patchouli alcohol chemotype in both acute and chronic treatment study using forced swim test (FST). Mice (n=6 per group) received 10, 20 and 40 mg/kg p.o. doses of test drug. Single administration of oil significantly inhibited the immobility period (57.6% and 46.9%) at doses 20 and 40 mg/kg respectively without changing the motor function (p<0.05). Similarly, daily administration of essential oil (20mg/kg) for 14 days significantly reduced the immobility period (69.9%) in FST (p<0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (29%) and serotonin (19%) (p<0.05) was found at 20mg/kg dose, while no change was observed at 10 and 40 mg/kg doses. The antidepressant-like effect of essential oil (20mg/kg) was prevented by pretreatment of mice with l-arginine (750 mg/kg i.p.) and sildenafil (5mg/kg i.p). On the contrary, pretreatment of mice with l-NAME (10mg/kg i.p.) or methylene blue (10mg/kg i.p.) potentiated the antidepressant action of essential oil (10mg/kg). Taken together, these findings demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.
Assuntos
Antidepressivos/farmacologia , Óxido Nítrico/metabolismo , Óleos Voláteis/farmacologia , Transdução de Sinais , Valeriana/química , Animais , Antidepressivos/química , Arginina/farmacologia , Encéfalo/metabolismo , Avaliação de Medicamentos , Teste de Esforço/efeitos dos fármacos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Resposta de Imobilidade Tônica/efeitos dos fármacos , Azul de Metileno/farmacologia , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Norepinefrina/metabolismo , Óleos Voláteis/administração & dosagem , Óleos Voláteis/química , Piperazinas/farmacologia , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Raízes de Plantas/química , Purinas/farmacologia , Serotonina/metabolismo , Citrato de Sildenafila , Sulfonas/farmacologia , Natação , Testes de Toxicidade AgudaRESUMO
An economical new process has been developed for the synthesis of donepezil hydrochloride (1) an anti-Alzheimer's drug. The process involves Darzen reaction of pyridine-4-carboxaldehyde and 2-bromo-5,6-dimethoxy indanone affording epoxide 5,6-dimethoxy-3-(pyridine-4-yl)spiro[indene-2,2'-oxiran]-1(3H)-one (4) as a key intermediate. The one-pot deoxygenation of 4 and hydrogenation of the aryl moiety in high yield improved the overall yield of the process.
