Involvement of nitric oxide-cGMP pathway in the anticonvulsant effects of lithium chloride on PTZ-induced seizure in mice
| Autor: | Sara Ebrahimi Nasrabady, Tina Hedayat, Arash Bahremand, Pouya Ziai, Ahmad Reza Dehpour, Reza Rahimian, Borna Payandemehr |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Indazoles Lithium (medication) medicine.drug_class Phosphodiesterase Inhibitors medicine.medical_treatment Convulsants Arginine Nitric Oxide Piperazines Sildenafil Citrate Nitric oxide chemistry.chemical_compound Mice Seizures Internal medicine Convulsion medicine Animals Sulfones Enzyme Inhibitors Cyclic GMP Seizure threshold Dose-Response Relationship Drug Mood stabilizer Effective dose (pharmacology) Methylene Blue Disease Models Animal Anticonvulsant Endocrinology NG-Nitroarginine Methyl Ester Treatment Outcome Neurology chemistry Purines Lithium chloride Pentylenetetrazole Anticonvulsants Neurology (clinical) medicine.symptom Nitric Oxide Synthase Lithium Chloride Injections Intraperitoneal medicine.drug |
| Zdroj: | Epilepsy research. 89(2-3) |
| ISSN: | 1872-6844 |
| Popis: | Lithium is still the mainstay in the treatment of affective disorders as a mood stabilizer. Lithium also shows some anticonvulsant properties. While the underlying mechanisms of action of lithium are not yet exactly understood, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of lithium is mediated via NO-cGMP pathway. Injection of a single effective dose of lithium chloride (25 mg/kg) intraperitoneally (i.p.) increased significantly the seizure threshold (P0.01). The anticonvulsant properties of the effective dose of lithium were prevented by pre-treatment with the per se non-effective doses of L-ARG [the substrate for nitric oxide synthase; NOS] (30 and 50 mg/kg) or sildenafil [a phosphodiesterase 5 inhibitor] (10 and 20 mg/kg). L-NAME [a non-specific NOS inhibitor] (5, 15 and 30 mg/kg), 7-NI [a specific neural NOS inhibitor] (30 and 60 mg/kg) or MB [a guanylyl cyclase inhibitor] (0.5 and 1 mg/kg) augmented the anticonvulsant effect of a sub-effective dose of lithium (10 mg/kg, i.p.). Whereas several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of lithium. Our findings demonstrated that nitric oxide-cyclic GMP pathway could be involved in the anticonvulsant properties of the lithium chloride. In addition, the role of constitutive NOS versus inducible NOS is prominent in this phenomenon. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect