Benzodiazepine receptor affinities, behavioral, and anticonvulsant activity of 2-aryl-2,5-dihydropyridazino[4,3-b]indol- 3(3H)-ones in mice
| Autor: | Pietro Giusti, Cristina Rettore, Francesco Campagna, Milena Rizzo, Fausta Palluotto, Umberto Falconi, Angelo Carotti, Giovambattista De Sarro, Angela De Sarro, Ruth M. McKernan |
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| Rok vydání: | 2000 |
| Předmět: |
Flumazenil
Male Indoles medicine.drug_class medicine.medical_treatment Clinical Biochemistry Pharmacology Motor Activity Toxicology Biochemistry Body Temperature Behavioral Neuroscience chemistry.chemical_compound Epilepsy Benzodiazepines Mice Seizures DMCM medicine Animals Hypnotics and Sedatives Receptor Biological Psychiatry Benzodiazepine Behavior Animal Antagonist Ketones medicine.disease Receptors GABA-A Abecarnil Anticonvulsant chemistry Anti-Anxiety Agents Mice Inbred DBA Pyrazoles Anticonvulsants medicine.drug Synaptosomes |
| Zdroj: | Pharmacology, biochemistry, and behavior. 65(3) |
| ISSN: | 0091-3057 |
| Popis: | The anticonvulsant properties of 1,4-benzodiazepines (BDZs), pyrazoloquinolones (CGS), 2-aryl-2,5-dihydropyridazino[4, 3-b]indol-3(3H)-ones (PIs) 1 1i 1d 1f 1e 1b 1c 1h, and 1a, the latter being inactive against audiogenic seizures. Some PIs 1 and abecarnil showed anticonvulsant properties against seizures induced by PTZ with a potency lower than that observed in audiogenic seizures. The pharmacological actions of 1d, 1f, and 1i were significantly reduced by a treatment with flumazenil (8.24 micromol/kg IP), suggesting a clear involvement of benzodiazepine mechanisms in the anticonvulsant activity of these compounds or their metabolites. The anticonvulsant activity of 1d, 1f, and 1i was also evaluated against seizures induced by two beta-carbolines namely methyl-beta-carboline-3-carboxylate (beta-CCM) and methyl-6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), in DBA/2 mice: they gave better protection against seizures induced by beta-CCM than the ones by DMCM. The potency of various BDZs and PIs as inhibitors of specific [3H]flumazenil binding to neuronal membranes, was also evaluated. The radioligand binding study, carried out on stable cell lines expressing definite combinations of benzodiazepine receptor subunits, demonstrated that 1b, 1e, 1d, and 1h have preferential interaction with alpha(1), beta(3), gamma(2), receptor subtypes. |
| Databáze: | OpenAIRE |
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