RESUMO
This study was designed to examine the calcium channel blockers flunarizine and nitrendipine for their ability to prevent electroconvulsive shock (ECS)- or clonidine-induced deterioration of the inhibitory avoidance performance (step-down) in rats. Flunarizine (10 mg/kg) and nitrendipine (40 mg/kg) were found to prevent the ECS- or clonidine-provoked amnesia after oral administration for 12 days. The mechanisms of action of the two drugs are considered. The results of this study further suggest that calcium antagonists might be useful in the treatment of cognitive disorders.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Flunarizina/farmacologia , Memória/efeitos dos fármacos , Nitrendipino/farmacologia , Agonistas alfa-Adrenérgicos/toxicidade , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Clonidina/toxicidade , Eletrochoque/efeitos adversos , Masculino , Memória/fisiologia , Ratos , Ratos WistarRESUMO
The effects of the beta-adrenoceptor blocker pindolol and the calcium antagonist verapamil administered alone or in combination on retention in step-down- and shuttle-box-trained rats and on the biogenic monoamine levels in the frontal cortex and hippocampus were examined. The chronic oral treatment with pindolol impaired retention in step-down- and shuttle-box-trained rats, decreasing the dopamine (DA) and noradrenaline (NA) levels and increasing the serotonin (5-HT) levels in the cortex and hippocampus. Verapamil did not influence retention in step-down- and shuttle-box avoidance situation and the biogenic monoamine levels in the frontal cortex and hippocampus. It should, however, be noted that the chronic oral treatment with verapamil completely abolished the retention-impairing effect of pindolol, restoring to normal DA, NA and 5-HT levels. These findings might be of interest to clinical practice and suggest the necessity for using a combination of beta-blockers with Ca2+ antagonists in case of prolonged treatment of cardiovascular diseases.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Monoaminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Memória/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Antagonismo de Drogas , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Norepinefrina/metabolismo , Pindolol/farmacologia , Ratos , Ratos Wistar , Serotonina/metabolismo , Verapamil/farmacologiaRESUMO
The effects of the Ca2+ and 5-HT1 and 5-HT2 receptor antagonist dotarizine and of some other agonists and antagonists of different 5-HT receptor subtypes administered alone or in combination with the 5-HT uptake inhibitor fluoxetine (FLU) on nociception were studied, using a foot-pressure method (analgesy-meter testing). Dotarizine (DOT) administered at a dose of 50 mg/kg for 3 days orally significantly increased the pain threshold. Fluoxetine (FLU) administered at a dose of 10 mg/kg for 3 days also significantly increased the pain threshold. The combination of DOT and FLU abolished the analgesic effects of the two drugs. The 5-HT1A and 5-HT1B/1C receptor agonists buspirone and m-CPP decreased the pain threshold. The antagonists of 5-HT1A(NAN-190),5-HT1/5-HT2(methysergide), 5-HT2 (ritanserin), and 5-HT3 (ondansetron) receptors as well as the agonists of 5-HT2(DOI) and 5-HT3 (mCPBG) receptors increased the pain threshold. Fluoxetine at a single dose of 10 mg/kg differently influenced the effects of the 5-HT agonists and antagonists on nociception. Comparison of the effects of dotarizine with the effects of some of the agonists and antagonists of 5-HT receptor subtypes on the nociceptive and other actions suggests the possibility of a therapeutic value of dotarizine as an antimigraine drug.