Résumé
Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.
Sujets)
Animaux , Clonidine/antagonistes et inhibiteurs , Interactions médicamenteuses , Femelle , Hypnotiques et sédatifs/pharmacologie , Mâle , Souris , Nifédipine/pharmacologie , Propranolol/pharmacologie , Réserpine/antagonistes et inhibiteursSujets)
Analgésie , Animaux , Appétit/effets des médicaments et des substances chimiques , Pression sanguine/effets des médicaments et des substances chimiques , Chats , Système nerveux central/effets des médicaments et des substances chimiques , Stimulants du système nerveux central/pharmacologie , Diurèse/effets des médicaments et des substances chimiques , Chiens , Femelle , Cochons d'Inde , Mâle , Souris , Contraction musculaire/effets des médicaments et des substances chimiques , Contraction myocardique/effets des médicaments et des substances chimiques , Pentobarbital/antagonistes et inhibiteurs , Pipérazines/pharmacologie , Lapins , Rats , Réflexe/effets des médicaments et des substances chimiques , Réserpine/antagonistes et inhibiteurs , Transmission synaptique/effets des médicaments et des substances chimiques , Contraction utérine/effets des médicaments et des substances chimiquesRésumé
In rats, propranolol potentiated alcohol and pentobarbitone hypnosis, but not barbital sleeping time, indicating enzyme inhibition as a possible mechanism of potentiation. Propranolol showed anticonvulsant effect on normal and reserpine treated rats by MES test, but showed dose related lowering of MET. Probable mechanisms are discussed.