Pharmacological research : the official journal of the Italian Pharmacological Society
-
The ATPase activity of Na,K-ATPase-enriched membranes from canine renal medulla was determined in the absence of local anesthetic and in the presence of procaine, chloroprocaine, bupivacaine, mepivacaine, lidocaine, and two quaternary derivatives of lidocaine (QX-222 and QX-314) at 37( composite function)C. Chloroprocaine (IC(50)= 13 mM) had slightly greater potency than procaine (IC(50)= 17.7 mM). ⋯ QX-222 (IC(50)> 600 mM) and QX-314 (IC(50)= 132 mM) had less potency than lidocaine (IC(50)= 30.4 mM). This study supports the interpretation that the uncharged forms of local anesthetics are much more potent inhibitors of Na,K-ATPase activity than the cationic forms.
-
Cardiac arrhythmia can be a serious complication during general anaesthesia of patients suffering from cardiac arrhythmias and using antiarrhythmic drugs. The aim of the present experiments was to establish the way in which lidocaine and verapamil influence haemodynamic parameters of rabbits after midazolam anaesthesia. The experiments were performed on rabbits. ⋯ Combined administration of midazolam and lidocaine decreased the influence of both midazolam and lidocaine on the total peripheral resistance. An injection of midazolam with verapamil resulted in a significant decrease of blood pressure. Combined administration of midazolam and verapamil caused a significant decrease of heart rate as compared with the initial value and administration of midazolam alone.
-
Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. ⋯ Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.
-
Antinociception, disturbances of motor coordination and development of tolerance to these effects were examined following acute and chronic administration of ACEA-1416, a NMDA receptor/glycine site antagonist, in Swiss Webster mice using the formalin and rotarod tests. In the formalin test, mice were injected with either the vehicle (Tris, 0.05 M) or ACEA-1416 (1-10 mg kg-1). Fifteen or 60 min later, mice were injected with formalin and observed for nociceptive responses (licking and/or biting of the injected paw). ⋯ Tolerance also developed to the motor impairing effect of the drug. Taken together, these data suggest that chronic inhibition of NMDA receptors by ACEA-1416 differentially affected the antinociceptive effect of the drug in the early and late phase of the formalin test. Furthermore, the antinociceptive and motor impairing effects of the drug can be separated.
-
Kindling represents an accepted model of human epileptogenesis. Furthermore, it has been demonstrated that kindled rats show a diminished learning performance in an active avoidance task. In our study we administered different nootropic drugs to kindled rats to test their effects on learning a two-way active avoidance task in the shuttle-box. ⋯ Meclofenoxate injected prior to the kindling stimulation was ineffective, whereas administration prior to the learning test improved the learning performance effectively. A complementary action was shown in experiments with vinpocetine. Only piracetam prevented the occurrence of kindling-induced learning deficits regardless the administration schedule.