Changes in rat liver monooxygenase activities after administration of atenolol, nifedipine and diltiazem alone and in combination.

The effects of the Ca2+ antagonists nifedipine (NF) and diltiazem (DL) and of the cardioselective beta 1-adrenergic blocking agent atenolol (AT) on the hexobarbital (HB) sleeping time and on the activity of some liver drug-metabolizing enzyme systems in male Wistar rats were studied. Two hours after single oral administration, atenolol (150 mg/kg) did not change hexobarbital sleeping time, while nifedipine (50 mg/kg) and diltiazem (30 mg/kg) prolonged it by 171.2 and 99.

Combined effect of propranolol with nifedipine or with diltiazem on rat liver monooxygenase activities.

The effects of two Ca2+ antagonists nifedipine (NF) and diltiazem (DL) and of the nonselective beta-adrenergic blocking agent propranolol (PR) on the hexobarbital (HB) sleeping time and on the activity of some liver drug-metabolizing enzyme systems in male Wistar rats were studied. Two h after single oral administration PR (50 mg/kg) did not change HB sleeping time, while NF (50 mg/kg) and DL (30 mg/kg) prolonged it by 171.2 and 99.

In vivo induced desensitization of beta-adrenoceptors in rat lung. Effect of nitrendipine.

The effect of nitrendipine on desensitization of beta-adrenoceptors induced by isoprenaline was investigated using rat lungs. Rats were treated with saline, isoprenaline, nitrendipine, or nitrendipine + isoprenaline. After 7 days of treatment, tracheas were isolated and the dissociation constant (Kb) for the propranolol-beta-receptor complex was determined.

Effects of beta-adrenoceptor blocker pindolol, calcium antagonist verapamil and their combination on retention in step-down- and shuttle-box-trained rats and on brain biogenic monoamines.

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.

Effects of flunarizine and nitrendipine on electroconvulsive shock- and clonidine-induced amnesia.

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.

Effects of the beta-adrenergic blockers propranolol and acebutolol on stress-induced learned helplessness behavior of rats.

The latency time and escape ability of rats with learned helplessness behavior were studied after 1, 6 and 14 days of oral treatment with beta-adrenergic blockers propranolol (1 and 3 mg/kg) and acebutolol (10 and 30 mg/kg). A dose-dependent significant decrease in latency time and increase in number of avoidances was established after single, 6 and 14 days propranolol treatment. The selective beta 1-blocker acebutolol did not change the escape characteristics.

Changes in the contractile responses to carbachol and in the inhibitory effects of verapamil and nitrendipine on isolated smooth muscle preparations from rats subchronically exposed to Pb2+ and Zn2+.

Male Wistar rats were exposed to Pb2+ or Zn2+ and to Pb2+ + Zn2+, receiving Pb(CH3COO)2 or/and ZnSO4 with drinking water for 30 days. Cumulative concentration-effect curves for carbachol were obtained in ileum and trachea isolated from control and heavy metal-treated rats. The effect of the Ca2+ channel blockers on the carbachol-induced contractions was studied by addition of increasing concentrations of verapamil or nitrendipine to the bath solution 20 min.

Effects of cobalt or nickel on the sympathetically mediated contractile responses in rat-isolated vas deferens.

Subchronic (30 days) exposure of rats to Co(NO3)2 or NiSO4 (20 mg.kg-1) in drinking water caused suppression of the isolated vas deferens contractile responses to exogenous adenosine 5'-triphosphate (ATP), noradrenaline, and l-phenylephrine, shifting the concentration-response curves to the relevant agonist to the right. Both metals facilitated the alpha 1-adrenoceptor antagonistic effects of prazosin, which resulted in increased pA2 values for the drug (9.

Changes in the contractile responses to carbachol and in the inhibitory effects of verapamil and nitrendipine on isolated smooth muscle preparations from rats subchronically exposed to Co2+ and Ni2+.

Male Wistar rats were exposed to subtoxic doses of Co2+ or Ni2+, receiving Co(NO3)2 or NiSO4 with drinking water for 30 days. No significant differences in the body weight and no visible changes in the behaviour of the controls and experimental animals were established. Cumulative concentration-effect curves for carbachol were obtained in ileum and trachea isolated from control and Co(2+)- or Ni(2+)-treated rats.

Effects of subchronic exposure of rats to lead or zinc on alpha-adrenoceptor-mediated contractile responses in isolated vas deferens.

The effects of subchronic (30 days) drinking water exposure of rats to ZnSO4 or Pb(CH3COO)2 alone or in combination on the adrenergically-mediated contractile responses of isolated vas deferens were studied. The contractile effects of the alpha 1, alpha 2-adrenoceptor agonist noradrenaline (NA) and to the alpha 1-adrenoceptor agonist 1-phenylephrine (1-PhE) were decreased after zinc exposure, whereas after lead exposure or lead plus zinc exposure they were not changed. The contractile responses to field electrical stimulation (FES, 0.

Interactions between the effects of endothelin-1, clonidine and yohimbine on electrically-induced contractions in rat vas deferens.

1. The relationship between endothelin-1(ET-1)-induced effects on the contractile responses of epididymal portion of rat vas deferens elicited by field electrical stimulation (FES: 80 V, 1 msec, 0.1 Hz) and the effects of the alpha 2-adrenoceptor agonist clonidine and the alpha 2-adrenoceptor antagonist yohimbine were studied.

Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals.

Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s.c.

Effects of the calcium antagonists diltiazem, verapamil and nitrendipine on the contractile responses of guinea-pig isolated ileum to electrical stimulation or carbachol.

The effects of the organic Ca2+ antagonists nitrendipine, verapamil and diltiazem on the cholinergic contractile responses induced by field electrical stimulation or carbachol (0.1 microM) and on contractions evoked by high concentration KCl (30 mM) were studied in isolated preparations from the guinea-pig ileum. The three Ca2+ antagonists dose-dependently suppressed the contractile responses showing the same order of potency (nitrendipine greater than verapamil greater than diltiazem) with the three different types of stimulation.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha t1/2 beta, AUC, C1) were found in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. The most pronounced changes were those in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.

Long-term treatment with different calcium- and calmodulin-antagonists induces changes in rat brain alpha-adrenoceptors.

1. The binding characteristics (Bmax and Kd) of the alpha-adrenoceptor radioligand [3H] WB4101 in crude membrane fraction (fraction P2) from cerebral cortex were studied after 13-day oral treatment of male Wistar rats with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin-antagonist trifluoperazine (TFP) (3 mg/kg). 2.

Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals.

Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s. c.

Involvement of calcium ions in the modulation of electrically-induced rat vas deferens contractions by histaminergic drugs.

1. The modulatory action of histaminergic drugs: histamine; 2-(2-aminoethyl)thiazole (H1-agonist); dimaprit (H2-agonist); diphenhydramine (H1-receptor antagonist); and cimetidine (H2-receptor antagonist) on rat vas deferens contractions induced by electrical field stimulation (0.1 Hz, 1 pulse, 1 msec duration, supramaximal voltage) was studied either at different calcium concentrations in the nutrient fluid or after verapamil.

Effect of nifedipine on the enzyme-inducing activity of phenobarbital and beta-naphthoflavone.

Studies were made of the effect of nifedipine on the enzyme-inducing activity of phenobarbital and beta-naphthoflavone estimated by hexobarbital sleeping time, benzphetamine-N-demethylase (BND), ethoxycumarin-O-deethylase (ECOD) and ethoxyresorufin-O-deethylase. (EROD) activity, as well as by the cytochrome P-450 and cytochrome b5 content. Nifedipine at the dose used (100 mg/kg, orally) prolonged hexobarbital sleeping time and affected neither the BND, ECOD and EROD activity, nor the cytochrome P-450 and cytochrome b5 content.

The long-term treatment with the Ca(2+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine decreases the activity of 5-HT1 receptors in rat cerebral cortex and hippocampus.

1. The binding activity of 5-HT1 receptors was studied in membrane fractions from the cerebral cortex and hippocampus of male Wistar rats treated orally for 13 days with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg) and flunarizine (10 mg/kg) and with the calmodulin antagonist trifluoperazine (3 mg/kg). 2.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha, t1/2 beta, AUC, AL) were established in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. Most pronounced were the changes in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.

Changes in benzodiazepine receptors of rat brain after long-term treatment with the Ca(2+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine.

1. The binding of [3H]flunitrazepam to benzodiazepine receptors in the cerebral cortex and hippocampus (membrane fraction P2) was studied after 13-day oral treatment of male Wistar rats with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin (CaM)-antagonist trifluoperazine (TFP) (3 mg/kg). 2.

Do H3-receptors participate in the effects of histamine on electrically-evoked contractions of rat vas deferens?

1. The specific effects of histamine were studied on rat vas deferens contractions induced by electrical field stimulation (0.1 Hz, 1 pulse, 1 msec duration, supramaximal voltage).

Effects of the Ca2(+)-antagonists nifedipine, verapamil, flunarizine and of the calmodulin antagonist trifluoperazine on muscarinic cholinergic receptors in rat cerebral cortex.

1. Studies were made of [3H]QNB binding to muscarinic receptors in a membrane fraction from the cerebral cortex of rats treated orally for 13 days with the Ca2(+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin antagonist trifluoperazine (3 mg/kg). 2.

Ryodipine-induced enhancement of farmarubicin cytotoxicity against human leukemia cells in vitro.

Ryodipine is a recently developed dihydropyridine calcium channel blocker, chemically similar to nifedipine but with some advantages: light stability, low toxicity, etc. In recent years calcium antagonists have attracted attention not only with their cardiovascular activity but also as drugs increasing the antitumor effect of some cytostatics. In the present work the potentiating effect of ryodipine on the farmarubicin-induced cytotoxicity against K 562 human leukemia cells in vitro was evaluated.

Influence of long-term treatment with the Ca2(+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine on beta-adrenoceptors in rat cerebral cortex.

1. The binding of [3H] dihydroalprenolol ((3H]DHA) to beta-adrenoceptors in cerebral cortex membranes (fraction P2) was studied after 13-day oral treatment of male Wistar rats with the Ca2(+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin (CaM)-antagonist trifluoperazine (TFP) (3 mg/kg). 2.