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Biomedical subjects

D Staneva-Stoytcheva

Publications and source records attributed to D Staneva-Stoytcheva.

At least 37 records · Page 2Linked to original sources
PubMed1991

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. On single application nifedipine exerted a different effect on the phenobarbital- or beta-naphthoflavone-provoked enzyme induction. The phenobarbital-induced BND activity and the cytochrome P-450 content were not changed, while the beta-naphthoflavone-induced EROD activity and cytochrome P-450 and cytochrome b5 content decreased, the ECOD activity remaining unchanged. Nifedipine administered for three days significantly increased the BND activity and the cytochrome P-450 content. The three-day administration of nifedipine plus phenobarbital resulted in a further increase in the BND activity and the cytochrome P-450 content. Consistent with this finding was the potentiation of the phenobarbital-induced shortening of hexobarbital sleep. Nifedipine administered at a single dose, one hour before beta-naphthoflavone had no effect per se but potentiated the enzyme-inducing effect of beta-naphthoflavone on the EROD activity and the cytochrome P-450 content but not on the ECOD activity. These data could be taken into account when considering the possible interactions between nifedipine and other drugs applied at different sequence and duration.

Animals↗
PubMed1991

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. for five days administered alone or together with digoxin). The calculated elimination half-life(t1/2) and the area under the curve (AUC) of digoxin were increased and the digoxin clearance was decreased, being most pronounced in animals receiving a combination of amiodarone and digoxin for five days. Changes were observed neither in the digoxin toxicity in amiodarone-treated guinea-pigs nor in the serum levels of T4, T3 and TTH. The possible mechanisms of the digoxin-amiodarone interactions are discussed.

Amiodarone↗
PubMed1990

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. A significant reduction in the number (Bmax) of binding sites for [3H]DHA was established after the 3 Ca2(+)-antagonists as well as after TFP. 3. No changes in the affinity values (Kd) [3H]DHA binding were found in all treated groups. 4. The fluidity characteristics of the cerebral cortex membranes in nifedipine- and flunarizine-treated rats did not differ from those in controls. 5. Based on these results, we concluded that long-term treatment with Ca2(+)- and calmodulin-antagonists might induce changes in the central adrenergic mechanisms.

Animals↗
PubMed1990

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. The [3H]QNB binding capacity (Bmax) was decreased by three Ca2(+)-antagonists: nifedipine, verapamil and flunarizine, the decrease was most pronounced with nifedipine. 3. The decrease in the number of muscarinic receptors after nifedipine and flunarizine was accompanied by an increase in their affinity; verapamil decreased both the number and the affinity of muscarinic receptors. 4. The calmodulin antagonist trifluoperazine changed neither the number nor the affinity of muscarinic receptors. 5. It is suggested that continuous treatment with different Ca2+ or calmodulin antagonists leads to difference in character and degree of alterations in the basic characteristics of muscarinic receptors in rat cerebral cortex.

Animals↗
PubMed1990

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. The cells were exposed to farmarubicin, ryodipine and combination of both drugs. The results obtained clearly demonstrated that a nontoxic concentration (0.5 microgram/ml) of ryodipine increased (about 5 times) farmarubicin cytotoxicity as the IC50 of the cytostatic was shifted from 1,86 ng/ml on single treatment to 0.37 ng/ml on combined treatment of the cells. The data presented suggest a role for ryodipine in the enhancement of the antitumor activity of some cytostaticts.

Calcium Channel Blockers↗
PubMed1989

Effects of some beta-adrenoceptor blockers on avoidance learning in rats.

In experiments on male Wistar rats, we studied the effects of some beta-adrenoceptor blockers: nonselective-propranolol, pindolol and 3b (a new aminotetraline derivative); and cardioselective (beta 1)-acebutolol and talinolol, on avoidance learning. The nonselective beta-adrenoceptor blockers failed to deteriorate and in some cases even facilitated learning, estimated by the number of avoidance responses and their latencies, while the cardioselective blockers significantly impaired learning process. A significant learning-impairing effect was shown by the beta 2-adrenoceptor agonist salbutamol. Similar was the effect of the mixed alpha- and beta-adrenoceptor blocker labetalol. The results are interpreted in connection with the functional role of beta 1- and beta 2- adrenoceptors in the CNS and with the importance of their balance for learning process.

Adrenergic alpha-Antagonists↗
PubMed1989

Effect of beta-adrenergic and serotoninergic agents on the stress-induced behaviour of "learned helplessness" in rats.

The phenomenon of "learned helplessness" is characterized by elements of motor, cognitive and emotional deficit, and it is particularly suitable to be used as a "model" of behavioural depression. There is no doubt about the central role of the cerebral noradrenaline and serotonin in the stress-induced behavioural deficit. The effects of two known beta-adrenoceptor agonists--salbutamol and trimetoquinol--and the beta-adrenergic blockers propranolol and compound 3B, with beta-blocking activity equipotent to that of propranolol, were investigated under conditions of "prophylactic" and "therapeutic" administration in rats subjected to stress by modelling of the behaviour of learned helplessness. Among the serotoninergic agents, the effects of 5-hydroxytryptophane and of the inhibitor of serotonin synthesis, parachlorophenylalanine, were studied. The experimental results show a favourable effect on the behavioural deficit, caused by the blocking of the adrenergic transmitter system and by increasing the activity of the serotoninergic system.

Adrenergic beta-Agonists↗
PubMed1989

Comparative evaluation of the Ca2+-antagonistic activity of some Bulgarian vasodilating agents and of known Ca2+-antagonists on K+-depolarized smooth muscle from guinea-pig taenia coli.

The informative value of the experimental model for inhibition of the effect of the Ca2+-induced contraction in 40 mM K+-depolarized smooth muscle from guinea-pig taenia coli, is investigated in order to determine the intensity of the Ca2+-antagonistic activity of different agents on the voltage-dependent calcium channels. The Ca2+-antagonistic activity of two original Bulgarian vasodilating agents - piperazine derivatives (aligeron and P-11) possessing potential Ca2+-blocking properties, is compared with the activity of known Ca2+-antagonists which are widely used in clinical practice (verapamil, nitrendipine, cinnarizine and flunarizine). Cumulative dose-response curves of CaCl2 (0.1-3.0 mM) in Ca2+ free K+-depolarizing solution are recorded in advance and 30 min after the administration of the test-substances. On the basis of the intensity of the Ca2+-antagonistic activity, determined by their pA2 values, the substances investigated are ordered as follows: nitrendipine greater than verapamil greater than cinnarizine greater than or equal to flunarizine greater than aligeron greater than P-11. On the background of the CaCl2-induced (1 mM) long-lasting contraction, the substances tested manifest qualitatively different relaxing effects, which suggest different mechanisms of action of the Ca2+ antagonists studied, as well as the significance of the experimental protocol in evaluating the intensity of the Ca2+ antagonistic activity.

Animals↗
PubMed1988

Beta-adrenoblocking activity of a new derivative of 2-aminotetraline based on some metabolic responses in cats and rats.

Previous pharmacological investigations of a newly synthetized derivative of 2-aminotetraline: trans-2-isopropylamino-3-hydroxy-5,8-dimethoxy 1,2,3,4-tetrahydronaphthalene (3b) have shown it to possess a beta-adrenergic blocking activity. In the present work we studied the influence of 3b on some biochemical indices characteristic of beta-adrenergic stimulation: blood levels of glucose, lactate and FFA in cats and rats, and phosphorylase "a" activity in rat myocardium. The dose used (0.5 mg/kg) in rats was the same as the dose of propranolol (0.5 mg/kg). In all experiments on cats and rats compound 3b decreased the effects of isoproterenol on the blood levels of glucose, lactate and FFA and on the phosphorylase "a" activity of the myocardium and this action was comparable with that of propranolol. The similar molecular mass and LD50 of 3b and propranolol allowed quantitative comparisons of the beta-adrenoblocking effects of both drugs in the dose used. The results suggest that compound 3b possesses metabolic effects characteristic of beta-adrenoblocking agents.

Adrenergic beta-Antagonists↗
PubMed1988

Pharmacodynamic effects of a 2-piperazinotetralin (P-11)--combined alpha- and beta-adrenoceptor blocking drug with hypotensive action.

The piperazinotetralin derivative P-11 at hypotensive doses of 0.25 to 1.00 mg/kg i.v. reduced the pressor effects of exogenous noradrenaline (10 micrograms/kg i.v.) in reserpine-pretreated rats, but was ineffective in nonreserpinized normotensive urethane-anesthetized rats. P-11 (0.25 to 1.00 mg/kg i.v.) decreased the positive chronotropic effects of isoprenaline (0.2 micrograms/kg i.v.), but potentiated the isoprenaline-induced hypotension in reserpine-pretreated rats. P-11 (10(-7) to 10(-5)M) did not modify the concentration-effect curves for isoprenaline in carbachol-contracted guinea-pig tracheal strips. The pD2 value of isoprenaline was 5.94 before and 6.35 after P-11. The combined alpha1-postsynaptic antagonist/beta1-blocking activity of this compound is discussed.

2-Naphthylamine↗
PubMed1988

Involvement of peripheral dopaminergic mechanisms in the action of a 2-piperazinotetralin (P-11) with hypotensive activity.

The piperazinotetralin derivative P-11 applied in increasing concentrations (10(-12) to 10(-4)M) inhibited field electrical stimulation-induced contractions of isolated rabbit ear artery and this effect was not reversed by S-sulpiride (10(-6)M). This was probably due to the postsynaptic alpha receptor-blocking action of P-11. The compound also did not modify PGF2 alpha-induced contractions of isolated rabbit renal artery, suggesting the lack of action of P-11 on postsynaptic DA1 receptors. The lack of activity of P-11 on DA1 and DA2 peripheral receptors was associated with the chemical structure of the compound.

2-Naphthylamine↗
PubMed1988

Effect of an original piperazine derivative of tetraline on the adrenergically mediated metabolic responses in cats and rats.

One piperazine derivative of tetraline (with code P11), possessing hypotensive and anti-hypertensive activity, is studied. Its alpha- and beta-adrenoceptor blocking properties are characterized by using indicators of adrenergically mediated metabolic responses in cats and rats. The parameters studied are: glucose and lactate in the blood, free fatty acids in the plasma and the activity of phosphorylase "a" in rat myocardium. The alpha- and beta-adrenergic properties of P11 are characterized by using adrenergic and dopaminergic agonists and antagonists (adrenaline, isoproterenol, phenylephrine, propranolol, phentolamine, apomorphine and pimozide) in the different experimental setups. Compound P11 studied inhibits the effect of phenylephrine on the glucose level in the blood of rats in a definite dose interval (1-4 mg/kg) which suggests that it possesses alpha-adrenoblocking properties. P11 decreases slightly the effects of isoproterenol or does not change these effects on the levels of glucose, lactate and free fatty acids in cats. There are no changes in the effect of adrenaline on the glucose content in rat blood and the isoproterenol-activated phosphorylase in rat myocardium is not inhibited. This gives grounds to assume that P11 possesses slight beta-adrenoblocking properties. From the analysis of the proper hyperglycaemizing action of P11 in rats in the 1-8 mg/kg dose range it may be assumed that dopamine-agonistic mechanisms are involved.

Adrenergic alpha-Antagonists↗
PubMed1988

Influence of the combined chemotherapeutic drug tuboprim on drug metabolism.

Tuboprim (Pharmachim, Bulgaria) is a combined synergistic chemotherapeutic drug, containing rifampicin (Tubocin-Pharmachim) (TB) and trimetoprim (TM). In experiments on rats and mice the influence of single and repeated (4 days) doses of Tuboprim and of the corresponding doses of TB and TM on some drug metabolizing enzyme systems and other factors of drug metabolism was studied. The following indices were investigated: hexobarbital sleeping time (HBST), activities of hexobarbital oxidaze (HBO), aniline hydroxylase (AH), ethylmorphine-N-demethylase (EMND), uridindiphosphoglucuronyl-transferase (UDPGT), NADPH-cytochrome-C reductase and the cytochrome P-450, cytochrome b5 and microsomal protein contents. A single dose of TB (100 mg/kg in rats and 80 mg/kg in mice) inhibited HBO, EMND and AH; TM (30 mg/kg in rats and 20 mg/kg in mice) inhibited HBO and EMND, whereas Tuboprim inhibited EMND only. Repeated (4 days) treatment with TB provoked an induction of HBO, AH, and EMND accompanied by an increase of NADPH-Cyt-C reductase and cytochrome P-450, hem and microsomal protein content. Trimetoprim stimulated EMND only. The combined drug Tuboprim also produced an enzyme induction, but to a considerably less degree than did TB alone. UDPGT activity was not significantly changed.

Animals↗
PubMed1985

Effect of one derivative of 2-aminotetralin on the alpha-adrenergic receptors of isolated vessels.

Experiments were made to test the effects of originally synthesized piperazine derivative of 2-aminotetralin (P11) on the alpha-adrenergic receptors of isolated vessels. Inhibition of the contracting effects of exogenously introduced noradrenaline into isolated rabbit ear artery was found at concentrations of P11 and phentolamine 1 X 10(-8) to 1 X 10(-4) M. IC50 for P11 is 0.68 microM, for phentolamine -- 0,40 microM. There is a certain shift to the right of the concentration effect curves for noradrenaline in isolated strip of rabbit aorta when P11 and phentolamine are applied in concentrations of 1 X 10(-7) to 1 X 10(-5) M. pA2 for P11 is 7.31, for phentolamine -- 8.04. Potentiation of the maximum effect of noradrenaline is observed after P11 1 X 10(-5) M, which decreases upon preliminary administration of cocaine 1 X 10(-5) M and propranolol 1 X 10(-6) M. The tested compound manifests alpha-adrenergic blocking action in the organs studied.

Animals↗
PubMed1985

Changes in the adrenergic reactivity of spontaneously hypertensive rats after abrupt withdrawal of chronic clonidine treatment.

An experimental model of the "withdrawal syndrome" in chronic clonidine treatment is reproduced in spontaneously hypertensive rats (SHR). Medication is withdrawn abruptly after daily oral administration of 100 micrograms/kg clonidine for 12 days or after it has been received with the drinking water in a dose of approximately 250 micrograms/kg daily for 14 days. In the course of the treatment, as well as on the 24th and 48th hour after withdrawal, studies are carried out of the changes in the arterial pressure, heart rate, vascular resistance, the contractions of electrically stimulated m.anococcygeus and vas deferens, as well as some biochemical parameters (noradrenaline content in the brain and myocardium, the level of glucose and free fatty acids in the blood, the activity of phosphorylase "a" in the myocardium). In the course of clonidine treatment there is potentiation of the peripheral noradrenaline effects on the arterial pressure and vascular resistance, increasing hyperglycaemia, reduced noradrenaline content in the brain and myocardium, as well as potentiation of the inhibitory effect of clonidine on the contractions of electrically stimulated m.anococcygeus, as well as potentiation of the isoprenaline responses on the arterial pressure. The isoprenaline effects on electrically stimulated vas deferens, as well as the activity of the stimulated phosphorylase "a", decrease. No sharp increase in the arterial blood pressure was observed upon withdrawal of the clonidine treatment. The reactivity of the peripheral pre- and postsynaptic alpha-adrenergic receptors is intensified (the effects of noradrenaline on the arterial pressure and vascular resistance become even stronger, the noradrenaline content in the brain and myocardium and hyperglycaemia increase, and there is potentiation of the inhibitory effect of clonidine on electrically stimulated m.anococcygeus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of a new 2-piperazinotetralin on alpha-1 and alpha-2 adrenergic receptors in isolated rat vas deferens.

The pharmacological action of a newly synthesized piperazine derivative of 2-aminotetralin (P11) on pre- and postsynaptic alpha-adrenoceptors of isolated rat vas deferens has been investigated. P11 shifted noradrenaline concentration-effect curves to the right. The pA2 value was 5.88 for P11, 5.38 for phentolamine, and 7.73 for prazosin. The maximum effect of the agonist was enhanced by P11 and phentolamine, but this enhancement was less pronounced in the presence of 1 X 10(-5) M cocaine and 1 X 10(-6) M propranolol. 1 X 10(-6) M to 1 X 10(-5) M P11 increased the contractions of a field-stimulated vas deferens and antagonized the effects of clonidine (1 X 10(-9) M on the same preparation. The IC50 values of P11, phentolamine and prazosin were 0.40 microM, 0.03 microM and greater than 10.0 microM, respectively. The results show that P11 possesses alpha 1-and alpha 2-adrenolytic activity. The effect of P11 on these receptors most likely participates in the mechanisms of its hypotensive action.

Animals↗