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Biomedical subjects

E Minker

Publications and source records attributed to E Minker.

At least 19 recordsLinked to original sources
PubMed1997

Experimental studies on the antitussive properties of the new xanthine derivative 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]. 1st communication: in vivo demonstration of the effects on animal models of cough and of mucociliary clearance.

CH-13584 (formerly: KHL-8425, 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl], CAS 115779-20-9) is a new xanthine derivative synthesized with the purpose to develop a highly safe compound against several pulmonary disorders, especially for the treatment of acute and chronic cough. CH-13584 showed acute and chronic antitussive activity on citric acid spray-evoked cough model in guinea-pig. CH-13584 was also effective on capsaicine spray and mechanical irritation-induced cough in guinea-pig and rabbit, respectively. The effectivity of CH-13584 on antitussive tests reached and in some cases even exceeded the effectivity of the reference compounds. The compound increased the mucociliary clearance at lower doses than bromhexine.

Animals↗
PubMed1995

[Effects of calcium channel blockers on electrical and mechanical responses of rat phrenic nerve-diaphragm preparations].

The effects of diltiazem, prenylamine and verapamil on the electrical and mechanical responses of a rat phrenic nerve-diaphragm preparation were investigated as a function of the indirect stimulating frequency. The amplitude of the muscle compound action potential was depressed by all three drugs with stimulation between 3 and 50 Hz. The contractile force of the diaphragm was increased by these drugs in concentrations of 3 x 10(-8)-3 x 10(-5) mol/l at low frequency (3-10 Hz), but the contractility was decreased at higher concentrations (above 3 x 10(-5) mol/l). In contrast, a facilitating effect was not observed at a higher stimulating frequency (above 20 Hz), but a concentration depressant effect did develop above 1 x 10(-6) mol/l. The literature data and our results suggest that low concentrations of calcium channel blocking agents can not influence the trigger calcium current at low frequency (under 15 Hz), but calcium liberation and the contractile force are increased by these drugs. The intracellular calcium liberation triggered by the calcium current or the muscle force was inhibited by these drugs at higher concentrations. Above 15 Hz, the liberated intracellular calcium is insufficient for the contraction, so an adequate quantity of calcium is obtained from the extracellular space. It is suggested that an adequate calcium uptake is inhibited at low concentrations of these drugs at higher frequency, and the contractility is thereby inhibited.

Animals↗
PubMed1995

Experimental study on the kinetics of mucociliary activity in rabbit airways.

Noninvasive radioaerosol technique was applied to investigate the mucociliary activity of bronchial mucosa using 99mTc-labelled homologous erythrocytes for inhalation. Radioactivity was continuously measured for 60 min with a gamma camera connected online to the computer. Time-activity kinetic parameters were calculated by a monoexponential model. Test substance azelastine and bromhexine were used to demonstrate the validity of experimental method discussed.

Administration, Inhalation↗
PubMed1993

Influence of chinoin-170, a novel antitussive, on the mucociliary activity in respiratory airways of rats, rabbits, guinea-pigs and man.

Chinoin-170 (Ch-170; 3,7-dihydro-1,3-dimethyl-7-[(5-methyl-1,2,4- oxadiazol-3-yl)methyl]1H-purine-2,6-dione) is a new antitussive with bronchodilating activity. Its effects on the ciliary beating frequency (CBF) and mucociliary clearance were studied. In tracheal explants of rats, Ch-170 dose-dependently at concentrations 2 and 5 mg mL-1 depressed CBF by 24 and 33%, respectively. In human mucosal explants, however, no effects were seen at concentrations up to 5 mg mL-1. In anaesthetized guinea-pigs, an intravenous 50 mg kg-1 dose of Ch-170 caused no changes, and 100 mg kg-1 increased the CBF by 15%. Intravenous Ch-170 dose-dependently increased by 93 (50 mg kg-1), 179 (70 mg kg-1) and 253% (100 mg kg-1) the tracheobronchial mucociliary clearance in rabbits. The effect, studied using 99mTc-labelled red blood cells as a marker, was of similar quantity to that brought about by administering 16, 25 and 40 mg kg-1 doses of bromhexine. It is concluded that unlike many older antitussives, Ch-170 in-vitro only slightly decreases the CBF in rats and has no adverse effects on the CBF in human mucosal explants at concentrations up to 5 mg mL-1. In-vivo, Ch-170 does not significantly alter the CBF in guinea-pigs, but dose-dependently increases the mucociliary clearance in rabbits. The increase is most probably a result of changes in the production and the properties of respiratory mucus.

Animals↗
PubMed1993

The pharmacological reactivity of an isolated circular smooth muscle strip of the rabbit common bile duct.

An in vitro isolated spiral strip of rabbit common bile duct was prepared and tested for its pharmacological reactivity. It was found to be a suitable preparation with a long lasting and stable sensitivity when exposed to various drugs. The pharmacological reactivity proved to vary along the common bile duct; the different portions (sphincteric, median and hepatic) displayed different activities to the various agonists and antagonists. The following receptors were identified in different sections: alpha and beta-adrenergic, muscarinic cholinergic, bradykinin, H1 and prostaglandin F2 alpha. Only the sphinteric portion exhibited rhythmic peristalsis; the other portions produced merely small, irregular spontaneous contractions.

Adrenergic alpha-Agonists↗
PubMed1992

Influence of azelastine and some selected drugs on mucociliary clearance.

The effect of azelastine and some selected compounds on ciliary beating frequency (CBF) was investigated in vitro using human mucosal samples and in vivo using anesthetized guinea pigs. Further influence of azelastine on mucus secretion was evaluated in mice and on mucociliary clearance in anesthetized rabbits. Azelastine influenced the ciliary beating frequency neither in vitro nor in vivo. Azelastine, similarly to salbutamol, ambroxol, and bromhexine, increased mucus secretion measured by the tracheal output of phenol red. Azelastine dose-dependently enhanced mucociliary clearance measured by elimination of 99mTc-labeled erythrocytes in rabbits. The activity of azelastine proved to be about 10 times stronger than that of bromhexine. Since the ciliary activity remained unchanged under the influence of azelastine, it is likely that azelastine increases the mucociliary clearance by enhancing bronchial secretion. It is possible that the observed increase in mucociliary clearance may contribute to the beneficial effect of azelastine in the treatment of respiratory diseases.

Animals↗
PubMed1991

Azelastine: a multifaceted drug for asthma therapy.

Azelastine (4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-p hthalazinone hydrochloride), a novel long-acting antiasthmatic/antiallergic drug has been demonstrated to be effective in the treatment both of asthma and of allergic rhinitis. In this paper some selected properties of azelastine are presented which might contribute to its antiasthmatic and antiallergic effect. Azelastine causes a marked inhibition of generation of oxygen radicals in alveolar macrophages. A bronchosecretolytic activity of azelastine is observed which is based on the secretion of a more liquid mucus. Furthermore, the mucociliary clearance is enhanced as demonstrated in a rabbit model. Also IL-1 generation is inhibited in vitro and in vivo. Finally, the possible tissue and cellular accumulation of azelastine in lung and alveolar macrophages resp. is discussed.

Animals↗
PubMed1991

Experimental and clinicopharmacological study of rectal absorption of chloroquine.

Chloroquine administered as a rectal suppository is resorbed both in rabbits and human volunteers. Although the chloroquine blood level in rabbit is proportional to the dose investigated, the human rectal mucosa has a limited absorption capacity of chloroquine being saturated at 15 mg/kg dose. In spite of this saturation character the chloroquine applied as rectal suppository may be a suitable formulation to treat or prevent the malarial infection for persons unable to take the drug perorally, e.g. children, or unconscious adults, or persons suffering with GI complaints after swallowing the chloroquine tablet.

Administration, Rectal↗
PubMed1986

Effect of muscle relaxants on the motor endplate of diabetic and glucocorticoid pretreated rats.

The susceptibility to d-tubocurarine, gallamine, pancuronium, succinylcholine, and decamethonium of the motor endplate innervated by the anterior tibial nerve was studied in alloxan diabetic rats and in rats pretreated with cortisone and dexamethasone. The sensitivity to various muscle relaxants of cholinergic receptors in the motor endplate of alloxan diabetic and glucocorticoid-treated rats was changed. Beside alterations in affinity, in some cases the kinetics of action were also altered as compared to controls. The phenomenon is suggested to be brought about by a modulator substance circulating in the blood of alloxan diabetic and glucocorticoid-treated rats.

Alloxan↗
PubMed1984

Alpha-bungarotoxin selectively inhibits stimulus-bound repetition in isolated frog sympathetic ganglion.

In the isolated frog sympathetic ganglion incubation with alpha-BTx until the steady state irreversibly inhibited synaptic transmission, furthermore, similarly to d-TC it selectively prevented stimulus-bound repetition (SBR) elicited by neostigmine. This finding showed that alpha-BTx binds nACh receptors were involved in the synaptic transmission and in the generation of SBR. Its binding was prevented by preincubation of the ganglia with cholinergic agonists and antagonists (receptor protection). Since alpha-BTx specifically binds only to C10-type nACh receptors, but not to C6-type nACh receptors, our results suggest that, in contrast to the mammalian and avian sympathetic ganglia, mostly C10-type nACh receptors are present in the frog sympathetic ganglia. The ability of the frog ganglion to generate SBR, furthermore, its selective inhibition by alpha-BTx may be explained by the presence of C10-type nACh receptors.

Action Potentials↗
PubMed1984

A study of the origin of altered pharmacological reactivity of synaptic structures caused by diabetes and pretreatment with contrainsular agents.

The effect of membrane-stabilizing ganglionic blocking agents was found to be decreased in the ganglia of diabetic cats. Similarly, the sensitivity to membrane-stabilizing muscle relaxants of motor endplates in diabetic rats was also diminished, while the effectivity of depolarizing agents was augmented. Analysing the mechanism of action of these phenomena, it was shown that in diabetes developing as a result of pancreas removal or contrainsular treatment, a factor appeared in the blood of the experimental animals which was heat labile and facilitated the transmission process in the cholinergic synapses. In higher concentration, it produced ganglionic excitation and muscle twitching. This factor influenced the effect of drugs acting at the ganglionc synapses and motor endplates.

Animals↗
PubMed1983

Insulin-induced factors derived from lymph node cells influence anaphylactoid reaction in the rat.

The effect of supernatants of isolated lymph node cells exposed to insulin has been studied on the anaphylactoid reaction induced by dextran in the rat paw. Native supernatants derived from rat lymphocytes were shown to increase dextran response only from April to October, while in the intermediate period no potentiation was obtained. The supernatants were filtered through sephadex G-25, G-50, and G-100 gels. Pro-inflammatory activity was recovered in the void volume of sephadex G-25 or G-50 columns, while it ran with bovine serum albumin marker suggesting an approximate mol. wt. of 70-kilodalton. Potentiation was detectable in adrenalectomized rats from November through April. A fraction of the eluate recovered from sephadex G-25 gels in the range of 1- to 6-kilodalton was found to suppress dextran edema. Supernatants of calf lymph node cells with insulin were fractionated on DEAE-sephadex A-50 and yielded two distinct fractions, one with pro-inflammatory and the other with anti-inflammatory effect. These results suggest that insulin affects anaphylactoid reaction via the release of some lymphocyte mediators.

Anaphylaxis↗
PubMed1983

Neurogenic component in the effect of papaverine, drotaverine and bencyclane.

Papaverine, drotaverine and bencyclane, drugs considered to have direct action on the smooth muscle, inhibited synaptic transmission in the isolated a sympathetic ganglion of the frog. Their effect depended upon the concentration applied. The ganglionic blocking effect of papaverine and drotaverine in the concentration range from 10(-8) to 10(-6) mol/l was partially antagonized by naloxone and nalorphine as well as by increasing the Ca2+ concentration in the incubation medium. This refers to an activation of specific opiate receptors in the mechanism of ganglionic action of these drugs. The ganglionic effect of bencyclane may be due to its local anaesthetic property, since it was prevented by neither naloxone nor nalorphine, and an increase in the Ca2+ concentration in the medium had no influence on it.

Animals↗
PubMed1983

[Synthesis, conformation and pharmacological effect of some stereoisomeric condensed 1,3-oxazine-4-ones. 44: Stereochemical studies; 22: Saturated heterocycles].

It has been reported the synthesis, examination of the stereochemistry and biological effect of 2-substituted-cis-5,6-trimethylen-, cis- and trans-5,6-tetramethylene and -5,6-pentamethylene-2,3,5,6-tetrahydro-1,3-oxazine-4-one derivatives. Primarily cis-isomers were synthetized because in the pharmacological test systems the trans isomers were less active. The compounds tested have an antiphlogistic effect of different intrinsic activity.

Animals↗
PubMed1981

Inhibition of ganglionic transmission by narcotic analgesics; an effect antagonized by naloxone, nalorphine and calcium.

Methadone, azidomorphine, oxycodone and fentanyl inhibit synaptic transmission in isolated sympathetic ganglia of the frog and rat, just as did morphine and pethidine in our previous investigations. This inhibitory effect can be antagonized not only by naloxone and nalorphine but also by increasing calcium concentration of the perfusion fluid of the ganglia. The inhibitory effect on transmission of narcotic analgesics takes place on specific opiate receptors of the peripheral ganglia.

Analgesics, Opioid↗
PubMed1981

Pharmacological responses by different portions of guinea pig vas deferens circular muscle preparation.

The different segments of the guinea pig vas deferens circular muscle exhibit differential response patterns upon pharmacological stimulation. Namely, apart from barium chloride, the affinity and intrinsic activity of certain agonists and the strength of maximum contractions they induce appear to decrease along the path from the epididymis toward the prostate. If one subdivides the vas deferens into 3 parts of equal length such as epididymal, medial and prostatic portions, then adrenaline, acetylcholine, acetyl-beta-methylcholine, dopamine, histamine and bradykinin induce contractions on each of the 3 parts; whereas tyramine, ephedrine elicit responses in the epididymal and medial portions; amphetamine, DMPP, serotonin and PGF2 alpha in turn provoking contractions exclusively on the epididymal portion. The effects of adrenaline and noradrenaline are blocked by phentolamine and tolazoline; the responses to acetylcholine, acetyl-beta-methylcholine and carbamyl-beta-methylcholine are antagonized by atropine over a specific concentration range. The effects of tyramine, ephedrine and amphetamine are inhibited by phentolamine in an remarkably low dose range (pA2 = 13.51 +/- 0.09; 14.54 +/- 0.31; 14.35 +/- 0.12). The situation was the same when tyramine-dibenamine and tyramine-phenoxybenzamine combinations were tested (pD'2 = 14.03 +/- 0.37; 13.26 +/- 0.03). Based on these findings the presence of a peculiar alpha adrenergic receptor is suggested on the sympathetic postganglionic fibres. In addition to the already identified alpha adrenergic, muscarinic cholinergic and histamine H1 receptors, we could show the presence of dopaminergic receptors too in the vas deferens circular muscle.

Acetylcholine↗